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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
<issn pub-type="epub">1664-3224</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fimmu.2024.1277074</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Immunology</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Garlic bioactive substances and their therapeutic applications for improving human health: a comprehensive review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>El-Saadony</surname><given-names>Mohamed T.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/901699"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Saad</surname><given-names>Ahmed M.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1767382"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Korma</surname><given-names>Sameh A.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1762389"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Salem</surname><given-names>Heba M.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2430205"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/resources/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Abd El-Mageed</surname><given-names>Taia A.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/402425"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Alkafaas</surname><given-names>Samar Sami</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2179278"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Elsalahaty</surname><given-names>Mohamed I.</given-names>
</name>
<xref ref-type="aff" rid="aff8"><sup>8</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2408105"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Elkafas</surname><given-names>Sara Samy</given-names>
</name>
<xref ref-type="aff" rid="aff9"><sup>9</sup></xref>
<xref ref-type="aff" rid="aff10"><sup>10</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mosa</surname><given-names>Walid F. A.</given-names>
</name>
<xref ref-type="aff" rid="aff11"><sup>11</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1938790"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Ahmed</surname><given-names>Ahmed Ezzat</given-names>
</name>
<xref ref-type="aff" rid="aff12"><sup>12</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1828202"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Mathew</surname><given-names>Betty T.</given-names>
</name>
<xref ref-type="aff" rid="aff13"><sup>13</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Albastaki</surname><given-names>Noor A.</given-names>
</name>
<xref ref-type="aff" rid="aff14"><sup>14</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Alkuwaiti</surname><given-names>Aysha A.</given-names>
</name>
<xref ref-type="aff" rid="aff13"><sup>13</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>El-Tarabily</surname><given-names>Marawan K.</given-names>
</name>
<xref ref-type="aff" rid="aff15"><sup>15</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>AbuQamar</surname><given-names>Synan F.</given-names>
</name>
<xref ref-type="aff" rid="aff13"><sup>13</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/377716"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>El-Tarabily</surname><given-names>Khaled A.</given-names>
</name>
<xref ref-type="aff" rid="aff13"><sup>13</sup></xref>
<xref ref-type="aff" rid="aff16"><sup>16</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/408412"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ibrahim</surname><given-names>Salam A.</given-names>
</name>
<xref ref-type="aff" rid="aff17"><sup>17</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/751953"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
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</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University</institution>, <addr-line>Zagazig</addr-line>, <country>Egypt</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Biochemistry, Faculty of Agriculture, Zagazig University</institution>, <addr-line>Zagazig</addr-line>, <country>Egypt</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Food Science, Faculty of Agriculture, Zagazig University</institution>, <addr-line>Zagazig</addr-line>, <country>Egypt</country></aff>
<aff id="aff4"><sup>4</sup><institution>School of Food Science and Engineering, South China University of Technology</institution>, <addr-line>Guangzhou</addr-line>, <country>China</country></aff>
<aff id="aff5"><sup>5</sup><institution>Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University</institution>, <addr-line>Giza</addr-line>, <country>Egypt</country></aff>
<aff id="aff6"><sup>6</sup><institution>Department of Soils and Water, Faculty of Agriculture, Fayoum University</institution>, <addr-line>Fayoum</addr-line>, <country>Egypt</country></aff>
<aff id="aff7"><sup>7</sup><institution>Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University</institution>, <addr-line>Tanta</addr-line>, <country>Egypt</country></aff>
<aff id="aff8"><sup>8</sup><institution>Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University</institution>, <addr-line>Tanta</addr-line>, <country>Egypt</country></aff>
<aff id="aff9"><sup>9</sup><institution>Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University</institution>, <addr-line>Menofia</addr-line>, <country>Egypt</country></aff>
<aff id="aff10"><sup>10</sup><institution>Faculty of Control System and Robotics, Information Technologies, Mechanics and Optics (ITMO) University</institution>, <addr-line>Saint-Petersburg</addr-line>, <country>Russia</country></aff>
<aff id="aff11"><sup>11</sup><institution>Plant Production Department (Horticulture-Pomology), Faculty of Agriculture, Saba Basha, Alexandria University</institution>, <addr-line>Alexandria</addr-line>, <country>Egypt</country></aff>
<aff id="aff12"><sup>12</sup><institution>Biology Department, College of Science, King Khalid University</institution>, <addr-line>Abha</addr-line>, <country>Saudi Arabia</country></aff>
<aff id="aff13"><sup>13</sup><institution>Department of Biology, College of Science, United Arab Emirates University</institution>, <addr-line>Al Ain</addr-line>, <country>United Arab Emirates</country></aff>
<aff id="aff14"><sup>14</sup><institution>Department of Chemistry, College of Science, United Arab Emirates University</institution>, <addr-line>Al Ain</addr-line>, <country>United Arab Emirates</country></aff>
<aff id="aff15"><sup>15</sup><institution>Faculty of Medicine, University of Debrecen</institution>, <addr-line>Debrecen</addr-line>, <country>Hungary</country></aff>
<aff id="aff16"><sup>16</sup><institution>Harry Butler Institute, Murdoch University</institution>, <addr-line>Perth, WA</addr-line>, <country>Australia</country></aff>
<aff id="aff17"><sup>17</sup><institution>Food Microbiology and Biotechnology Laboratory, Food and Nutritional Science Program, North Carolina A&amp;T State University</institution>, <addr-line>Greensboro, NC</addr-line>, <country>United States</country></aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Wuquan Deng, Chongqing Emergency Medical Center, China</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Marcella Reale, University of Studies G. d&#x2019;Annunzio Chieti and Pescara, Italy</p>
<p>Shahzad Munir, Yunnan Agricultural University, China</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Synan F. AbuQamar, <email xlink:href="mailto:sabuqamar@uaeu.ac.ae">sabuqamar@uaeu.ac.ae</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>10</day>
<month>06</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1277074</elocation-id>
<history>
<date date-type="received">
<day>13</day>
<month>08</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>06</day>
<month>05</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 El-Saadony, Saad, Korma, Salem, Abd El-Mageed, Alkafaas, Elsalahaty, Elkafas, Mosa, Ahmed, Mathew, Albastaki, Alkuwaiti, El-Tarabily, AbuQamar, El-Tarabily and Ibrahim</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>El-Saadony, Saad, Korma, Salem, Abd El-Mageed, Alkafaas, Elsalahaty, Elkafas, Mosa, Ahmed, Mathew, Albastaki, Alkuwaiti, El-Tarabily, AbuQamar, El-Tarabily and Ibrahim</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>Garlic (<italic>Allium sativum</italic> L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many <italic>in vitro</italic> and <italic>in vivo</italic> studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, &#x3b2;-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and &#x3b2;-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.</p>
</abstract>
<kwd-group>
<kwd><italic>Allium sativum</italic>
</kwd>
<kwd>bioactive compounds</kwd>
<kwd>functional foods</kwd>
<kwd>human diseases</kwd>
<kwd>human health</kwd>
<kwd>mechanisms of action</kwd>
<kwd>toxicity</kwd>
</kwd-group>
<counts>
<fig-count count="5"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="235"/>
<page-count count="25"/>
<word-count count="11457"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Nutritional Immunology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Garlic (<italic>Allium sativum</italic> L.) is a member of the Liliaceae family (<xref ref-type="bibr" rid="B1">1</xref>). The genus <italic>Allium</italic> contain hundreds of species, including garlic, onion, shallot, leek and chive, that are known for their physiologically active secondary metabolites (<xref ref-type="bibr" rid="B2">2</xref>). Garlic is an ancient crop that is native to Central and South Asia, and northeastern Iran (<xref ref-type="bibr" rid="B3">3</xref>). Garlic has compact bulbs, and each bulb consists of several bulblets/cloves that are covered with a white skin (<xref ref-type="bibr" rid="B4">4</xref>). Its products, including garlic oil macerates, essential oils (EOs), garlic powder, and aged garlic extract (<xref ref-type="bibr" rid="B5">5</xref>) exhibit a noteworthy therapeutic impact (<xref ref-type="bibr" rid="B6">6</xref>). Thus, they are economically important due to their nutraceutical characteristics and health advantages (<xref ref-type="bibr" rid="B7">7</xref>).</p>
<p>The raw garlic-derived compounds contain organosulfur components susceptible to oxidation, volatilization, and deterioration when exposed to unfavorable conditions such as light, oxygen, and high temperatures (<xref ref-type="bibr" rid="B8">8</xref>). These components are also thermodynamically unstable. Encapsulation methods utilizing a range of wall materials and technologies were implemented to enhance the stability and suitability of the bioactive constituents in garlic for use in the food industry. The principal organosulfur components found in garlic essential oil are as follows: diallyl sulfide (DAS), dimethyl trisulfide, diallyl tetrasulfide, methyl disulfide, allyl methyl trisulfide, diallyl trisulfide, allyl disulfide, and allyl methyl tetrasulfide (<xref ref-type="bibr" rid="B9">9</xref>). Aqueous and alcoholic garlic extract (GE) contain S-allyl-mercapto cysteine (SAMC), S-methyl-l-cysteine, S-propenyl-l-cysteine, and S-allyl-cysteine, all of which are derived from &#x3b3;-glutamyl-S-allyl-L-cysteines (<xref ref-type="bibr" rid="B10">10</xref>).</p>
<p>This comprehensive review provides recent experimental and clinical reports. It will encompass an analysis of the safety profile, metabolism pathway, bioavailability, biological and therapeutic effects, food-related applicability, adulteration detection methods, potential toxicities, and bioactive compounds derived from garlic. We believe that by publishing this review paper, more people will be interested in garlic and that it will provide up-to-date scientific data for enhanced garlic use in human health as well as illness management.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Methodology</title>
<sec id="s2_1">
<label>2.1</label>
<title>Study design</title>
<p>The study reviews relevant and current literature on bioavailability, biological and therapeutic effects, food-related applicability, adulteration detection methods, potential toxicities, and bioactive compounds derived from garlic.</p>
</sec>
<sec id="s2_2">
<label>2.2</label>
<title>Data collection</title>
<p>Data were collected from related past and recent textbooks, proceedings, and research articles using PubMed, Scopus, Google Scholar, and Web of Science. The keywords were <italic>Allium sativum</italic>, bioactive compounds, functional foods, human health, human diseases, mechanisms of action, and toxicity.</p>
<p>All kinds of related articles and abstracts were included. Criteria were set to studies published in the last five years as much as possible. Following the outlined searches, articles were chosen based on their relevance to the objective of this review. Articles providing information in clear relation to garlic active compounds and their pharmacological effects, with a clear indication of their action mechanisms, were also included. A total of 235 articles were included in this review.</p>
</sec>
</sec>
<sec id="s3">
<label>3</label>
<title>Botanical description</title>
<p>Garlic is an herbaceous plant with a fragrant stem segregated into 6 to 12 bulblets named garlic cloves, linked by a fine shell to create the garlic head (<xref ref-type="bibr" rid="B11">11</xref>). The roots of garlic emerge from the disc&#x2019;s basal part and can grow to a depth of at least 80 cm closer to the plant&#x2019;s base. Its leaves are morphologically long, narrow, and flat; however, the tip is cylindrical and sharp (<xref ref-type="bibr" rid="B12">12</xref>). The flowers are tiny and whitish purple.</p>
<p>Garlic cultivation necessitates thick clay soil, humus, and enough water (<xref ref-type="bibr" rid="B13">13</xref>). A 70&#x2013;80 cm height characterizes the garlic plant; several leaves are 13&#x2013;15, the weight of the bulb is 50 g with a diameter of 5 cm, the number of teeth is 12&#x2013;13, the period of growth in sowing winter is 250 days, and 40-day delay (<xref ref-type="bibr" rid="B14">14</xref>). <xref ref-type="table" rid="T1"><bold>Table&#xa0;1</bold></xref> summarizes the different parts of garlic, its active compounds, and their effects.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>The active compounds and their biological activities associated with different garlic parts.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Active part</th>
<th valign="middle" align="left">Active compounds</th>
<th valign="middle" colspan="2" align="left">Molecular Formula and weight</th>
<th valign="top" align="center">Activity</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<th valign="top" colspan="6" align="left">Sulfur compounds</th>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Methiin</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>9</sub>NO<sub>3</sub>S</td>
<td valign="top" align="left">151.19</td>
<td valign="top" align="left">Anticancer; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B15">15</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Ethiin</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>11</sub>NO<sub>3</sub>S</td>
<td valign="top" align="left">165.21</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B15">15</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Isoalliin</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>11</sub>NO<sub>3</sub>S</td>
<td valign="top" align="left">177.22</td>
<td valign="top" align="left">Anticancer; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B15">15</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Leaf</td>
<td valign="top" align="left">Alliin</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>11</sub>NO<sub>3</sub>S</td>
<td valign="top" align="left">177.22</td>
<td valign="top" align="left">Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B16">16</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Propenesulfenic acid</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>OS</td>
<td valign="top" align="left">90.14</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B17">17</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Diallyl sulfide</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>S</td>
<td valign="top" align="left">114.21</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Dimethyl disulfide</td>
<td valign="top" align="left">C<sub>2</sub>H<sub>6</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">94.20</td>
<td valign="top" align="left">Antithrombotic</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Propenesulfinic acid</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>O<sub>2</sub>S</td>
<td valign="top" align="left">106.14</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B17">17</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Methyl-(E-<italic>Z</italic>)-1-propenyl disulfide</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">120.24</td>
<td valign="top" align="left">Antithrombotic; Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">(<italic>E-Z</italic>)-1-Propenyl-2-propenyl disulfide</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">146.30</td>
<td valign="top" align="left">Antithrombotic; Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">(E-<italic>Z</italic>)-Methyl-1-propenyl disulfide-5-Oxide</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>OS<sub>2</sub>
</td>
<td valign="top" align="left">136.24</td>
<td valign="top" align="left">Antithrombotic; Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B17">17</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Propeneperthiol</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">106.21</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">20</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Allyl methyl disulfide</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">120.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Allyl methyl thiosulfinates</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>OS<sub>2</sub>
</td>
<td valign="top" align="left">136.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">20</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Isoallyl methyl thiosulfinates</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>OS<sub>2</sub>
</td>
<td valign="top" align="left">136.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">20</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left"><italic>S</italic>-Allylmercapto-L-cysteine</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>11</sub>NO<sub>2</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">193.30</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B21">21</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left"><italic>&#x3b3;</italic>-L-Glutamyl-<italic>S</italic>-allylthio-L-cysteine</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>18</sub>N<sub>2</sub>O<sub>5</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">322.40</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B22">22</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Allithiamine</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>22</sub>N<sub>4</sub>O<sub>2</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">354.50</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B23">23</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Methyl methanethiosulfinate</td>
<td valign="top" align="left">C<sub>2</sub>H<sub>6</sub>OS<sub>2</sub>
</td>
<td valign="top" align="left">110.20</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B20">20</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Dihydroasparagusic acid</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>O<sub>2</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">152.20</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B24">24</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Dimethyl trisulfide</td>
<td valign="top" align="left">C<sub>2</sub>H<sub>6</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">126.30</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Allyl-1-propenyl trisulfide</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">178.30</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">25</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Methyl-2-propenyl trisulfide</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>8</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">152.30</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">26</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Diallyl trisulfide</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>10</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">178.30</td>
<td valign="top" align="left">Antithrombotic; Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">25</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Ajoene</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>14</sub>OS<sub>3</sub>
</td>
<td valign="top" align="left">234.40</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">27</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Allyl propyl trisulfide</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>12</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">180.40</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Ajocysteine</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>15</sub>NO<sub>3</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">281.40</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">27</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">1,2-Dithiolene</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>4</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">104.20</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Leaf</td>
<td valign="top" align="left">Foliogarlic trisulfane</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>16</sub>O<sub>6</sub>S<sub>3</sub>
</td>
<td valign="top" align="left">352.45</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Leaf</td>
<td valign="top" align="left">Foliogarlic disulfanes</td>
<td valign="top" align="left">C<sub>12</sub>H<sub>16</sub>O<sub>6</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">320.38</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Garlicnin</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>16</sub>O<sub>2</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">220.35</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B29">29</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">1,2-Dithiolane</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>S<sub>2</sub>
</td>
<td valign="top" align="left">106.21</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">Amino acids and their derivatives</th>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Valine</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>11</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">117.15</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">&#x3b1;-Aminobutyric acid</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>9</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">103.12</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B31">31</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Choline</td>
<td valign="top" align="left">C5H<sub>14</sub>NO<sup>+</sup>
</td>
<td valign="top" align="left">104.17</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Proline</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>9</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">115.13</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">5-Oxoproline</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>7</sub>NO<sub>3</sub>
</td>
<td valign="top" align="left">129.11</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Aspartic acid</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>7</sub>NO<sub>4</sub>
</td>
<td valign="top" align="left">133.10</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Glutamic acid</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>9</sub>NO<sub>4</sub>
</td>
<td valign="top" align="left">147.13</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Lysine</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">146.19</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Hydroxylysine</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>3</sub>
</td>
<td valign="top" align="left">162.19</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Arginine</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>14</sub>N<sub>4</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">174.20</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Leucine</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>13</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">131.17</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Se-Methylselenocysteine</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>9</sub>NO<sub>2</sub>Se</td>
<td valign="top" align="left">182.09</td>
<td valign="top" align="left">Cardioprotective</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">&#x3b3;-Glutamyl-Se-methylselenocysteine</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>15</sub>N<sub>2</sub>O<sub>5</sub>Se<sub>-</sub>
</td>
<td valign="top" align="left">310.20</td>
<td valign="top" align="left">Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">Oxygenic compounds</th>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Myristic acid</td>
<td valign="top" align="left">C<sub>14</sub>H<sub>28</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">228.37</td>
<td valign="top" align="left">Cardioprotective; Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Palmitic acid</td>
<td valign="top" align="left">C<sub>16</sub>H<sub>32</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">256.42</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Oleic acid</td>
<td valign="top" align="left">C<sub>18</sub>H<sub>34</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">282.50</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Aminoacrylic acid</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>5</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">87.08</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Lactic acid</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>O<sub>3</sub>
</td>
<td valign="top" align="left">90.08</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Succinic acid</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>6</sub>O<sub>4</sub>
</td>
<td valign="top" align="left">118.09</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Malic acid</td>
<td valign="top" align="left">C<sub>4</sub>H<sub>6</sub>O<sub>5</sub>
</td>
<td valign="top" align="left">134.09</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Arabinoic acids</td>
<td valign="top" align="left">C<sub>5</sub>H<sub>10</sub>O<sub>6</sub>
</td>
<td valign="top" align="left">166.13</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Mandelic acid</td>
<td valign="top" align="left">C<sub>8</sub>H<sub>8</sub>O<sub>3</sub>
</td>
<td valign="top" align="left">152.15</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Carvacrol</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>14</sub>O</td>
<td valign="top" align="left">150.22</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Carvone</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>14</sub>O</td>
<td valign="top" align="left">150.22</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left"><italic>p</italic>-Tert-butylphenol</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>14</sub>O</td>
<td valign="top" align="left">150.22</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Linalool</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>18</sub>O</td>
<td valign="top" align="left">154.25</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">4-(1,1-Dimethylpropyl) phenol</td>
<td valign="top" align="left">C<sub>11</sub>H<sub>16</sub>O</td>
<td valign="top" align="left">164.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Methylene-4-pentenal</td>
<td valign="top" align="left">C<sub>6</sub>H<sub>8</sub>O</td>
<td valign="top" align="left">96.13</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Ammonium pyruvate</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>7</sub>NO<sub>3</sub>
</td>
<td valign="top" align="left">105.09</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">33</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Geraniol</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>18</sub>O</td>
<td valign="top" align="left">154.25</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">26</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Propen-1-ol</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>6</sub>O</td>
<td valign="top" align="left">58.08</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">2-Hydroxy propanamide</td>
<td valign="top" align="left">C<sub>3</sub>H<sub>7</sub>NO<sub>2</sub>
</td>
<td valign="top" align="left">89.09</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Retinoyl-&#x3b2;-glucuronic acid</td>
<td valign="top" align="left">C<sub>26</sub>H<sub>36</sub>O<sub>8</sub>
</td>
<td valign="top" align="left">476.60</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">Phenolic compounds</th>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Eugenol-1-O-rutinoside</td>
<td valign="top" align="left">C<sub>22</sub>H<sub>32</sub>O<sub>11</sub>
</td>
<td valign="top" align="left">472.48</td>
<td valign="top" align="left">Cardioprotective</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Root</td>
<td valign="top" align="left"><italic>N</italic>-Feruloyltyramine</td>
<td valign="top" align="left">C<sub>18</sub>H<sub>19</sub>NO<sub>4</sub>
</td>
<td valign="top" align="left">313.30</td>
<td valign="top" align="left">Immunomodulatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Root</td>
<td valign="top" align="left"><italic>N</italic>-Feruloyltyrosine</td>
<td valign="top" align="left">C<sub>19</sub>H<sub>19</sub>NO<sub>6</sub>
</td>
<td valign="top" align="left">357.40</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Husk waste</td>
<td valign="top" align="left"><italic>p</italic>-Coumaric acid</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>8</sub>O<sub>3</sub>
</td>
<td valign="top" align="left">164.16</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Husk waste</td>
<td valign="top" align="left">Ferulic acid</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>10</sub>O<sub>4</sub>
</td>
<td valign="top" align="left">194.18</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Husk waste</td>
<td valign="top" align="left">Caffeic acid</td>
<td valign="top" align="left">C<sub>9</sub>H<sub>8</sub>O<sub>4</sub>
</td>
<td valign="top" align="left">180.16</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Apigenin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>10</sub>O<sub>5</sub>
</td>
<td valign="top" align="left">270.24</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">26</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Quercetin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>10</sub>O<sub>7</sub>
</td>
<td valign="top" align="left">302.23</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">26</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Myricetin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>10</sub>O<sub>8</sub>
</td>
<td valign="top" align="left">318.23</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Naringenin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>12</sub>O<sub>5</sub>
</td>
<td valign="top" align="left">272.25</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Catechin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>14</sub>O<sub>6</sub>
</td>
<td valign="top" align="left">290.27</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Gallocatechol</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>14</sub>O<sub>7</sub>
</td>
<td valign="top" align="left">306.27</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Tangeretin</td>
<td valign="top" align="left">C<sub>20</sub>H<sub>20</sub>O<sub>7</sub>
</td>
<td valign="top" align="left">372.40</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Nobiletin</td>
<td valign="top" align="left">C<sub>21</sub>H<sub>22</sub>O<sub>8</sub>
</td>
<td valign="top" align="left">402.40</td>
<td valign="top" align="left">Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Rutin</td>
<td valign="top" align="left">C<sub>27</sub>H<sub>30</sub>O<sub>16</sub>
</td>
<td valign="top" align="left">610.50</td>
<td valign="top" align="left">Anticancer; Anti-inflammatory; Antimicrobial; Antioxidant</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">26</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Theophylline</td>
<td valign="top" align="left">C<sub>7</sub>H<sub>8</sub>N<sub>4</sub>O<sub>2</sub>
</td>
<td valign="top" align="left">180.16</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Nicotine</td>
<td valign="top" align="left">C<sub>10</sub>H<sub>14</sub>N<sub>2</sub>
</td>
<td valign="top" align="left">162.23</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Cyanidin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>11</sub>O<sub>6</sub>
</td>
<td valign="top" align="left">287.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Delphinidin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>11</sub>ClO<sub>7</sub>
</td>
<td valign="top" align="left">338.69</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Anthocyanin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>11</sub>O</td>
<td valign="top" align="left">207.25</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Bulb</td>
<td valign="top" align="left">Pelargonidin</td>
<td valign="top" align="left">C<sub>15</sub>H<sub>11</sub>O</td>
<td valign="top" align="left">271.24</td>
<td valign="top" align="left">Antimicrobial; Antioxidant; Anticancer; Anti-inflammatory</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">30</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s4">
<label>4</label>
<title>Phytochemical compounds in garlic</title>
<p>Approximately 184 diverse types of active secondary metabolites are found in garlic (<xref ref-type="bibr" rid="B38">38</xref>). Almost 90% of these metabolites are characterized as the following: 70 organosulfur, 29 saponins, 16 flavonoids, 12 amino acids, and phenyl prostanoids 10 for each of phenyl prostanoids, 7 alkaloids, in addition to 3 compounds of fatty acids, and selenium derivatives (<xref ref-type="bibr" rid="B38">38</xref>). In leaves, the active secondary metabolites represent nine compounds, while in roots and husk wastes, there are 6 and 3 compounds, respectively. In general, there are 166 plant chemicals in bulbs and cloves (<xref ref-type="bibr" rid="B39">39</xref>).</p>
<sec id="s4_1">
<label>4.1</label>
<title>Bioactive compounds of garlic</title>
<p>Due to its many phytochemicals, minerals, and dietary fiber, garlic is considered a valuable spice. Moderate amounts of selenium, calcium, magnesium, manganese, iron, vitamins A, C, and B complex, and sodium are also present. Potassium, zinc, sulfur, and phosphorus are all found in substantial concentrations (<xref ref-type="bibr" rid="B40">40</xref>). Dietary fiber comprises approximately 1.5% of the garlic bulb&#x2019;s composition, followed by protein (2%), organosulfur substances (2.3%), carbohydrates (28%), and water (65%) (<xref ref-type="bibr" rid="B41">41</xref>).</p>
<p>The principal bioactive components of these substances have recently sparked widespread scientific attention. These include a variety of substances such as phenols, enzymes (myrosinase, allinase, peroxidase), polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, &#x3b2;-phellandrene, ajoene, alliin, SAMC, and &#x3b2;-phellandrene. A limited selection of the recognized polyphenolic constituents found in the matrix of garlic include apigenine, kaempferol-3-O-glucoside-7-O-alpha-l-rhamnoside, kaempferol 3,7-di-O-rhamnoside, luteoline, and kaempferol-3-O-glucoside (<xref ref-type="bibr" rid="B42">42</xref>). Furthermore, it comprises 17 amino acids, of which 8 are primary (<xref ref-type="bibr" rid="B43">43</xref>). Although intact garlic typically comprises advantageous constituents, further analysis has revealed the presence of additional substances, including DAS, dithiine, diallyl disulfide (DADS), allicin, and ajoene, which are the result of diverse chemical reactions occurring during pulverizing or chopping (<xref ref-type="bibr" rid="B44">44</xref>). <xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1</bold></xref> depicts the major water-soluble and oil-soluble sulfur compounds present in garlic.</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Major water and oil-soluble sulfur compounds found in garlic.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1277074-g001.tif"/>
</fig>
<p>The primary chemical composition and profiles of bioactive components in garlic are significantly influenced by various factors, such as genotype, irrigation, temperature, light, and fertilization during the pre-harvest period; harvest and post-harvest conditions, ventilation, relative humidity, and temperature (<xref ref-type="bibr" rid="B45">45</xref>). As illustrated in <xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1</bold></xref>, dehydrated or whole garlic contains organosulfur components such as &#x3b3;-glutamylcysteine and alliin (S-allylcysteine sulfoxide). These components are biogenic facilitators for generating additional sulfur byproducts throughout garlic production and heating (<xref ref-type="bibr" rid="B46">46</xref>). Alliinase enzymes (EC 4.4.1.14), which are initially limited to the cells of the vascular bundle sheath and rapidly convert alliin (which is categorized in mesophyll cells) to allicin, are released during cutting, crushing, or timidity (<xref ref-type="bibr" rid="B47">47</xref>).</p>
</sec>
<sec id="s4_2">
<label>4.2</label>
<title>Allicin contents</title>
<p>Allicin, the principal S-molecule in garlic, comprises approximately 70&#x2013;80% of its bioactive compounds and is accountable for imparting its distinctive aroma (<xref ref-type="bibr" rid="B48">48</xref>). Allicin rapidly decomposes and generates other stable organosulfur constituents, including DADS, diallyl trisulfides, vinyldithiines (3-vinyl-4H-1,2-dithiin and 2-vinyl-4H-1,3-dithiin), DAS, and ajoenes (<xref ref-type="bibr" rid="B49">49</xref>). These constituents are sensitive to organic solvents, oxygen, temperature, and pH. The various physiological and biological attributes of garlic, including its antidiabetic, anti-cancer, anti-inflammatory, antiobesity, antioxidant, antifungal, antibacterial, and immunomodulatory properties, can be primarily attributed to the bioactive constituents present in its matrix. These include organosulfur compounds (e.g., allicin, DAS, allyl propyl disulfide, diallyl polysulfides, vinyldithiins, DADS, and diallyl trisulfide) (<xref ref-type="bibr" rid="B49">49</xref>).</p>
</sec>
<sec id="s4_3">
<label>4.3</label>
<title>E- and z-ajoene content</title>
<p>Ajoene is a group of organosulfur compounds with garlic-like characteristics (<xref ref-type="bibr" rid="B45">45</xref>). The biological activities of garlic are linked to various compounds, including ajoene, produced through allicin breakdown and non-enzymatic repair (<xref ref-type="bibr" rid="B50">50</xref>). In cancer cells, it has been shown triggering apoptosis (<xref ref-type="bibr" rid="B51">51</xref>); thus having an anti-cancer impact. Ajoene has been demonstrated to decrease the proliferation of lung cancer cells in some studies (<xref ref-type="bibr" rid="B52">52</xref>). Ajoene is also an antifungal medication that is safe and successful in treating chromoblastomycosis and dermatophytosis (<xref ref-type="bibr" rid="B53">53</xref>). Its inhibitory dose can be below 20 &#xb5;g/ml (<xref ref-type="bibr" rid="B54">54</xref>, <xref ref-type="bibr" rid="B55">55</xref>). Choi et&#xa0;al. (<xref ref-type="bibr" rid="B56">56</xref>) employed ajoene at 3 &#xb5;g/ml extract concentrations to boost macrophage antimycobacterial activity. Ajoene can also disrupt biological machinery and is lethal to cancer cells at low &#xb5;M concentrations (<xref ref-type="bibr" rid="B57">57</xref>).</p>
</sec>
</sec>
<sec id="s5">
<label>5</label>
<title>Bioavailability of active compounds after metabolism</title>
<p>Allicin and other biological sulfur compounds found in garlic are believed to be the primary pharmacologically active components of the matrix due to their potent anticancer, antibacterial, and antioxidant properties. Absorption in the intestines is a critical factor in the health-promoting effects of the biological components in garlic. The absorption rate significantly influences the availability of these compounds (<xref ref-type="bibr" rid="B58">58</xref>).</p>
<p>Investigating how compounds are absorbed into the body, particularly in relation to food, is a fascinating trend in research across different fields (<xref ref-type="bibr" rid="B58">58</xref>). Based on <italic>in vitro</italic> experiments concerning the potential of raw garlic and its preparation in cancer treatment, <italic>in vivo</italic> studies and clinical trials have been initiated, albeit their contradictory results (<xref ref-type="bibr" rid="B59">59</xref>). Indeed, variations exist regarding the bioavailability of the sulfur-containing primary groups when comparing fresh garlic to specific culinary and medicinal preparations that incorporate garlic. <italic>In vivo</italic> research investigated the bioavailability of allicin from 13 garlic supplements and 9 meals in 13 participants by quantifying allyl methyl sulfide, the principal garlic metabolite, in their breath. The bioavailability of allicin supplements was found to be higher than freshly pulverized garlic (<xref ref-type="bibr" rid="B59">59</xref>).</p>
<p>Allicin is responsible for the majority of the pharmacological effects of raw garlic. When inhibiting enzymes in the gastrointestinal tract, it is swiftly biotransformed (half-life &lt;1 min) to allyl mercaptan. Upon consuming a substantial quantity (25 g) of crushed fresh garlic, allicin and its metabolites have been detected in the urine, feces, and blood (<xref ref-type="bibr" rid="B60">60</xref>). Allicin is metabolized into secondary compounds, including E-ajoene, 2-ethenyl-4H-1, 3-dithiin, and DADS, much like how rapidly it exited the body following intravenous infusion (<xref ref-type="bibr" rid="B61">61</xref>).</p>
<p>Furthermore, approximately 30 min after ingestion, the bioavailability of allicin from enteric-coated tablet formulations varied between 36 and 104%. However, when inhaled with a protein-rich meal, the bioavailability decreased from 22 to 57% (<xref ref-type="bibr" rid="B59">59</xref>). The bioavailability of garlic capsules was 26&#x2013;109% lower than that of non-enteric-coated tablets (<xref ref-type="bibr" rid="B59">59</xref>). Furthermore, the cysteine protein derivative interacts quantitatively with allicin at the temperature of the host gut to generate two equivalents of SAMC. This occurs when cysteine produced from ingested food protein interacts with allicin in garlic supplements in the gastrointestinal environment (<xref ref-type="bibr" rid="B59">59</xref>).</p>
<p>In an <italic>in vivo</italic> experiment using mice, the principal metabolites allyl methyl sulfone and allyl methyl sulfoxide were detected in the liver, stomach, plasma, and urine after DADS (200 mg/kg) was administered orally (<xref ref-type="bibr" rid="B62">62</xref>). Metabolic analysis of DADS radioactively tagged in mouse livers revealed that 70% of the radioactive substance was present in the cytoplasm; however, it did not exist in the form of DADS. DADS constituted 80% of the radioactivity (<xref ref-type="bibr" rid="B63">63</xref>). This research indicates that sulfur compounds derived from the metabolism of allicin are primarily responsible for physiological effects. One of the chemical compounds generated by these substances is hydrogen sulfide, which functions as a signal transduction substance within the human body (<xref ref-type="bibr" rid="B64">64</xref>).</p>
<p>Aged garlic extract is composed primarily of water-soluble organosulfur compounds, including S-allyl cysteine (SAC) and SAMC, which have a distinct pharmacokinetic profile compared to oil-soluble organosulfur elements (<xref ref-type="bibr" rid="B65">65</xref>). In addition, garlic is rapidly absorbed from the gastrointestinal tract, and SAC has a half-life of over 10 h and a renal clearance of over 30 h in humans. Based on SAC&#x2019;s efficacy and safety assessment, it appears to significantly impact the biological characteristics (<xref ref-type="bibr" rid="B66">66</xref>). Effective <italic>in vitro</italic> extraction methods can reduce potential toxicity while enhancing the bioavailability of garlic. During the extraction of aged garlic extract, the garlic matrix&#x2019;s undesirable constituents are transformed into S-components securely and consistently. Several toxicological investigations have also confirmed the safety of aged garlic extract (<xref ref-type="bibr" rid="B67">67</xref>).</p>
<p>It is noteworthy that although organic S-compounds (OSCs) have a low bioavailability in the host body, research indicates that incorporating garlic into one&#x2019;s daily diet can provide sufficient quantities to support their biological effects. Aryl and methyl are the two most prevalent forms of OSCs identified in garlic extract (<xref ref-type="bibr" rid="B68">68</xref>). SAC was found to have a relatively high bioavailability in the blood plasma, kidneys, and liver of primary animal experiments involving canine and mouse models exposed to aqueous garlic extracts (<xref ref-type="bibr" rid="B69">69</xref>). Garlic yielded 570 &#x3bc;g of DADS, 2.5 mg of allicin, and 60 &#x3bc;g of SAC, all of which are equivalent to 1000 &#x3bc;g of diallyl trisulfides (<xref ref-type="bibr" rid="B69">69</xref>).</p>
<p>After ingestion, the purified allicin was not detected in the blood, urine, or feces (<xref ref-type="bibr" rid="B70">70</xref>). An element that contributes to the diminished biological accessibility of allicin is its tendency to form bonds with fatty acids and proteins across plasma membranes (<xref ref-type="bibr" rid="B71">71</xref>). Some hypotheses regarding these barriers encompassed the challenge of allicin evading the digestive tract via its interaction with the intestinal mucosa and its oxidative reaction with red blood cells (<xref ref-type="bibr" rid="B71">71</xref>). Furthermore, it was characterized by its high reactivity and rapid conversion to allyl mercaptan (AM) (<xref ref-type="bibr" rid="B71">71</xref>).</p>
<p>A simulated digestion method was employed to investigate the impact of temperature, duration, pH, and neutralization after acidification on thiosulfate (TS) synthesis from garlic powder and cloves (<xref ref-type="bibr" rid="B60">60</xref>). An optimal pH range of 4.5-5.0 was identified as the setting for synthesizing allicin, allyl 1-propenyl, and 1-propenyl allyl (<xref ref-type="bibr" rid="B72">72</xref>). The best formations of allyl methyl+methylallyl and 1-propenyl methyl+methyl 1-propenyl occurred between pH 6.5-7.0. Dimethyl generated thiosulfinate at pH 5.5 and no TS below pH 3.6 (<xref ref-type="bibr" rid="B72">72</xref>). However, the pH of the intestines and stomach did not significantly influence the bioavailability or gastrointestinal metabolism of allicin. Although overall temperature had a negligible impact on the production of TS, the allicin experienced the most excellent disintegration and degradation at 35&#xb0;C (<xref ref-type="bibr" rid="B72">72</xref>). Hydrolyzing allicin and alliin produced water-soluble compounds with enhanced antioxidant, bioavailability, and stability properties (<xref ref-type="bibr" rid="B72">72</xref>).</p>
<p>It is noteworthy to mention that the abrasive sensation experienced during garlic consumption can be attributed to the vasodilatory effects of DADS and allicin, which are produced by allyl isothiocyanate neurons stimulated by capsaicin neural terminals (<xref ref-type="bibr" rid="B70">70</xref>). In addition, increasing the levels of bioavailable substances, including DAS, ajoene, diallyl trisulfide, DADS, and SAC, and altering the expression of the DMT1 mRNA gene, garlic consumption can enhance iron absorption from carbonyl iron (<xref ref-type="bibr" rid="B73">73</xref>). Shallots and leeks have also been proposed to increase iron bioavailability in cereals and legumes (<xref ref-type="bibr" rid="B74">74</xref>).</p>
<p>Evaluations of sulfur constituents in different garlic substrates via <italic>in vitro</italic> digestion revealed that garlic powder exhibited the most significant accessibility, followed by garlic cloves. Nevertheless, there was a reduction in allicin availability when it was ingested alongside high-protein meals due to the subsequent delayed gastric emptying (<xref ref-type="bibr" rid="B75">75</xref>). Diverse organic sulfides may be produced from garlic through its multifaceted processing. The organic sulfides in question demonstrate an extensive array of significant biological and therapeutic attributes (<xref ref-type="bibr" rid="B75">75</xref>). Additional research into the bioavailability of various organic sulfides is crucial for expanding the pharmaceutical and health product industries involving garlic.</p>
</sec>
<sec id="s6">
<label>6</label>
<title>Biological activities and nutraceutical properties of garlic</title>
<p>The ancient Egyptians well-documented the antiquity of garlic as a remedy for respiratory and gastrointestinal ailments. They also incorporated it into a diverse array of nutritional and therapeutic products (<xref ref-type="bibr" rid="B76">76</xref>). Louis Pasteur was the initial proponent of the antibacterial properties of garlic in 1858. The enzymatic activity of alliin alkyl-sulfonate-lyase transforms the inactive constituent of garlic, alliin (a sulfoxide derivative of the cysteine amino acid), into allicin (diallyl thiosulfinate), which is the bioactive element accountable for the antibacterial properties of garlic (<xref ref-type="bibr" rid="B76">76</xref>). <xref ref-type="table" rid="T2"><bold>Table&#xa0;2</bold></xref> and <xref ref-type="fig" rid="f2"><bold>Figure&#xa0;2</bold></xref> summarize the different biological activities of garlic and garlic products.</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Biological activities of garlic and garlic-derived compounds.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">Extract/Product</th>
<th valign="middle" align="left">Active compound</th>
<th valign="middle" align="left">Activity</th>
<th valign="middle" align="left">Host</th>
<th valign="middle" align="left">Mechanism</th>
<th valign="middle" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" rowspan="22" align="left"><bold>Aged garlic extract</bold>
</td>
<td valign="middle" align="left">Eruboside B</td>
<td valign="middle" align="left"><italic>In vivo</italic> antioxidant</td>
<td valign="middle" align="left">Mouse myoblasts challenged by C2Cl2</td>
<td valign="middle" align="left">Mitigating oxidative stress</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B77">77</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Iso- Eruboside B</td>
<td valign="middle" align="left"><italic>In vitro</italic> antioxidant</td>
<td valign="middle" align="left">Human endothelial cells</td>
<td valign="middle" align="left">Scavenging H<sub>2</sub>O<sub>2</sub>, maintaining cell growth and protecting DNA from damage</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B78">78</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">SW480, SW620, A598, ECV304 cancer cells lines</td>
<td valign="middle" align="left">Reducing invasive activity, reducing invasive activity, preventing cell division, and inhibiting endothelial cell tube formation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B79">79</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">DLD-1 colon cancer cells</td>
<td valign="middle" align="left">Inhibiting cell viability through<break/>inhibiting NF-&#x3ba;B activity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B80">80</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic> anticancer</td>
<td valign="middle" align="left">Adult albino rat challenged by cisplatin</td>
<td valign="middle" align="left">Enhancing renal histological, ultrastructural, and biochemical alterations, including hemorrhage, glomerular atrophy, tubular necrosis, and degeneration</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B81">81</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic> anticancer</td>
<td valign="middle" align="left">BALB/c mice injected with fibrosarcoma tumors</td>
<td valign="middle" align="left">Enhancing the mice&#x2019;s immunity to fibrosarcoma and inhibit tumor development.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B82">82</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Ethyl linoleate</td>
<td valign="middle" align="left"><italic>In vitro</italic>
<break/>anti-inflammatory</td>
<td valign="middle" align="left">RAW 264.7 macrophages induced by lipopolysaccharide</td>
<td valign="middle" align="left">Limiting prostaglandin E-2 and NO release</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B83">83</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left">Allicin</td>
<td valign="middle" rowspan="2" align="left"><italic>In vivo</italic>
<break/>anti-inflammatory</td>
<td valign="middle" align="left">BALB/c mice</td>
<td valign="middle" align="left">Preventing the inflammatory reaction</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B84">84</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">40 Obese patients</td>
<td valign="middle" align="left">Providing osteoarthritis relief</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B85">85</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">14-KDa protein</td>
<td valign="middle" align="left"><italic>In vitro</italic>
<break/>anti-inflammatory</td>
<td valign="middle" align="left">J774A1 macrophages induced by lipopolysaccharide</td>
<td valign="middle" align="left">Impairing proinflammatory cytokines, including NO, TNF-&#x3b1;, and IL-1&#x3b2;</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B86">86</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Fru-Arg</td>
<td valign="middle" align="left"><italic>In vitro</italic>
<break/>neuroprotection</td>
<td valign="middle" align="left">Microglial cells from murine BV-2 induced by lipopolysaccharide</td>
<td valign="middle" align="left">Regulating protein expression in mitigating the oxidative stress causes, reducing nerve inflammation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B87">87</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>neuroprotection</td>
<td valign="middle" rowspan="2" align="left">Wister rats</td>
<td valign="middle" align="left">Reducing the degradation of working memory</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B88">88</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>protection of the digestive system</td>
<td valign="middle" align="left">Preventing the ulceration caused by indomethacin</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B89">89</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>protection of the digestive system</td>
<td valign="middle" align="left">Albino rats</td>
<td valign="middle" align="left">Restoring the damaged stomach mucosa caused by indomethacin, reducing the overall number of microbes in the stomach</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B90">90</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Allicin</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>protection of the digestive system</td>
<td valign="middle" align="left">Induced colitis mice</td>
<td valign="middle" align="left">Dextran sulfate sodium inducing ulcerative colitis, which can be alleviated by garlic extract</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B91">91</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study<break/>cardiovascular</td>
<td valign="middle" align="left">41 patients with<break/>hypercholesterolemia</td>
<td valign="middle" align="left">Reducing the activity of lipid hydroperoxide and serum myeloperoxidase, reducing F2-isoprostane concentrations in plasma and urine</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B92">92</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study<break/>immunity</td>
<td valign="middle" align="left">56 healthy human participants</td>
<td valign="middle" align="left">Reducing the incidence of cold and influenza Enhancing the immune system&#x2019;s performance</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B93">93</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Allicin</td>
<td valign="middle" align="left"><italic>In vitro</italic> antimicrobial</td>
<td valign="middle" align="left"><italic>Aspergillus versicolor</italic> and <italic>Penicillium expansum</italic>
</td>
<td valign="middle" align="left">Inhibiting microbial population</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B94">94</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vitro</italic> antimicrobial</td>
<td valign="middle" align="left"><italic>Penicillum citrinum, Burkholderia cepacian</italic>
</td>
<td valign="middle" align="left">Inhibiting microbial population</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B95">95</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vitro</italic> antimicrobial</td>
<td valign="middle" align="left"><italic>Penicillium funiculosum</italic>
</td>
<td valign="middle" align="left">Inhibiting microbial population</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B96">96</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vitro</italic> antimicrobial</td>
<td valign="middle" align="left"><italic>Candida albicans</italic>
</td>
<td valign="middle" align="left">Disrupting bacteria&#x2019;s regular metabolic processes</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B97">97</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vitro</italic> antimicrobial</td>
<td valign="middle" align="left"><italic>Staphylococcus aureus, Escherichia</italic>
<break/><italic>coli</italic> and <italic>Bacillus subtilis</italic>
</td>
<td valign="middle" align="left">Inhibiting microbial population</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B98">98</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="10" align="left"><bold>Crude garlic extract</bold>
</td>
<td valign="middle" align="left">Allicin</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" rowspan="2" align="left">Human gastric cancer cell lines</td>
<td valign="middle" align="left">Inhibiting cell proliferation through increasing p53 activity and inhibiting Bcl-2 activity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B99">99</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left">DATS</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Blocking cell cycle, decreasing cell viability, through increasing p53 activity and inhibiting Bcl-2 activity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B100">100</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Breast cancer cell</td>
<td valign="middle" align="left">Decreasing cell viability through inhibiting angiogenesis</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B101">101</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">SAC</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Epithelial ovarian cancer cell line</td>
<td valign="middle" align="left">Inhibiting cell growth and inducing cell cycle arrest in the G1/S phase, increasing apoptosis, decreasing cell migration, decreasing pro-caspase-3, Parp-1, and Bcl-2 expression and boosting active caspase-3 and Bax, decreasing Wnt5a expression</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B102">102</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left">SAMC</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Human colorectal cancer cell line (SW620)</td>
<td valign="middle" align="left">Reducing cell viability, cell growth, inducing apoptosis</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B103">103</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Hep3B cancer cell line</td>
<td valign="middle" align="left">Reducing the S phase and extending the G0/G1 phases</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B104">104</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">SPRC</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Pancreatic cancer cells line</td>
<td valign="middle" align="left">Reducing cell viability, cell growth, inducing apoptosis through inducing G2/M-phase and regulating JNK protein level</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B105">105</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Lipophilic compounds</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Hep-G2, Caco-2, PC-3, MCF-7, and TIB-71 cancer cell lines</td>
<td valign="middle" align="left">Decreasing cancer cell viability by 90% on the third day of the experiment</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B106">106</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Ajoene</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Breast cancer cell</td>
<td valign="middle" align="left">Reducing cell viability and cell growth, inducing apoptosis through folding proteins in cancer cell endoplasmic reticulum</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B51">51</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Alliin</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Gastric cancer cell lines</td>
<td valign="middle" align="left">ROS production, mitochondrial membrane potential reduction through Bax/Bcl-2, and cytochrome C upregulation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B99">99</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="5" align="left"><bold>Garlic ethanolic extract</bold>
</td>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vitro</italic> anticancer</td>
<td valign="middle" align="left">Bladder cancer cell</td>
<td valign="middle" align="left">Reducing cell viability, cell growth, inducing apoptosis through Inducing G2/M-phase</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B107">107</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study anti-cancer</td>
<td valign="middle" align="left">Patients treated with chemotherapy for hematologic cancers</td>
<td valign="middle" align="left">Showing protective impact on febrile neutropenia in subgroups with reduced risk</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B108">108</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic> hepatoprotective</td>
<td valign="middle" align="left">Wister rats</td>
<td valign="middle" align="left">Enhancing plasma biochemical markers of liver function, including ALP, AST, urea, and creatinine</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B109">109</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">SAC</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>neuroprotection</td>
<td valign="middle" align="left">Wister rats</td>
<td valign="middle" align="left">Mitigating oxidative stress, neuroinflammatory activity, astrogliosis, and acetylcholinesterase activity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B110">110</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Ajoene</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>neuroprotection</td>
<td valign="middle" align="left">Gerbils</td>
<td valign="middle" align="left">Delaying I/R-induced neuronal death and gliosis in the hippocampus&#x2019;s area through inhibiting lipid peroxidation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B111">111</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="7" align="left"><bold>Black garlic methanolic extract</bold>
</td>
<td valign="middle" rowspan="2" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic> hepatoprotective</td>
<td valign="middle" align="left">Rat hepatocytes</td>
<td valign="middle" align="left">Interfering with oxidative stress, apoptosis, lipid peroxidation, and inflammation Alloxan-induced liver damage attenuation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B112">112</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>antiobesity</td>
<td valign="middle" rowspan="3" align="left">Male rats fed a high-fat diet</td>
<td valign="middle" align="left">Decreasiing the weight and reduce the amount of fat in the retroperitoneal, epididymal, and mesenteric regions.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B113">113</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>antiobesity</td>
<td valign="middle" align="left">Controlling lipid metabolism, reducing weight</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B114">114</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>antiobesity</td>
<td valign="middle" align="left">Mitigating the effect of a high-fat diet on body mass and adipose tissue mass</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B115">115</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">DADS</td>
<td valign="middle" align="left"><italic>In vivo</italic> protection of the digestive system</td>
<td valign="middle" align="left">Small intestine</td>
<td valign="middle" align="left">Facilitating defecation by stimulating gastrointestinal peristalsis and promoting gastrointestinal emptying.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B116">116</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">DAS</td>
<td valign="middle" align="left"><italic>In vitro</italic> protection of the digestive system</td>
<td valign="middle" align="left">Stimulated<break/>intestinal cells</td>
<td valign="middle" align="left">Reducing interferon-induced protein-10 and IL-6 and inhibiting NO and STAT-1 expression.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B117">117</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">DAS</td>
<td valign="middle" align="left"><italic>In vivo</italic> protection of the digestive system</td>
<td valign="middle" align="left">Male ICR mice</td>
<td valign="middle" align="left">Enhancing colitis brought on by dinitro benzenesulfonic acid</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B117">117</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="9" align="left"><bold>Raw garlic</bold>
</td>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study Anti-cancer</td>
<td valign="middle" align="left">17 volunteers</td>
<td valign="middle" align="left">Seven genes are upregulated, including NFAM1, AHR, HIF1A, JUN, ARNT, OSM, and REL.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B118">118</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>antidiabetic</td>
<td valign="middle" align="left">Diabetic rats</td>
<td valign="middle" align="left">Preventing diabetic retinopathy, blood glucose, enhancing weight, and retinal tissue morphological alterations</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B119">119</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study<break/>Antidiabetic</td>
<td valign="middle" align="left">768 type 2 diabetes patients</td>
<td valign="middle" align="left">Producing glycosylated hemoglobin and Fructosamine reduction</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B120">120</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study<break/>Digestive protection and antimicrobial activity</td>
<td valign="middle" align="left"><italic>H. pylori</italic> infected 15 patients</td>
<td valign="middle" align="left">Inhibiting urease activity in bacterial cells, reducing the <italic>Helicobacter pylori</italic> count in the stomach</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B121">121</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Allyl methyl<break/>sulfide</td>
<td valign="middle" align="left"><italic>In vivo</italic> cardiovascular</td>
<td valign="middle" align="left">Diabetic rats</td>
<td valign="middle" align="left">Maintaining cardiac function by inducing the pathway of sirtuin 3-manganese superoxide dismutase.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B122">122</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Allyl methyl<break/>sulfoxide</td>
<td valign="middle" align="left"><italic>In vivo</italic> cardiovascular</td>
<td valign="middle" align="left">Sprague&#x2013;Dawley rats</td>
<td valign="middle" align="left">Reducing the remodeling of myocardial hypertrophy produced by isoproterenol</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B123">123</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left">Cohort study<break/>cardiovascular</td>
<td valign="middle" align="left">30 diabetic patients</td>
<td valign="middle" align="left">Reducing the content of cholesterol LDL and increase the HDL</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B124">124</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Essential oils</td>
<td valign="middle" align="left"><italic>In vivo</italic> immunity</td>
<td valign="middle" align="left">Wister rats</td>
<td valign="middle" align="left">Several immunological indices of rats, such as immunoglobulin and T-cell subtype CD4+, in serum are normalized.</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B125">125</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Polysaccharides</td>
<td valign="middle" align="left"><italic>In vivo</italic> immunity</td>
<td valign="middle" align="left">Broiler (14 days age)</td>
<td valign="middle" align="left">Enhancing lymphocyte multiplication, boosting interferon-&#x3b3; and interleukin-2, and increasing the antibody titer in serum</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B126">126</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="3" align="left"><bold>Aqueous garlic-lemon</bold>
<break/><bold>extract</bold>
</td>
<td valign="middle" align="left">Allicin</td>
<td valign="middle" align="left"><italic>In vivo</italic> anticancer</td>
<td valign="middle" align="left">Female albino mice</td>
<td valign="middle" align="left">Releasing liver injury through glutathione and total protein levels, as well as the elevation of AST, alkaline phosphatase, and alanine aminotransferase levels</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B127">127</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">DADS</td>
<td valign="middle" align="left"><italic>In vivo</italic> anti-cancer</td>
<td valign="middle" align="left">FVB/N mice</td>
<td valign="middle" align="left">Preventing the development of colorectal tumors produced by azoxymethane and dextran sulfate</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B128">128</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">SAMC</td>
<td valign="middle" align="left"><italic>In vivo</italic> anticancer</td>
<td valign="middle" align="left">Hepatoma xenograft model in mice Huh-7 nuclear</td>
<td valign="middle" align="left">Reducing cell viability through cell membrane interaction with the Wnt-pathway co-receptor LRP6</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B104">104</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left"><bold>Garlic-clove extract</bold>
</td>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic> hepatoprotective</td>
<td valign="middle" align="left">Male rabbits</td>
<td valign="middle" align="left">Maintaining the liver cells against CCl<sub>4</sub> injury</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B129">129</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="2" align="left"><bold>LABFGE</bold>
</td>
<td valign="middle" align="left">DADS</td>
<td valign="middle" align="left"><italic>In vivo</italic> hepatoprotective</td>
<td valign="middle" align="left">Wister rats</td>
<td valign="middle" align="left">Reducing fatty liver through a long-term high-fat diet by boosting antioxidants by reducing cytochrome P450 2E1 expression</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B130">130</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Garlic oil</td>
<td valign="middle" align="left"><italic>In vivo</italic> hepatoprotective</td>
<td valign="middle" align="left">1,3-Dichloro-2-propanol-challenged<break/>rats</td>
<td valign="middle" align="left">Increasing antioxidant enzyme activity in the liver, inhibiting the metabolism of 1, 3-dichloro-2-propanol, Reducting liver apoptosis</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B131">131</xref>)</td>
</tr>
<tr>
<td valign="middle" rowspan="3" align="left"><bold>Aqueous garlic extract</bold>
</td>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>renal protection </td>
<td valign="middle" align="left">Diabetic rats</td>
<td valign="middle" align="left">Mitigating oxidative stress in the kidney</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B132">132</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">DATS</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>renal protection </td>
<td valign="middle" align="left">Albino rats</td>
<td valign="middle" align="left">Enhancing the biochemical components in renal plasma mediated by alloxan</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B133">133</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">Group of active compounds</td>
<td valign="middle" align="left"><italic>In vivo</italic>
<break/>renal protection </td>
<td valign="middle" align="left">Wister rats</td>
<td valign="middle" align="left">Mitigating oxidative stress in the kidney induced by As</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B109">109</xref>)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>LABFGE, lactic acid bacteria fermented garlic extract; DAS, diallyl sulfide; DATS, diallyl trisulfide; DADS, diallyl disulfide; SAMC, sallylmercaptocysteine; SAC, S-allyl cysteine; and SPRC, S-propargyl-L-cysteine.</p>
</table-wrap-foot>
</table-wrap>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Biological activities of garlic.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1277074-g002.tif"/>
</fig>
<sec id="s6_1">
<label>6.1</label>
<title>Antimicrobial activity of garlic</title>
<p>The minimum inhibitory concentration (MIC), minimum sensitivity, and minimum bactericidal concentration (MBC) assays are frequently employed to quantify and communicate the antimicrobial properties of garlic and allicin (<xref ref-type="bibr" rid="B134">134</xref>). The antibacterial attributes of allicin found in garlic have been acknowledged for a considerable duration. Extensive research was conducted between 1944 and 1970 on bioeffects of garlic. These studies revealed that garlic extract exhibited exceptional antibacterial properties against Gram-positive and Gram-negative bacteria and specific medically significant fungi (<xref ref-type="bibr" rid="B135">135</xref>, <xref ref-type="bibr" rid="B136">136</xref>). A comprehensive understanding of allicin&#x2019;s antibacterial properties is still elusive; nevertheless, it has been established that it influences the free amino acid L-cysteine by generating allyl-disulfide species (<xref ref-type="bibr" rid="B136">136</xref>). Using the microdilution method, an <italic>in vitro</italic> study examined the antibacterial properties of synthetic allicin against 38 isolates of methicillin-resistant and methicillin-sensitive staphylococci (<xref ref-type="bibr" rid="B137">137</xref>).</p>
<p>Perez-Giraldo et&#xa0;al. (<xref ref-type="bibr" rid="B137">137</xref>) also assessed the effect of allicin on biofilm formation. The outcomes were indistinguishable between methicillin-sensitive and methicillin-resistant bacteria, and it was determined that all cultures examined demonstrated considerable sensitivity to allicin, as indicated by MIC values ranging from 0.25 to 16 mg/L. In an <italic>in vitro</italic> study using five strains of <italic>Staphylococcus epidermidis</italic>, it was reported that adding half the MIC of allicin substantially affected strain proliferation and biofilm formation (<xref ref-type="bibr" rid="B137">137</xref>). According to these findings, allicin might play a beneficial function in preventing the attachment of these microorganisms to medical equipment (<xref ref-type="bibr" rid="B137">137</xref>). The administration of allicin (128 &#xb5;g/mL) substantially impacts the synthesis of extracellular polysaccharide components and their ability to adhere to surfaces, compared to a saline control group (<xref ref-type="bibr" rid="B138">138</xref>).</p>
<p>Allicin is also notable for its ability to prevent the growth of <italic>Pseudomonas aeruginosa</italic> biofilms and the quorum-sensing-regulated generation of virulence components by reducing the expression of specific enzymes and toxins (elastase and exotoxin A) (<xref ref-type="bibr" rid="B139">139</xref>). Thus, allicin may be a viable option for inhibiting the formation and development of <italic>P. aeruginosa</italic> biofilms (<xref ref-type="bibr" rid="B139">139</xref>). Research conducted by Shuford et&#xa0;al. (<xref ref-type="bibr" rid="B140">140</xref>) evaluated the efficacy of garlic extract as an anti-biofilm agent against both the sessile and planktonic strains of <italic>Candida albicans</italic>. They reported that adding fresh aqueous garlic extract may inhibit <italic>C. albicans</italic> biofilm development during the planktonic, adhesive, and sessile phases. Zhai et&#xa0;al. (<xref ref-type="bibr" rid="B141">141</xref>) analyzed the application of allicin with anti-biofilm properties. A scanning electron microscopy investigation into the impact of allicin and vancomycin on the growth of <italic>S. epidermidis</italic> biofilms was identified as the cause of aggregation and biofilm formation (<xref ref-type="bibr" rid="B141">141</xref>). In contrast to the individual effects of allicin and vancomycin, the results demonstrated that the combined effect of the two agents inhibits <italic>S. epidermidis</italic> growth, attachment, and biofilm formation on the outermost layer of a prosthesis (<xref ref-type="bibr" rid="B141">141</xref>).</p>
<p>The potential of garlic and its sulfur constituents as antiviral agents has been demonstrated <italic>in vivo</italic>. Globally speaking, the 2019 coronavirus disease epidemic (COVID-19) is the most critical public health crisis. As a result of the social distancing measures imposed by COVID-19, psychological, financial, and social welfare have undergone substantial transformations in recent years. Lung tissue inflammatory responses and pro-inflammatory pathways (such as IL-6 and IL-1) are primarily activated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic (<xref ref-type="bibr" rid="B142">142</xref>). Viral expression of the angiotensin-converting enzyme 2 (ACE2) receptor can potentially induce harm to critical organs and tissues.</p>
<p>Furthermore, the dysregulation of the ACE2/angiotensin-(1&#x2013;7)/mas axis and the renin-angiotensin system after SARS-CoV-2 infection worsens comorbidities and multi-organ lesions (<xref ref-type="bibr" rid="B143">143</xref>). A cure for the fundamental ailment that has initiated this epidemic remains unknown. Drugs such as hydroxychloroquine, remdesivir, umifenovir, favipiravir, ribavirin, lopinavir/ritonavir, and hydroxychloroquine, among others, may be administered as therapeutic interventions unless explicitly prohibited. In addition to dietary therapy and herbal medication, supportive treatments may effectively prevent the spread of COVID-19 (<xref ref-type="bibr" rid="B142">142</xref>, <xref ref-type="bibr" rid="B143">143</xref>).</p>
<p>Certain foods and herbs contain bioactive substances with antioxidant, antimicrobial, and immunomodulatory properties that may enhance the function and quantity of natural killer cells, macrophages, lymphocytes, and cytokine suppressors (<xref ref-type="bibr" rid="B144">144</xref>). As a result, these substances may aid in pre- and post-exposure prophylaxis. As a result, herbal remedies alleviate the adverse effects of antivirals by reducing the necessary dosage and synergistically improving treatment and outcomes by reducing respiratory symptoms and inflammatory reactions (<xref ref-type="bibr" rid="B144">144</xref>). The numerous health benefits of garlic can be attributed to its sulfur-containing phytochemicals. These include preventing cardiac disease, regulating the immune system, lowering blood sugar levels, combating cancer, and reducing inflammation. The most prevalent sulfur compounds in garlic account for 82% of the total. These include allicin, diallyl (di and tri-) sulfide, ajoenes (E- and Z-ajoene), S-allyl cysteine sulfoxide, and vinyldithiins (2-vinyl-(4H)-1,3-dithiin, 3-vinyl-(4H)-1,2-dithiin). Garlic, apart from alliin, is known to comprise SAC, N-acetylcysteine, and S-allyl-mercapto cysteine, among other organosulfur compounds (<xref ref-type="bibr" rid="B145">145</xref>). Garlic has been found to possess antiviral properties against a range of viruses, including influenza B, HIV (type 1), herpes simplex virus (types 1 and 2), vesicular stomatitis virus, coxsackievirus, and gammaretrovirus (<xref ref-type="bibr" rid="B146">146</xref>).</p>
<p>Recent research has identified the positions of specific amino acids (Thr26, Asn119, Thr24) in the enzyme&#x2019;s active site of the serine-like protease Mpro [chymotrypsin-like protease (3CLpro)] of SARS-primary CoV-2 (e.g., 2GTB and 6 LU7) (<xref ref-type="bibr" rid="B147">147</xref>). A significant degree of structural homology (96.0%) was observed between Mpro from SARS-CoV types 1 and 2. By impeding viral polyprotein cleavage, SARS-CoV-2 infection rates can be significantly diminished because viral polyprotein cleavage is essential for effective protein synthesis and viral replication (<xref ref-type="bibr" rid="B147">147</xref>).</p>
<p>In an <italic>in silico</italic> analysis of the inhibitory activity of garlic, seven onion-specific compounds (OSCs) were identified as resistant to SARS-CoV-2 (<xref ref-type="bibr" rid="B148">148</xref>). These compounds included S-allymercapto-cysteine, S-propyl-L-cysteine, S-(allyl/methyl/ethyl/propyl)-cysteine, and alliin. A molecular docking investigation demonstrated that, among the various cysteine sulphoxides, garlic alliin exhibited the most potent antiviral activity against COVID-19. SARS-CoV-2 could be eradicated by utilizing this bioactive component in isolation or combined with the widely recognized primary treatment medication (<xref ref-type="bibr" rid="B148">148</xref>).</p>
<p>The phytochemicals of black pepper, black cumin, and ginger exhibited a comparable inhibitory effect upon isolation (<xref ref-type="bibr" rid="B148">148</xref>). Garlic clove extract exhibited a significant inhibitory effect on the growth of SARS-CoV-1 <italic>in vivo</italic> at a concentration of 0.1 mL. This effect was likely mediated by the extract&#x2019;s ability to impede the synthesis of genetic material and structural proteins (<xref ref-type="bibr" rid="B149">149</xref>). By inhibiting the protease found in SARS-CoV-1, quercetin might also impede the viral attachment phase of replication (<xref ref-type="bibr" rid="B150">150</xref>). Flavonoids (e.g., quercetin) and organosulfur compounds (e.g., allicin) present in aqueous extracts and essential oils of garlic may account for the decreased viral infection rate induced by SARS-CoV-2 through their interaction with the protease Mpro. Encapsulation is a technique to safeguard bioactive compounds&#x2019; functionality and oxidative stability (<xref ref-type="bibr" rid="B149">149</xref>, <xref ref-type="bibr" rid="B150">150</xref>). Simultaneously, it permits the controlled release and distribution of these compounds to their designated sites of action within the body in the form of medication particles measuring microns or nanometers in size. Finally, to mitigate the transmission of COVID-19 among specific populations, it may be necessary to restrict their intake of foods containing free or encapsulated garlic bioactive ingredients to a moderate degree (<xref ref-type="bibr" rid="B150">150</xref>).</p>
</sec>
<sec id="s6_2">
<label>6.2</label>
<title>The potential anti-inflammatory effects of garlic</title>
<p>Garlic and its derived beneficial components have been found to induce suppression in numerous physiological disorders, such as cardiovascular complications, oxidative stress, cancer proliferation, and immunological dysfunction. NO<sub>2</sub> and prostaglandin E-2 production were suppressed in lipopolysaccharide-stimulated RAW 264.7 macrophages by garlic ethyl linoleate (<xref ref-type="bibr" rid="B83">83</xref>). This was achieved through the downregulation of inducible NO synthase expression and the upregulation of heme oxygenase-1 expression. Garlic&#x2019;s potential utility lies in its ability to augment natural killer cells, stimulate interferon-gamma synthesis, tumor necrosis factor-alpha, and interleukin-2, and counteract the immune response suppression associated with an elevated cancer risk (<xref ref-type="bibr" rid="B151">151</xref>). Furthermore, allicin can potentially mitigate the inflammatory response initiated by schistosome infection in BALB/c rodents, thus establishing itself as a feasible adjuvant therapy (<xref ref-type="bibr" rid="B84">84</xref>).</p>
<p>Furthermore, several research studies have indicated that individuals who are overweight or obese and suffer from osteoarthritis may benefit from garlic supplements as they reduce their resistance (<xref ref-type="bibr" rid="B85">85</xref>). Therefore, garlic effectively inhibited inflammatory pathways in both <italic>in vitro</italic> and <italic>in vivo</italic> investigations through the reduction of inflammatory mediators (including interleukin (IL)-1, tumor necrosis factor-alpha (TNF-&#x3b1;), and NO). Garlic exhibits potential as a therapeutic intervention for inflammatory conditions, including arthritis in humans, since its toxicity is minimal or non-existent (<xref ref-type="bibr" rid="B151">151</xref>). <xref ref-type="fig" rid="f3"><bold>Figure&#xa0;3</bold></xref> depicts the anti-inflammatory effects of garlic.</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>Antiobesity, antidiabetic and anti-inflammatory effects of garlic.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1277074-g003.tif"/>
</fig>
</sec>
<sec id="s6_3">
<label>6.3</label>
<title>Garlic potential as an antioxidant and anticancer agents</title>
<p>According to a growing body of research, garlic exerts potent antioxidant effects. Aged garlic extract possesses greater antioxidant properties than fresh garlic and other available garlic supplements (<xref ref-type="bibr" rid="B28">28</xref>). The antioxidant activity of water-soluble organosulfur compounds such as SAC and SAMC is high. SAC and SAMC are the principal organosulphur components of aged garlic extract (<xref ref-type="bibr" rid="B152">152</xref>). DADS, DAS, and diallyl trisulfide are fat-soluble allyl sulfides with antioxidant potential (<xref ref-type="bibr" rid="B153">153</xref>). Raw garlic showed greater antioxidant activity than cooked garlic, according to a study that examined the antioxidant capabilities of raw and cooked garlic (<xref ref-type="bibr" rid="B154">154</xref>). The antioxidant capacity of stir-fried garlic was also greater (carotene bleaching), indicating that processing may affect the garlic&#x2019;s antioxidant properties (<xref ref-type="bibr" rid="B154">154</xref>).</p>
<p>The ethanolic extract possesses more robust antioxidant activity than raw garlic, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and oxygen radical absorption capacity (ORAC) confirmed these results (<xref ref-type="bibr" rid="B155">155</xref>). Additionally, DPPH, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power, H<sub>2</sub>O<sub>2</sub> scavenging, and Fe<sup>2+</sup> chelating assays revealed that aged garlic extract possessed greater antioxidant properties than fresh garlic (<xref ref-type="bibr" rid="B156">156</xref>). Interestingly, single-clove garlic extract contained a higher concentration of phenolic compounds and exhibited more antioxidant activity than multi-clove garlic extract (<xref ref-type="bibr" rid="B129">129</xref>). In addition, heat treatment improved the antioxidant activity of black garlic, with the peak antioxidant capacity occurring on the 21<sup>st</sup> day of processing (<xref ref-type="bibr" rid="B157">157</xref>, <xref ref-type="bibr" rid="B158">158</xref>). Moreover, the increased pressure enhanced the garlic paste&#x2019;s antioxidant qualities (<xref ref-type="bibr" rid="B159">159</xref>). During fermentation, however, &#x201c;Laba&#x201d; garlic, a traditional Chinese garlic product, loses its antioxidant properties (<xref ref-type="bibr" rid="B160">160</xref>). Garlic saponins have been found to prevent H<sub>2</sub>O<sub>2</sub>-induced growth inhibition and DNA damage in C<sub>2</sub>C<sub>12</sub> myoblasts generated from mice (<xref ref-type="bibr" rid="B78">78</xref>).</p>
<p>Garlic and its active constituents (phenols and saponins) are antioxidants (<xref ref-type="bibr" rid="B161">161</xref>). Various processing procedures also modulated the antioxidant activity of garlic (<xref ref-type="bibr" rid="B45">45</xref>). The antioxidant activity of raw garlic was greater than that of cooked garlic, and the antioxidant activity of raw garlic was more than that of cooked garlic (<xref ref-type="bibr" rid="B154">154</xref>). The potency of fermented garlic, such as black garlic, is greater than that of raw garlic (<xref ref-type="bibr" rid="B162">162</xref>). In addition, the cellular experiment demonstrated that the mechanism of garlic&#x2019;s antioxidative effect might include the modulation of the Nrf-2-ARE pathway and the augmentation of antioxidant enzyme activity (<xref ref-type="bibr" rid="B78">78</xref>).</p>
<p>Even though cancer is a significant contributor to mortality worldwide, several spices and foods including ginger, berries, tomatoes, and cruciferous vegetables have been shown to possess potent anticancer properties (<xref ref-type="bibr" rid="B163">163</xref>). Recent research has demonstrated that garlic and its bioactive constituents inhibit the development of numerous types of cancer, including those of the gastrointestinal tract, colon, lungs, and urinary tract (<xref ref-type="bibr" rid="B102">102</xref>). Daily, individuals frequently encounter numerous carcinogenic substances (<xref ref-type="bibr" rid="B164">164</xref>). According to an <italic>in vitro</italic> study, garlic&#x2019;s sulfur-containing compounds inhibited the activation of cancer-causing substances (<xref ref-type="bibr" rid="B165">165</xref>). Furthermore, the production of nitrosamines, typical carcinogens generated during heating and storage, could be inhibited by garlic and the organic allyl sulfides it produces (<xref ref-type="bibr" rid="B166">166</xref>).</p>
<p>Furthermore, the allyl sulfides in garlic inhibit DNA alkylation, an early step in developing nitrosamine carcinogenesis (<xref ref-type="bibr" rid="B167">167</xref>). Cancer cells are primarily characterized by their uncontrolled proliferation, a distinctive feature of the ailment. Previous studies (<xref ref-type="bibr" rid="B168">168</xref>) have documented the high sensitivity of various human cancer cell lines to the antiproliferative effects of unrefined garlic extract, including colon (Caco-2), prostate (PC-3), breast (MCF-7), and liver (HepG2) cancer cells (<xref ref-type="bibr" rid="B168">168</xref>). By inhibiting the phosphorylation of Cdc25C and Cdc2, they are increasing the expression of p21WAF1 and decreasing the phosphorylation of Cyclin B1 (<xref ref-type="bibr" rid="B168">168</xref>, <xref ref-type="bibr" rid="B169">169</xref>). Garlic extract (<xref ref-type="bibr" rid="B107">107</xref>, <xref ref-type="bibr" rid="B170">170</xref>) improved checkpoint kinase two and G2/M-phase cell modification. Research has demonstrated that whether in its unprocessed or ground state, garlic can upregulate the activity of apoptosis-related genes, including hypoxia-inducible factor 1, proto-oncogene c-jun, and aryl hydrocarbon receptor (<xref ref-type="bibr" rid="B118">118</xref>, <xref ref-type="bibr" rid="B171">171</xref>).</p>
<p>Additionally, the aged garlic extract inhibited the motility, development, and tube formation of ECV304 endothelial cells, altering the cellular composition of rat lungs (<xref ref-type="bibr" rid="B79">79</xref>). Therefore, garlic and its bioactive constituents have the potential to serve as a beneficial strategy in the prevention and management of specific types of cancer (<xref ref-type="bibr" rid="B172">172</xref>, <xref ref-type="bibr" rid="B173">173</xref>). Primary anticancer strategies include initiating apoptosis, inhibiting the growth and division of cancer cells, regulating the metabolism of carcinogenic agents, limiting the formation of new blood vessels, and minimizing invasion and metastasis (<xref ref-type="bibr" rid="B174">174</xref>, <xref ref-type="bibr" rid="B175">175</xref>).</p>
<p>
<xref ref-type="fig" rid="f4"><bold>Figure&#xa0;4</bold></xref> illustrates the process by which garlic&#x2019;s bioactive components inhibit the growth of cancer cells.</p>
<fig id="f4" position="float">
<label>Figure&#xa0;4</label>
<caption>
<p>The anticancer mechanisms of garlic-derived phytochemicals.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1277074-g004.tif"/>
</fig>
</sec>
<sec id="s6_4">
<label>6.4</label>
<title>The potential immunomodulatory effects of garlic</title>
<p>Garlic and its derived bioactive constituents, including organosulfur compounds, may enhance immune system performance via pathways such as oxidative stress, interleukins, immunological and inflammatory response, and others, according to numerous <italic>in vitro</italic> and <italic>in vivo</italic> experimental studies (<xref ref-type="bibr" rid="B176">176</xref>). Upon exposure to polysaccharides derived from garlic, RAW 264.7 macrophages exhibit distinct variations in tumor necrosis factor-&#x3b1;, IL-10, IL-6, and interferon-&#x3b3; expression. These polysaccharides possess notable immunomodulatory properties (<xref ref-type="bibr" rid="B177">177</xref>).</p>
<p>Fresh garlic polysaccharides exhibit a more pronounced immunomodulatory impact than black garlic polysaccharides (<xref ref-type="bibr" rid="B93">93</xref>). This effect results from fructan degradation associated with the process (<xref ref-type="bibr" rid="B177">177</xref>). In an <italic>in vivo</italic> study, Li et&#xa0;al. (<xref ref-type="bibr" rid="B177">177</xref>) showed that by administering garlic oil to Wistar rats 30 min before diazinon, a range of immunological parameters were restored to normalcy. These parameters included the serum total immunoglobulin level and T-cell subtype CD4+. Additionally, research has demonstrated that administering aged garlic extract to individuals may reduce the severity of specific viral infections, such as the common cold, and strengthen the immune system (<xref ref-type="bibr" rid="B93">93</xref>). This indicates that garlic&#x2019;s primary immune-modulating components are polysaccharides (<xref ref-type="bibr" rid="B93">93</xref>).</p>
</sec>
</sec>
<sec id="s7">
<label>7</label>
<title>Therapeutical application of bioactive compounds in garlic</title>
<sec id="s7_1">
<label>7.1</label>
<title>Anti-hypertensive function</title>
<p>Garlic may decrease oxidative stress, inhibit the angiotensin-converting enzyme, and increase the production of NO and H<sub>2</sub>S, all of which contribute to blood pressure reduction (<xref ref-type="bibr" rid="B178">178</xref>, <xref ref-type="bibr" rid="B179">179</xref>). By increasing NO production, aged garlic extract induced endothelial-dependent vasodilation in individual rat aortic rings, according to one study. Moreover, L-arginine was crucial for NOS-mediated NO production in aged garlic extract (<xref ref-type="bibr" rid="B178">178</xref>). Additionally, it was demonstrated that S-1-propylene cysteine was the principal antihypertensive component in the aged garlic extract. It was demonstrated that administration of S-1-propylenecysteine decreased the systolic blood pressure of rats with spontaneous hypertension but had no effect on control rats (<xref ref-type="bibr" rid="B180">180</xref>). In an additional investigation, nitrites present in fermented garlic extract (FGE) were metabolized to NO through the action of <italic>Bacillus subtilis</italic> (<xref ref-type="bibr" rid="B180">180</xref>).</p>
<p>Furthermore, NO decreased systolic blood pressure in rodents with spontaneous hypertension via the protein kinase G (PKG)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway (<xref ref-type="bibr" rid="B181">181</xref>). By downregulating vascular endothelial cell adhesion molecule-1 and matrix metalloproteinase-9 (MMP-9) and upregulating PKG and endothelial nitric oxide synthase (eNOS), FGE decreased blood pressure in rats with pulmonary hypertension induced by monocrotaline (<xref ref-type="bibr" rid="B181">181</xref>). Furthermore, the efficacy of captopril in reducing hypertension and angiotensin-converting enzyme (ACE) in rodents was improved through the combination of captopril with garlic and its bioactive component, alliin (<xref ref-type="bibr" rid="B182">182</xref>). Systolic and diastolic blood pressures of 44 hypertensive participants registered for a double-blind, placebo-controlled study experienced a substantial reduction when garlic was prepared with enzymatic browning (<xref ref-type="bibr" rid="B183">183</xref>).</p>
</sec>
<sec id="s7_2">
<label>7.2</label>
<title>The impact of garlic on kidney and liver functions</title>
<p>Recent <italic>in vivo</italic> studies have demonstrated garlic&#x2019;s effective reduction of nephrotoxicity (<xref ref-type="bibr" rid="B184">184</xref>). After being exposed to garlic&#x2019;s aqueous component, the kidneys of diabetic rats showed a reduction in oxidative stress (<xref ref-type="bibr" rid="B132">132</xref>). In addition, the water-based element of garlic improved the levels of renal plasma biochemical markers in Wistar rat models that were affected by alloxan (<xref ref-type="bibr" rid="B109">109</xref>). In addition, studies have shown that diallyl trisulfide can activate the Nrf2-ARE pathway in rats, which helps protect kidney tissue from oxidative stress caused by arsenic (<xref ref-type="bibr" rid="B174">174</xref>).</p>
<p>Numerous studies have indicated that various natural compounds, such as garlic, can positively impact liver function (<xref ref-type="bibr" rid="B185">185</xref>). In an <italic>in vivo</italic> study, researchers discovered that a natural extract derived from black garlic significantly reduced the harmful effects of tert-butyl hydroperoxide on rat clone-9 hepatocytes (<xref ref-type="bibr" rid="B112">112</xref>). This extract effectively countered oxidative stress, lipid peroxidation, inflammation, and apoptosis, showcasing its potential as a valuable therapeutic agent. Ascorbic acid and garlic effectively prevented liver damage caused by Cd in an albino mouse model (<xref ref-type="bibr" rid="B112">112</xref>). An <italic>in vivo</italic> study using a male rabbit model found that a single clove of garlic provided more excellent protection against acute liver damage induced by CCl<sub>4</sub> compared to multiple cloves of garlic (<xref ref-type="bibr" rid="B129">129</xref>).</p>
<p>Furthermore, it has been proposed that the active compounds found in garlic, specifically S-methyl-l-cysteine, DADS, and DAS may have potential applications in treating and preventing liver damage caused by ethanol. A study found that DADS in garlic essential oil reduced the effects of nonalcoholic fatty liver disease caused by a high-fat diet in rats (<xref ref-type="bibr" rid="B186">186</xref>). Through its effects on cytochrome P450 2E1, DADS enhanced antioxidant capacity and decreased pro-inflammatory cytokine production in liver tissue (<xref ref-type="bibr" rid="B186">186</xref>). Lai et&#xa0;al. (<xref ref-type="bibr" rid="B130">130</xref>) reported that fermented garlic extract, shows potential as a treatment for chronic hepatic diseases (<xref ref-type="bibr" rid="B130">130</xref>).</p>
<p>In a study by Kim et&#xa0;al. (<xref ref-type="bibr" rid="B187">187</xref>), a randomized, double-blind, placebo-controlled trial was conducted to examine the impact of fermented garlic extract on hepatic activity in 36 individuals with moderately elevated blood gamma-glutamyl transpeptidase concentrations. Based on the results, no unexpected outcomes were linked to the increased alanine aminotransferase levels and gamma-glutamyl transpeptidase. Therefore, garlic has the potential to treat either condition effectively.</p>
</sec>
<sec id="s7_3">
<label>7.3</label>
<title>The impact of garlic on the digestive system</title>
<p>Garlic has been extensively studied for its positive impact on digestive processes. In a study conducted in a laboratory setting, it was found that black garlic extract has the potential to enhance bowel movements. This is achieved by promoting bowel emptying and stimulating peristaltic action. An <italic>in vitro</italic> study found that the aquatic fraction of black garlic had a more significant impact on improving gastrointestinal function in the small intestine than the n-butanol and ethyl acetate mixture (<xref ref-type="bibr" rid="B116">116</xref>). Additionally, therapy involving cabbage and garlic extract showed a decrease in the severity of gastric ulcers and a reduction in gastric juice volume, stomach acid levels, microbial count, and histological alterations. This type of treatment improved stomach acidity in rat models (<xref ref-type="bibr" rid="B188">188</xref>).</p>
<p><italic>In vivo</italic> rat models, aged garlic extract effectively reduced the development of ulcers caused by indomethacin. This was achieved by increasing the levels of prostaglandin E-2 and glutathione while also reducing oxidative stress in the stomach tissue of the rats (<xref ref-type="bibr" rid="B90">90</xref>). Like a pharmacologist, DADS was found to suppress the expression of signal transducer and transcription 1 (STAT-1) activator in interferon-induced intestinal cells (<xref ref-type="bibr" rid="B117">117</xref>).</p>
<p>Additionally, DAS was observed to suppress the expression of interferon-inducible protein-10, interleukin-6, and nitric oxide. In a mouse model, the colitis caused by dinitrobenzene sulfonic acid was made worse by including DAS and DADS (<xref ref-type="bibr" rid="B117">117</xref>). Raw garlic has been shown to positively impact microbial urease function and <italic>Helicobacter pylori</italic> levels in the stomachs of patients (<xref ref-type="bibr" rid="B121">121</xref>).</p>
</sec>
<sec id="s7_4">
<label>7.4</label>
<title>The impact of garlic on cardiovascular functioning</title>
<p>In recent years, there has been a significant increase in the death rate from cardiovascular illnesses (<xref ref-type="bibr" rid="B189">189</xref>). There has been a recent surge in interest in utilizing natural crops to support optimal heart health, and garlic stands out as one of the most promising choices (<xref ref-type="bibr" rid="B190">190</xref>). Eating garlic powder has been shown to reduce several risk factors for cardiovascular disease, including total cholesterol, blood pressure, and low-density lipoprotein cholesterol (<xref ref-type="bibr" rid="B191">191</xref>).</p>
<p>Garlic has the potential to offer various health benefits in this field. These include an increase in the production of NO and H<sub>2</sub>S, a reduction in oxidative stress, and the ability to inhibit the angiotensin-converting enzyme, which can help lower blood pressure (<xref ref-type="bibr" rid="B117">117</xref>). Research conducted by Takashima et&#xa0;al. (<xref ref-type="bibr" rid="B178">178</xref>) suggests that aged garlic extract may have the potential to stimulate NO synthesis and promote endothelial-dependent vasodilation in the aortic rings of rats. It was found that the L-arginine in aged garlic extract plays a crucial role in NOS-mediated NO production (<xref ref-type="bibr" rid="B117">117</xref>).</p>
<p>Garlic has the potential to support the maintenance of the heart. Garlic when combined with allicin, the rat model showed enhanced antihypertensive and ACE-lowering effects of captopril (<xref ref-type="bibr" rid="B182">182</xref>). In an animal model of insulin resistance and obesity, garlic extract effectively reduced cardiac and mitochondrial dysfunction (<xref ref-type="bibr" rid="B192">192</xref>). When allicin comes into contact with thiols, it transforms organic diallyl polysulfide. This compound plays a crucial role in supplying H<sub>2</sub>S to support the proper functioning of the heart (<xref ref-type="bibr" rid="B193">193</xref>). Given these discoveries, garlic has been the focus of numerous clinical trials exploring its potential in treating hyperlipidemia, hypertension, and cardiovascular disease. Garlic may exert its effects through various mechanisms, including modulation of NO and H<sub>2</sub>S production, reduction of oxidative stress, and inhibition of angiotensin-converting enzyme activity (<xref ref-type="bibr" rid="B193">193</xref>).</p>
</sec>
<sec id="s7_5">
<label>7.5</label>
<title>Anti-diabetic activity</title>
<p>Regarding diabetes, garlic prevented pancreatic cell damage and associated pathological alterations (<xref ref-type="bibr" rid="B194">194</xref>). Moreover, diabetes-linked retinopathy risk was significantly reduced through garlic (<xref ref-type="bibr" rid="B195">195</xref>). Al-Brakati (<xref ref-type="bibr" rid="B119">119</xref>) addressed significant improvement in retinal tissue after seven weeks of oral administration of raw garlic. Moreover, Thomson et&#xa0;al. (<xref ref-type="bibr" rid="B196">196</xref>) noticed the favorable modulatory effect of garlic on body weight and blood glucose level. Aged garlic extract pointed out that antidiabetic behavior correlated with dosage (<xref ref-type="bibr" rid="B196">196</xref>). Garlic supplements showed reduced fructosamine and glycosylated hemoglobin in type 2 diabetes patients (<xref ref-type="bibr" rid="B174">174</xref>). Consistently, garlic has shown potential in treating type 2 diabetes (<xref ref-type="bibr" rid="B197">197</xref>). In conclusion, garlic can be a candidate for protecting and treating diabetes and diabetic disorders (<xref ref-type="bibr" rid="B198">198</xref>). <xref ref-type="fig" rid="f3"><bold>Figure&#xa0;3</bold></xref> depicts the antidiabetic benefits of garlic.</p>
</sec>
<sec id="s7_6">
<label>7.6</label>
<title>Anti-obesity activity</title>
<p>Garlic and sulfur-containing compounds can help lose weight by inhibiting 3T3-L1 adipocytes and acetyl-CoA carboxylase (ACC-1) (<xref ref-type="bibr" rid="B120">120</xref>, <xref ref-type="bibr" rid="B199">199</xref>). Lee et&#xa0;al. (<xref ref-type="bibr" rid="B200">200</xref>) addressed an activation in adenosine monophosphate-activated protein kinase (AMPK)I in addition to carnitine palmitoyl transferase (CPT-1). Consistently (<xref ref-type="bibr" rid="B201">201</xref>), found an increase in UCP-1 through Kruppel-like factor 15 (KLF15), linked to brown adipocytes that represent a crucial phenotype for protection against obesity. Furthermore, in the diet-induced obesity model, fermented garlic (250 and 500 mg/kg) revealed lowered body weight with underlying decreased cholesterol levels. Garlic oil reduced body weight and white adipose tissue quantity in the high-fat diet model (<xref ref-type="bibr" rid="B201">201</xref>). El-Demerdash et&#xa0;al. (<xref ref-type="bibr" rid="B202">202</xref>) observed an improved O<sub>2</sub> consumption during the night with interesting increased energy expenditure during the daytime. Similarly, garlic extract in water was linked to hypoglycemic impact (<xref ref-type="bibr" rid="B202">202</xref>).</p>
<p>Sanie-Jahromi et&#xa0;al. (<xref ref-type="bibr" rid="B203">203</xref>) noted significant hypoglycemic impact among garlic compounds, alliin, allyl sulfide, and glibenclamide (<xref ref-type="bibr" rid="B203">203</xref>). Garlic oil (10 mg/kg i.p.) and diallyl trisulfides promoted both sensitivity and secretion of insulin in diabetic rat models (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B202">202</xref>, <xref ref-type="bibr" rid="B204">204</xref>). In high-fat diet mice, lactic acid bacteria fermented garlic extract (LABFGE) showed an anti-obesity property with significantly decreased body weight and adipose tissue (<xref ref-type="bibr" rid="B113">113</xref>). LABFGE's ability to reduce lipogenesis is attributed to a decrease in the expression of lipogenic proteins (<xref ref-type="bibr" rid="B113">113</xref>). Methanolic extract of black garlic (MEBG) reversed the weight gain of a high-fat diet (<xref ref-type="bibr" rid="B205">205</xref>). MEBG modulated the network of adipogenesis, adipokine biosynthesis, and lipolysis, such as upregulation of AMPK, FOXO1, and adiponectin, whereas MEBG downregulated CD36 and TNF-&#x3b1; in HFD rats (<xref ref-type="bibr" rid="B115">115</xref>). Therefore, we could address that garlic and garlic-derived compounds have a potential role as anti-obesity and can reduce lipogenesis. The anti-obesity properties of garlic are illustrated in <xref ref-type="fig" rid="f3"><bold>Figure&#xa0;3</bold></xref>.</p>
</sec>
<sec id="s7_7">
<label>7.7</label>
<title>Cardiovascular and neuroprotection</title>
<p>In recent years, cardiovascular disease has been the leading cause of fatality (<xref ref-type="bibr" rid="B190">190</xref>, <xref ref-type="bibr" rid="B191">191</xref>). Recently, interest in using natural crops to support cardiac health has increased, and garlic is among the most promising candidates (<xref ref-type="bibr" rid="B190">190</xref>). Several cardiovascular disease risk factors, including low-density lipoprotein cholesterol, total cholesterol, and blood pressure, are reduced by consuming garlic powder (<xref ref-type="bibr" rid="B194">194</xref>). Potential prospective health benefits of garlic in this domain include the following: (1) increased production of NO and H<sub>2</sub>S; (2) reduced oxidative stress; and (3) inhibition of the angiotensin-converting enzyme, which ultimately results in reduced blood pressure (<xref ref-type="bibr" rid="B117">117</xref>).</p>
<p>Takashima et&#xa0;al. (<xref ref-type="bibr" rid="B178">178</xref>) conducted research suggesting that administering matured garlic extract to rodents could induce endothelial-dependent vasodilation in the aortic rings by stimulating NO synthesis. In addition, the L-arginine in aged garlic extract was found to be crucial for NOS-mediated NO production (<xref ref-type="bibr" rid="B178">178</xref>). Furthermore, adding garlic and allicin enhanced captopril&#x2019;s antihypertensive and ACE-lowering effects in the rodent model (<xref ref-type="bibr" rid="B182">182</xref>). An additional organ that garlic may aid in maintaining is the heart. Cardiovascular and mitochondrial dysfunction were mitigated by garlic extract in an animal model of obesity and insulin resistance (<xref ref-type="bibr" rid="B192">192</xref>). Allicin was readily converted to organic diallyl polysulfide upon exposure to thiols; this compound supplied H<sub>2</sub>S to sustain the heart&#x2019;s activity (<xref ref-type="bibr" rid="B203">203</xref>). In light of these findings, garlic has been the subject of numerous clinical trials regarding its potential to treat hyperlipidemia, hypertension, and cardiovascular diseases (<xref ref-type="bibr" rid="B203">203</xref>). Potential principal mechanisms of action for garlic include alterations in the production of NO and H<sub>2</sub>S, a reduction in oxidative stress, and a decrease in the activity of angiotensin-converting enzyme (<xref ref-type="bibr" rid="B203">203</xref>).</p>
<p>It was reported that an aged garlic extract-carbohydrate derivative, N-&#x3b1;-(1-deoxy-D-fructos-1-yl)-L-arginine, could reduce neurological inflammation in a mouse model of BV-2 microglial cells activated lipopolysaccharide by regulating the expression of numerous oxidative stress-related protein targets and inhibiting NO production (<xref ref-type="bibr" rid="B192">192</xref>, <xref ref-type="bibr" rid="B193">193</xref>). Ho and Su (<xref ref-type="bibr" rid="B206">206</xref>) suggested that the anti-neuritis effect of garlic against lipopolysaccharide-activated BV-2 microglial cells (<xref ref-type="bibr" rid="B206">206</xref>) was due to its organosulfur components. Supplementation with garlic in pregnant and lactating rats reduced blood and brain Pb concentrations and prevented Pb-induced neuronal loss during hippocampal development (<xref ref-type="bibr" rid="B207">207</xref>).</p>
<p>Utilizing the Basso, Beattie, and Bresnahan (BBB) scoring system, the neurological impact of aging on a spinal cord I/R model of rats was evaluated (<xref ref-type="bibr" rid="B208">208</xref>). Significantly higher BBB scores were observed in the aged garlic extract group compared to the I/R group, suggesting that aged garlic extract exerted a substantial neuroprotective effect. Aged garlic extract also increased levels of glutamate decarboxylase and vesicular glutamate transporter 1 in the hippocampus, which enhanced working memory in rodents, additionally, it reduced the loss of cholinergic neurons (<xref ref-type="bibr" rid="B208">208</xref>).</p>
<p>Furthermore, research has demonstrated that a garlic ethanol extract can enhance memory (<xref ref-type="bibr" rid="B88">88</xref>). Garlic treatment increased the concentrations of Na<sup>+</sup>/K<sup>+</sup> ATPase, Ca<sup>2+</sup> ATPase, and glutamine synthetase in the brains of diabetic Wistar rats (<xref ref-type="bibr" rid="B209">209</xref>). In addition, the detrimental effects of monosodium glutamate on working memory were effectively counterbalanced by the fermented garlic ethanol extract (<xref ref-type="bibr" rid="B210">210</xref>). Z-ajoene has demonstrated advantageous effects in the CA1 region of the hippocampus by decreasing lipid peroxidation and mitigating delayed neuronal mortality and gliosis induced by I/R stimulation (<xref ref-type="bibr" rid="B111">111</xref>). SAC ameliorated rat cognitive impairment due to reduced acetylcholinesterase activity, neuroinflammation, astrogliosis, and oxidative stress (<xref ref-type="bibr" rid="B110">110</xref>). The neuroprotective effects of garlic primarily target the hippocampus, as demonstrated by both <italic>in vivo</italic> and <italic>in vitro</italic> studies. Substantial evidence indicates that organic sulfur compounds play a vital function in protecting neurons (<xref ref-type="bibr" rid="B110">110</xref>). The neuroprotective properties of garlic are illustrated in <xref ref-type="fig" rid="f5"><bold>Figure&#xa0;5</bold></xref>.</p>
<fig id="f5" position="float">
<label>Figure&#xa0;5</label>
<caption>
<p>The neuroprotective properties of garlic. All lables <bold>(A&#x2013;G)</bold> are the sequence of events/properties of garlic toward neuroprotection.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fimmu-15-1277074-g005.tif"/>
</fig>
</sec>
</sec>
<sec id="s8">
<label>8</label>
<title>Safety of garlic bioactive compounds and their derivatives</title>
<sec id="s8_1">
<label>8.1</label>
<title>Suggested dosage</title>
<p>The elderly are advised to consume four grams of fresh garlic, seven and a half grams of matured garlic extract, or one dried garlic powder tablet three or four times daily (<xref ref-type="bibr" rid="B211">211</xref>). In their study, Rana et&#xa0;al. (<xref ref-type="bibr" rid="B212">212</xref>) demonstrated that administering garlic orally or intraperitoneally to rats at a 50 mg/kg dose had no discernible impact on liver and lung tissue. However, rats consuming garlic daily at doses of 250, 500, and 1000 mg/kg developed acute alterations in liver and lung tissue, indicating the presence of dose-dependent toxicity (<xref ref-type="bibr" rid="B212">212</xref>). Upon light microscopy and ultrastructural analysis, morphological abnormalities in the liver were observed at a daily dosage of 1000 mg/kg garlic. In contrast, auto-antioxidant levels were significantly reduced at 500 and 1000 mg/kg garlic concentrations without affecting lipid peroxidation levels. Histological analysis further demonstrated the presence of nonspecific focal injury on hepatocytes (<xref ref-type="bibr" rid="B212">212</xref>).</p>
<p>A study by Mikaili et&#xa0;al. (<xref ref-type="bibr" rid="B213">213</xref>) demonstrated that biological and histological markers in male and female rodents were altered, and development was halted at 300 and 600 mg of garlic bulb extract. Asdaq and Inamdar (<xref ref-type="bibr" rid="B214">214</xref>) showed that the combination of 250 mg/kg of garlic and hydrochlorothiazide offers cardioprotective and synergistic effects against fructose and isoproterenol toxicity. Antioxidant enzyme activity was substantially increased in the presence of propranolol and 250 mg/kg garlic during ischemia-induced injury (<xref ref-type="bibr" rid="B214">214</xref>).</p>
</sec>
<sec id="s8_2">
<label>8.2</label>
<title>Hazards and adverse reactions</title>
<p>The US Food and Drug Administration (FDA) has determined that garlic is safe for human consumption; however, sensitive stomachs may experience distress when consuming large quantities of garlic. Randomized controlled trials examining the safety of garlic documented the following adverse effects: insomnia, dizziness, emesis, tachycardia, headache, flushing, mild orthostatic hypotension, sweat, discomfort, foul body odor, and defecation (<xref ref-type="bibr" rid="B212">212</xref>). When consumed in excess on an empty stomach, fresh garlic can cause intestinal flora to shift, flatulence, and bloating. The topical application of fresh garlic also led to the development of excruciating lesions, rashes, and burns (<xref ref-type="bibr" rid="B215">215</xref>).</p>
<p>In contrast to the prevailing notion that garlic does not affect medication metabolism, recent studies involving healthy volunteers indicated that its antithrombotic properties might result in an inconsistent effect of garlic on the pharmacokinetics of anticoagulants and protease inhibitors (<xref ref-type="bibr" rid="B216">216</xref>). As it has been shown to prolong bleeding in one individual with an epidural spontaneous hematoma, many surgeons advise against consuming large quantities of garlic 7&#x2013;10 days before surgery (<xref ref-type="bibr" rid="B216">216</xref>).</p>
<p>Long-term, high-dose exposure to raw garlic in animals results in anemia and weight loss due to the lysis of red blood cells (RBCs), whereas 5 mL/kg of raw garlic liquid injected into animals induces gastrointestinal damage and mortality. Spermatogenesis is inhibited in rodents when 50 milligrams of garlic powder are administered daily for an extended period (<xref ref-type="bibr" rid="B212">212</xref>). This results in decreased sialic acid levels in the testes, the bladder, and seminal vesicles and decreased Leydig cell activity (<xref ref-type="bibr" rid="B212">212</xref>). As evidenced by the formation of Heinz bodies in RBCs and the development of methemoglobinemia, oxidative hemolysis is the principal toxicological mechanism by which sulfur compounds derived from <italic>Allium</italic> (<xref ref-type="bibr" rid="B217">217</xref>). Initial clinical manifestations included depression, appetite loss, vomiting, abdominal discomfort, anemia manifested by pallid mucous membranes, diarrhea, jaundice, lethargy, accelerated heart and respiratory rates, and hemoglobinuria (<xref ref-type="bibr" rid="B218">218</xref>). The onset of symptoms associated with garlic poisoning can vary significantly, spanning from one day to several weeks following ingestion (<xref ref-type="bibr" rid="B218">218</xref>).</p>
<p>Anticoagulant and fibrinolytic properties, in addition to a significant decrease in platelet production and conflicting effects on fibrinolytic effectiveness, have been documented in garlic, as reported in prior studies (<xref ref-type="bibr" rid="B219">219</xref>). Upon oral ingestion, dehydrated raw garlic powder damages the stomach mucosa promptly, as demonstrated by Chen et&#xa0;al. (<xref ref-type="bibr" rid="B220">220</xref>). However, experimental mice&#x2019;s intestinal mucosa is protected by the sulfur-free compound aged garlic extract, as reported by Y&#xfc;nc&#xfc; et&#xa0;al. (<xref ref-type="bibr" rid="B221">221</xref>). Research studies have established that while garlic is deemed safe when consumed in moderation amounts, therapeutic doses may induce gastrointestinal distress, and excessive quantities have been linked to liver harm (<xref ref-type="bibr" rid="B188">188</xref>). Allicin&#x2019;s potential toxicity could be attributed to its capacity to traverse cellular membranes and interact with cellular thiols, such as glutathione or cysteine residues in proteins (<xref ref-type="bibr" rid="B132">132</xref>), as well as enzymes incorporating reactive cysteine (<xref ref-type="bibr" rid="B222">222</xref>). Rana et&#xa0;al. (<xref ref-type="bibr" rid="B212">212</xref>) discovered that allicin or garlic powder at a concentration of 200 mg/mL could potentially cause severe cell injury in the livers of isolated rats (<xref ref-type="bibr" rid="B212">212</xref>).</p>
</sec>
</sec>
<sec id="s9">
<label>9</label>
<title>Food application of garlic bioactive compounds and their derivatives</title>
<p>Food illness and decay may result from pathogenic bacteria or other microorganisms. Antibiotics are frequently employed in the fight against these microorganisms. Antioxidants are gaining popularity as a method of preventing nutrient losses and extending the storage life of foods by preventing oxidation. However, excessive antibiotic use may lead to the emergence of antibiotic resistance (<xref ref-type="bibr" rid="B142">142</xref>). The majority of artificial antimicrobial agents authorized for use as food preservatives by regulatory bodies, based on studies conducted by Guti&#xe9;rrez-del-Ro et&#xa0;al. (<xref ref-type="bibr" rid="B223">223</xref>), pose a risk to consumer health.</p>
<p>Sulfites, a class of thiol compounds used as commercial food preservatives, have been associated with numerous adverse nutritional effects, including ingesting thiamine, commonly referred to as vitamin B1. Therefore, preservatives derived from naturally generated antimicrobial compounds discovered in microorganisms, plants, and animals are widely employed. Antimicrobials prevent the spoilage of food and impede the transmission of disease (<xref ref-type="bibr" rid="B224">224</xref>).</p>
<p>Many individuals use natural and safer preservatives to impart an &#x201c;organic&#x201d; or &#x201c;green&#x201d; appearance to their food. Investigations have been directed toward the potential use of essential oils derived from botanicals as food preservatives (<xref ref-type="bibr" rid="B225">225</xref>). Garlic in food storage extends the expiration life by six days when refrigerated and slows the rate of food spoilage caused by microorganisms, according to recent studies (<xref ref-type="bibr" rid="B226">226</xref>). The utilization of garlic paste extended the freshness of Nile tilapia by over three days, according to research conducted by Kombat et&#xa0;al. (<xref ref-type="bibr" rid="B227">227</xref>).</p>
<p>Research on extending the shelf life of ready-to-eat (RTE) products has primarily focused on utilizing natural organic essential oils (EOs) and coatings. The extraction of plants EOs results in low harvests and high costs (<xref ref-type="bibr" rid="B228">228</xref>, <xref ref-type="bibr" rid="B229">229</xref>). Therefore, in culinary applications, plant aqueous extracts may function as acceptable alternatives to natural essential oils (<xref ref-type="bibr" rid="B230">230</xref>). Diao et&#xa0;al. (<xref ref-type="bibr" rid="B231">231</xref>) investigated the preservation effect of carboxymethyl chitosan (CMCS) ultrasonicated coating modified with garlic aqueous extracts on RTE fragrant poultry. By employing ultrasonic processing, CMCS, and garlic aqueous extracts were transformed into a rudimentary nano-coating solution that satisfies the safety requirements for human consumption. Utilizing the ultrasonicated coating method devised with garlic aqueous extracts-CMCS may be advantageous for RTE poultry meat (<xref ref-type="bibr" rid="B231">231</xref>).</p>
<p>Garlic essential oil derives its antibacterial properties from its substantial concentration of organosulfur compounds. Primarily present in garlic essential oil, allicin is susceptible to degradation when exposed to acidity and temperature shocks. Encapsulation may enhance the stability and solubility of the substance in water-based foods. Additionally, encapsulation obscures the foul, pungent odor of pure garlic EOs (<xref ref-type="bibr" rid="B232">232</xref>). A bioactive component in liquid, solid, or gaseous state is encapsulated within a matrix of inert material via nanoencapsulation to maintain coated items. Nanoencapsulation can potentially enhance the sensory attributes of products through the augmentation of bioactive chemical stability and the obfuscation of offensive flavors and aromas (<xref ref-type="bibr" rid="B233">233</xref>).</p>
<p>Phospholipids and naturally active phytochemicals that are structurally bound are produced when phosphatidylcholine (or another hydrophilic polar head group) reacts with plant extracts in an aprotic solvent to form phytosomes. The findings of Nazari et&#xa0;al. (<xref ref-type="bibr" rid="B58">58</xref>) indicated that garlic essential oil nanophytosomes have the potential to exhibit desirable physicochemical characteristics, particularly when incorporated into acidic food products (<xref ref-type="bibr" rid="B58">58</xref>). Youssef et&#xa0;al. (<xref ref-type="bibr" rid="B234">234</xref>) also created bio-nano composites from Arabic gum (AG), carboxymethyl cellulose (CMC), titanium dioxide (TiO<sub>2</sub>-NPs), and gelatin (GL) using a solution casting technique, with and without varying volumes of garlic extract. The ability of fresh Nile tilapia fillets to retain their quality in the presence of various pollutants was examined (<xref ref-type="bibr" rid="B234">234</xref>). According to the findings, garlic extract-incorporated CMC/AG/GL/GE&#x2013;TiO<sub>2</sub> bio-nanocomposites demonstrated favorable thermal, mechanical, and morphological characteristics (<xref ref-type="bibr" rid="B234">234</xref>). The application of CMC/AG/GL/GE &#x2013; TiO<sub>2</sub> bio-nanocomposites containing 4% and 8% garlic extract on Nile tilapia fillets inhibited bacterial growth, reduced water loss during cold storage for 21 days (compared to uncoated samples), and extended the shelf life by one week (<xref ref-type="bibr" rid="B234">234</xref>).</p>
<p>By utilizing nano-coating technology, it is possible to extend the freshness of food significantly. To extend the shelf life of various products, antimicrobial and antioxidant properties are generated through the combination of hydrophilic and lipophilic substances, such as plant extracts or other carbohydrates, with metal nanoparticles, including zinc oxide, copper oxide, titanium dioxide, silver, and gold nanoparticles (<xref ref-type="bibr" rid="B235">235</xref>).</p>
</sec>
<sec id="s10" sec-type="conclusions">
<label>10</label>
<title>Conclusions</title>
<p>The potential of garlic in treating various chronic or acute conditions has been the subject of extensive research, as elaborated upon in the current review. The substantial abundance of phytochemicals present enhances many physiological processes. Protein, tryptophan, selenium, manganese, vitamins B1 and B6, and tryptophan are some nutrients found in garlic. The elements above synergize against a diverse range of health-threatening agents. However, further research is required to determine their exact mechanisms of action. Sulfoxide, s-methyl-1-cysteine, linalool, geraniol, and citral are a few of the sulfur-containing compounds found in garlic that have been associated with beneficial effects on health. Thiosulfinates and cysteine sulfoxides are two organic sulfur compounds associated with pharmacological activity. Garlic is increasingly recognized and utilized as fresh garlic juice, oil, garlic extract, and garlic powder, becoming increasingly popular as a natural remedy for various physiological disorders. Due to the unique amalgamation of bioactive constituents in <italic>Allium</italic> vegetables, their incorporation into our daily diet is imperative. Studies conducted <italic>in vitro</italic> and <italic>in vivo</italic> have demonstrated that garlic is beneficial in combating a range of metabolic disorders.</p>
<p>Garlic&#x2019;s hypocholesterolemic, hypoglycemic, anticoagulant, antifungal, antioxidant, and antithrombotic attributes render it a multipurpose sustenance and medicinal substance. It is necessary to isolate and define garlic&#x2019;s relative compounds and conduct additional research into its biological functions. Additional research is necessary to comprehend garlic&#x2019;s mechanisms of action fully. Additional investigation is warranted to ascertain the potential impact of processing techniques such as fermentation and heat on garlic, as such knowledge could compromise the herb&#x2019;s efficacy and safety. Further human clinical trials are required to validate the health benefits of garlic, with an emphasis on assessing its potential safety and adverse effects.</p>
</sec>
<sec id="s11" sec-type="author-contributions">
<title>Author contributions</title>
<p>ME-S: Writing &#x2013; original draft, Formal analysis, Data curation. AS: Writing &#x2013; original draft, Formal analysis, Data curation. SK: Writing &#x2013; original draft, Software. HS: Writing &#x2013; original draft, Resources. TAE-M: Writing &#x2013; original draft, Software, Data curation. SA: Writing &#x2013; original draft, Software, Formal analysis. ME: Writing &#x2013; original draft, Software. SE: Writing &#x2013; original draft, Software, Data curation. WM: Writing &#x2013; original draft, Software, Resources. AAH: Writing &#x2013; original draft, Software, Data curation. BM: Writing &#x2013; original draft, Data curation. NA: Writing &#x2013; original draft, Data curation. AAl: Writing &#x2013; original draft, Software. ME-T: Writing &#x2013; original draft, Software. SAQ: Writing &#x2013; review &amp; editing, Formal analysis. KE-T: Writing &#x2013; review &amp; editing, Investigation. SI: Writing &#x2013; review &amp; editing, Supervision, Resources.</p>
</sec>
</body>
<back>
<sec id="s12" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was funded by the Khalifa Center for Biotechnology and Genetic Engineering-UAEU (Grant number: 12R028) to SAQ. The authors are grateful to the Deanship of Scientific Research at King Khalid University for funding this work through the large group research project under grant number (R.G.P.2/326/45).</p>
</sec>
<ack>
<title>Acknowledgments</title>
<p>This publication was made possible by grant number NC.X-267-5-12-170-1 from the National Institute of Food and Agriculture (NIFA) and the Department of Family and Consumer Sciences and the Agriculture Research Station at North Carolina Agriculture and Technical State University (Greensboro, NC, USA 27411). This work was also supported, in part, by 1890 Capacity Building Program grant no. (2020-38821-31113/project accession no. 021765). The work was also  financially supported by Abu Dhabi Award for Research Excellence-Department of Education and Knowledge (Grant number: 21S105); and UAEU program of Advanced Research (Grant number: 21S169) to KE-T.</p>
</ack>
<sec id="s13" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s14" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
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