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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id>
<journal-title>Frontiers in Pharmacology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Pharmacol.</abbrev-journal-title>
<issn pub-type="epub">1663-9812</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">842511</article-id>
<article-id pub-id-type="doi">10.3389/fphar.2022.842511</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Pharmacology</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>
<italic>Eichhornia crassipes</italic> (Mart.) Solms: A Comprehensive Review of Its Chemical Composition, Traditional Use, and Value-Added Products</article-title>
<alt-title alt-title-type="left-running-head">Ben Bakrim et&#x20;al.</alt-title>
<alt-title alt-title-type="right-running-head">Chemical Products from <italic>Eichhornia crassipes</italic>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Ben Bakrim</surname>
<given-names>Widad</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1458814/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ezzariai</surname>
<given-names>Amine</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1463285/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Karouach</surname>
<given-names>Fadoua</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1436569/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sobeh</surname>
<given-names>Mansour</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/541596/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kibret</surname>
<given-names>Mulugeta</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1458627/overview"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Hafidi</surname>
<given-names>Mohamed</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/651168/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kouisni</surname>
<given-names>Lamfeddal</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/846976/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yasri</surname>
<given-names>Abdelaziz</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1458099/overview"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>African Sustainable Agriculture Research Institute (ASARI)</institution>, <institution>Mohammed VI Polytechnic University (UM6P)</institution>, <addr-line>La&#xe2;youne</addr-line>, <country>Morocco</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>AgroBioSciences Department</institution>, <institution>Mohammed VI Polytechnic University (UM6P)</institution>, <addr-line>Benguerir</addr-line>, <country>Morocco</country>
</aff>
<aff id="aff3">
<label>
<sup>3</sup>
</label>
<institution>Department of Biology</institution>, <institution>Bahir Dar University</institution>, <addr-line>Bahir Dar</addr-line>, <country>Ethiopia</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Laboratoire Biotechnologies Microbiennes</institution>, <institution>Agrosciences et Environnement (BioMagE)</institution>, <institution>Unit&#x00E9; de Recherche Labellis&#x00E9;e CNRST N&#x00B0;4, Faculty of Science Semlalia, Cadi Ayyad University</institution>, <addr-line>Marrakesh</addr-line>, <country>Morocco</country>
</aff>
<aff id="aff5">
<sup>5</sup>
<institution>Institut National de la Recherche Agronomique (INRA)</institution>, <addr-line>Rabat</addr-line>, <country>Morocco</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/898679/overview">Ilkay Erdogan Orhan</ext-link>, Gazi University, Turkey</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1035020/overview">Hazel Monica M. Peralta</ext-link>, Central Luzon State University, Philippines</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/404627/overview">Fardous Mohammad Safiul Azam</ext-link>, Neijiang Normal University, China</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Mohamed Hafidi, <email>hafidi@uca.ac.ma</email>
</corresp>
<fn fn-type="other">
<p>This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>18</day>
<month>03</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>13</volume>
<elocation-id>842511</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>12</month>
<year>2021</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>02</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2022 Ben Bakrim, Ezzariai, Karouach, Sobeh, Kibret, Hafidi, Kouisni and Yasri.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Ben Bakrim, Ezzariai, Karouach, Sobeh, Kibret, Hafidi, Kouisni and Yasri</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&#x20;terms.</p>
</license>
</permissions>
<abstract>
<p>
<italic>Eichhornia crassipes</italic> (Mart.) Solms, commonly known as water hyacinth, is one of the world&#x2019;s most invasive aquatic plants of the Pontederiaceae family occurring in tropical and subtropical regions of the world. Although, <italic>E. crassipes</italic> causes significant ecological and socioeconomic issues such as a high loss in water resources, it has multipurpose applications since it is famous for many industrial applications such as bioenergy, biofertilizer production, wastewater treatment (absorption of heavy metals), and animal feed. Furthermore, <italic>E. crassipes</italic> is rich in diverse bioactive secondary metabolites including sterols, alkaloids, phenolics, flavonoids, tannins, and saponins. These secondary metabolites are well known for a wide array of therapeutic properties. The findings of this review suggest that extracts and some isolated compounds from <italic>E. crassipes</italic> possess some pharmacological activities including anticancer, antioxidant, anti-inflammatory, antimicrobial, skin whitening, neuroprotective, and hepatoprotective activities, among other biological activities such as allelopathic, larvicidal, and insecticidal activities. The present review comprehensively summarizes the chemical composition of <italic>E. crassipes</italic>, reported to date, along with its traditional uses and pharmacological and biological activities.</p>
</abstract>
<kwd-group>
<kwd><italic>Eichhornia crassipes</italic> (mart.) Solms</kwd>
<kwd>phytochemistry</kwd>
<kwd>value&#x2013;added products</kwd>
<kwd>pharmacology</kwd>
<kwd>biological activities</kwd>
</kwd-group>
<contract-sponsor id="cn001">Fondation OCP<named-content content-type="fundref-id">10.13039/501100016150</named-content>
</contract-sponsor>
</article-meta>
</front>
<body>
<sec id="s1">
<title>Introduction</title>
<p>
<italic>Eichhornia crassipes</italic> (Mart.), commonly known as water hyacinth<italic>,</italic> is a monocotyledonous free-floating aquatic plant belonging to the family Pontederiaceae. The plant is native to Brazil and the Amazon, but it has been naturalized in tropical and subtropical regions. It has also been reported in several parts of Africa, including Egypt, Sudan, Kenya, Ethiopia, Nigeria, Zimbabwe, Zambia, and South Africa (<xref ref-type="bibr" rid="B37">Dersseh et&#x20;al., 2019</xref>). The plant is characterized by its high growth, rapid and extensive spread, and strong tolerance to pH and nutrient variations as well as temperature conditions. Hence, it has been recognized by the International Union for Conservation of Nature as one of the 100 most aggressive invasive species and identified as one of the 10 severest weed plants in the world (<xref ref-type="bibr" rid="B124">T&#xe9;llez et&#x20;al., 2008</xref>; <xref ref-type="bibr" rid="B145">Zhang et&#x20;al., 2010</xref>; <xref ref-type="bibr" rid="B93">Patel, 2012</xref>). However, <italic>E. crassipes</italic> possesses many potential benefits but with financial and environmental fallout (<xref ref-type="bibr" rid="B142">Yan et&#x20;al., 2017</xref>; <xref ref-type="bibr" rid="B118">Su et&#x20;al., 2018</xref>). It has been used as phytoremediation agent for wastewater treatments because of its ability to absorb heavy metals and grow in polluted water (<xref ref-type="bibr" rid="B86">Mishra and Maiti, 2017</xref>; <xref ref-type="bibr" rid="B88">Mustafa and Hayder, 2021</xref>). It has also been considered as a potential source of bioenergy (<xref ref-type="bibr" rid="B24">Carre&#xf1;o Sayago and Rodr&#xed;guez, 2018</xref>) and biofertilizers (<xref ref-type="bibr" rid="B84">Manyuchi et&#x20;al., 2019</xref>). Traditionally, the plant is used to treat gastrointestinal disorders, such as diarrhea, intestinal worms, digestive disorders, and flatulence. In addition, the beans were harnessed for healthy spleen functioning (<xref ref-type="bibr" rid="B112">Sharma et&#x20;al., 2020</xref>). The plant is also rich in various bioactive compounds that exhibit a wide array of pharmacological properties.</p>
<p>These include antioxidant (<xref ref-type="bibr" rid="B81">Liu et&#x20;al., 2018</xref>), antimicrobial (<xref ref-type="bibr" rid="B27">Chang and Cheng, 2016</xref>), antitumor (<xref ref-type="bibr" rid="B10">Ali et&#x20;al., 2009</xref>), anticancer (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>), anti-inflammatory (<xref ref-type="bibr" rid="B63">Jayanthi et&#x20;al., 2013</xref>) as well as hepatoprotective (<xref ref-type="bibr" rid="B71">Kumar et&#x20;al., 2014</xref>), larvicidal (<xref ref-type="bibr" rid="B131">Turnipseed et&#x20;al., 2018</xref>), and wound healing (<xref ref-type="bibr" rid="B73">Lalitha and Jayanthi, 2014</xref>). Many patents have also been filed, mainly in the fields of medicinal uses of the plant and its product formulations.</p>
<p>The current review comprehensively assesses the state of the art concerning the phytochemical composition, therapeutic uses, and pharmaceutical applications of <italic>E. crassipes</italic> (Mart.) along with patents reported on the&#x20;plant.</p>
</sec>
<sec id="s2">
<title>Methodology of Research</title>
<p>A literature-based search was conducted to provide an overview of the phytochemistry, value-added products, and pharmacological activities of <italic>E. crassipes</italic>, using accessible online databases such as PubMed, Scopus, Web of Science, and Google Scholar. The literature survey was performed using different keywords including &#x201c;<italic>Eichhornia crassipes&#x201d;</italic> or &#x201c;water hyacinth&#x201d; and chemical constituents, or value-added products, or antioxidant, or anti-inflammatory, or antimicrobial or hepatoprotective or wound healing, which resulted in the gathering of much literature. An extensive number of studies published in research articles, review articles, book chapters, and books were collected. From 2,835 identified studies, a total of 150 studies, which met the inclusion criteria, were preserved in this survey. The outline for literature search and management is presented in <xref ref-type="fig" rid="F1">Figure&#x20;1</xref>.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Flowchart of the selection process of the included studies of <italic>Eichhornia crassipes.</italic>
</p>
</caption>
<graphic xlink:href="fphar-13-842511-g001.tif"/>
</fig>
</sec>
<sec id="s3">
<title>Botanical Description</title>
<p>The Pontederiaceae family possesses nine genera, including <italic>Eichhornia.</italic> The latter is composed of eight species of aquatic plants, among them is <italic>Eichhornia crassipes</italic> (Mart.) Solms: synonym of <italic>Pontederia crassipes</italic> (Mart.). The mature plant has roots, leaves, stolon, inflorescences, and fruit clusters (<xref ref-type="bibr" rid="B92">Parsons and Cuthbertson, 2001</xref>) (<xref ref-type="fig" rid="F2">Figure&#x20;2</xref>). The root morphology is highly plastic and fibrous, having one single main root with many laterals, forming a huge root system. Because each lateral root has a root tip, <italic>E. crassipes</italic> may exploit nutrients in a low-nutrient water body, which makes the lateral roots longer and denser at low phosphorus concentrations.</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>
<bold>(A)</bold> <italic>Eichhornia crassipes</italic> (Mart.) from Lake Tana, Ethiopia. <bold>(B)</bold> Morphology of <italic>E. crassipes</italic>. rt: root; st: stolon; pt: petiole; lb: leaf blade; li: leaf isthmus; dp: daughter plant; in: inflorescence; pf: peduncle of flower&#x20;spike.</p>
</caption>
<graphic xlink:href="fphar-13-842511-g002.tif"/>
</fig>
<p>
<italic>E. crassipes</italic> petioles are both erect and horizontal as stolon. There are two types of leaves, thin and round. The thin ones stand erect while the round ones possess a slightly undulating edge. In addition, the two types of leaves are soft, glossy, and glabrous. The leaves possess semi<bold>-</bold>parallel veins following their curvature (<xref ref-type="bibr" rid="B92">Parsons and Cuthbertson, 2001</xref>). The plant possesses beautiful violet flowers with six petals that may be found throughout the year under favorable conditions. However, the intensity of flowering may differ over the four seasons. The fruit contains 300 seeds in a slim three-celled capsule which measures 1&#x2013;1.5&#xa0;mm long with many longitudinal ribs. In regions with temperatures around 25&#xb0;C, the seeds can remain inactive for up to 20&#xa0;years and then germinate with water. Generally, temperatures between 20 and 35&#xb0;C enhance germination while temperatures around 35&#xb0;C enhance rapid growth (<xref ref-type="bibr" rid="B92">Parsons and Cuthbertson, 2001</xref>; <xref ref-type="bibr" rid="B82">Malik, 2007</xref>).</p>
</sec>
<sec id="s4">
<title>Phytochemistry</title>
<p>The phytochemical composition of <italic>E. crassipes</italic> has been extensively explored, revealing diverse secondary metabolites, among them polyphenols (9.73%), flavonoids (10.49%), fatty acids (10.1%), alkaloids (7.4%), sterols (6.17%), and other compounds (19.13%) as shown in <xref ref-type="fig" rid="F3">Figure&#x20;3</xref>. Several primary metabolites were annotated from the different parts of the plant, which include heteropolysaccharides such as L-galactose, L-arabinose, and D-xylose (<xref ref-type="bibr" rid="B11">Anjaneyalu et&#x20;al., 1983</xref>), as well as hemicellulose, cellulose, glycolipids, and triacylglycerols (<xref ref-type="bibr" rid="B16">Balasubramanian et&#x20;al., 2012</xref>). Phosphatidylethanolamine, phosphatidylcholine, and phosphatidylglycerol are the main phospholipids identified in the flowers, leaves, stalks, and roots (<xref ref-type="bibr" rid="B74">Lalitha and Jayanthi, 2012</xref>). The leaves contain several amino acids and are mainly rich in leucine, asparagine, and glutamine (<xref ref-type="bibr" rid="B135">Virabalin et&#x20;al., 1993</xref>). Two fractions of peptides have also been identified from the leaves as Leu-Phe and Phe-Phe-Glu (<xref ref-type="bibr" rid="B144">Zhang et&#x20;al., 2018</xref>).</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Major classes and subclasses of compounds isolated from <italic>E. crassipes</italic> based on the total number of phytochemicals. The keywords used on the Web of Science were &#x201c;<italic>E</italic>. <italic>crassipes</italic>,&#x201d; OR &#x201c;water hyacinth&#x201d; &#x201c;phytocompounds,&#x201d; &#x201c;secondary metabolites,&#x201d; &#x201c;phenolic,&#x201d; &#x201c;flavonoids,&#x201d; &#x201c;saponins,&#x201d; &#x201c;sterols,&#x201d; &#x201c;terpenoids,&#x201d; &#x201c;carbohydrates,&#x201d; &#x201c;quinones,&#x201d; &#x201c;tannins,&#x201d; &#x201c;organic acids,&#x201d; and &#x201c;other compounds.&#x201d;</p>
</caption>
<graphic xlink:href="fphar-13-842511-g003.tif"/>
</fig>
<sec id="s4-1">
<title>Phenolic Compounds</title>
<p>Many studies have identified and quantified phenolic compounds in <italic>E. crassipes</italic> (<xref ref-type="bibr" rid="B121">Surendraraj et&#x20;al., 2013</xref>; <xref ref-type="bibr" rid="B132">Tyagi and Agarwal, 2017b</xref>). Simple phenols were identified in different extracts from different parts of <italic>E. crassipes</italic> collected from India. They are represented by pyrogallol (1), 4-methylresorcinol (2), catechol (3), 2-methylresorcinol (4), and resorcinol (5). Moreover, many phenolic acids were detected in different types of extracts of the leaves, petioles, and flowers of <italic>E. crassipes</italic>. They are represented by <italic>p</italic>-hydroxybenzoic (6), gentisic (7), chlorogenic (8), caffeic (9), <italic>p</italic>-coumaric (10), ferulic (11), vanillic (12), syringic (13), gallic (14), protocatechuic (15), and salicylic acids (16) (<xref ref-type="bibr" rid="B75">Lata and Dubey, 2010</xref>; <xref ref-type="bibr" rid="B121">Surendraraj et&#x20;al., 2013</xref>). The ethanolic extract of flowers contained higher levels of gentisic, protocatechuic acids, and p-hydroxybenzoic acid than that of the petioles and leaves (<xref ref-type="bibr" rid="B121">Surendraraj et&#x20;al., 2013</xref>). The chemical structures of phenolic compounds are illustrated in <xref ref-type="sec" rid="s14">Supplementary Figure&#x20;S1</xref>.</p>
</sec>
<sec id="s4-2">
<title>Flavonoids</title>
<p>
<italic>E. crassipes</italic> extracts are rich in flavonoids and their glycosides (<xref ref-type="bibr" rid="B75">Lata and Dubey, 2010</xref>; <xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>). The aqueous and petroleum extracts of the rhizome and shoot were characterized by the presence of gossypetin (17), tricin (18), azaleatin (19) chrysoeriol (20), luteolin (21), and apigenin (22). In addition, orientin (23), kaempferol (24), quercetin (25), and isovitexin (26) were also identified from the roots and shoots (<xref ref-type="bibr" rid="B91">Nyananyo et&#x20;al., 2007</xref>; <xref ref-type="bibr" rid="B76">Lata and Veenapani, 2010</xref>; <xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>). Naringenin (27), kaempferol (24), myricetin (28), and rutin (29) were reported in the leaves and petiole (<xref ref-type="bibr" rid="B29">Chantiratikul et&#x20;al., 2009</xref>). Quercetin 7-methyl ether (30) was recently isolated from the ethanol extract of the plant (<xref ref-type="bibr" rid="B41">Elvira et&#x20;al., 2018</xref>). An acylated delphinidin glycoside represented by 6&#x2034;-<italic>O</italic>-{delphinidin 3-<italic>O</italic>-[6&#x2034;-<italic>O</italic>-(&#x3b2;-d-glucopyranosyl)]} {6&#x2034;-<italic>O</italic>-[apigenin 7-<italic>O</italic>-(&#x3b2;-d-glucopyranosyl)]} malonate (31) was isolated from the flowers and was not detected in any other parts of the plant (<xref ref-type="bibr" rid="B129">Toki et&#x20;al., 1994</xref>) (<xref ref-type="sec" rid="s14">Supplementary Figure S2</xref>). Anthocyanins, a subgroup of flavonoids, have been detected in the ethanol, acetone, and aqueous extracts of the shoots and leaves parts of <italic>E. crassipes</italic> collected from India (<xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>).</p>
</sec>
<sec id="s4-3">
<title>Saponins</title>
<p>Many studies have confirmed the presence of saponins in various extracts of different parts of <italic>E. crassipes</italic> (<xref ref-type="bibr" rid="B18">Baral and Vaidya, 2011</xref>; <xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>; <xref ref-type="bibr" rid="B52">Hamid et&#x20;al., 2013</xref>; <xref ref-type="bibr" rid="B45">Anusiya et&#x20;al., 2020</xref>). Saponins were detected in the aqueous extracts from samples collected from the Phewa Lake in Nepal (<xref ref-type="bibr" rid="B19">Baral and Vaidya, 2011</xref>). By contrast, aqueous extracts of the plant from Dijla River, Baghdad, showed the absence of saponins (<xref ref-type="bibr" rid="B52">Hamid et&#x20;al., 2013</xref>). Moreover, the phytochemical screening of hexane, chloroform, and ethanol extracts revealed the presence of saponins from samples collected from Nepal (<xref ref-type="bibr" rid="B19">Baral and Vaidya, 2011</xref>; <xref ref-type="bibr" rid="B17">Baral et&#x20;al., 2012</xref>; <xref ref-type="bibr" rid="B74">Lalitha and Jayanthi, 2012</xref>). For instance, two steroidal saponins, namely spirostane (32) and cholestane (33) were isolated from <italic>E. crassipes</italic>. The first was found in the acetone extract of the roots and the second in the cyclohexane leaf extract of <italic>E. crassipes</italic> (<xref ref-type="bibr" rid="B43">Fileto-P&#xe9;rez et&#x20;al., 2015</xref>) as shown in <xref ref-type="sec" rid="s14">Supplementary Figure S3</xref>. These compounds characterized the plant collected from India and were not detected elsewhere.</p>
</sec>
<sec id="s4-4">
<title>Terpenoids</title>
<p>Phytol (34) was identified by GC-MS in the ethanol extract from the whole plant collected from India (<xref ref-type="bibr" rid="B89">Muthunarayanan et&#x20;al., 2011</xref>; <xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>). This compound is considered a major bioactive compound present in the leaves of the plants collected from India (<xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>; <xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>). Squalene (35), a hypocholesterolemic terpenoid, was identified in the non-polar and polar extracts of the leaves and stems of <italic>E. crassipes</italic>, from Mexico (<xref ref-type="sec" rid="s14">Supplementary Figure S4</xref>) (<xref ref-type="bibr" rid="B43">Fileto-P&#xe9;rez et&#x20;al., 2015</xref>). This compound has been only identified in the Mexican plant. GC-MS studies conducted by <xref ref-type="bibr" rid="B79">Lenora et&#x20;al. (2016)</xref> have reported the presence camarolide (36), a pentacyclic triterpenoid, in the methanol extract of the aerial parts of the&#x20;plant.</p>
</sec>
<sec id="s4-5">
<title>Fatty Acids</title>
<p>The GC-MS analysis of the leaves of <italic>E. crassipes</italic> revealed the presence of many fatty acids represented by linolenic acid, ethyl ester (37) (26.26%), palmitic acid ethyl ester (38) (12.09%), &#x3b1;-glyceryl linolenate (39) (1.35%), E-11-hexadecenoic acid, ethyl ester (40) (1.04%), and stearic acid, ethyl ester (41) (0.98%). The GC-MS of the petiole part revealed the presence of hexadecanoic acid, ethyl ester, synonym of palmitic acid, ethyl ester (37) (23.7%), 9,12,15-octadecatrienoic acid, ethyl ester, (Z,Z,Z) (42) (5.50%), and n-hexadecanoic acid (43) (3.82%) (<xref ref-type="bibr" rid="B132">Tyagi and Agarwal, 2017b</xref>). The latter was also identified in the shoot extracts (<xref ref-type="bibr" rid="B45">Anusiya et&#x20;al., 2020</xref>). Other fatty acids were identified in different types of extracts from the leaves, stems, and roots. These include linolenic acid (44), caprylic acid (45), lauric acid (46), myristic acid (47), oleic acid (48), vaccenic acid (49), tetracosanoic acid (50), and 10,12-octadecadienoic acid (51), and cis-vaccenic acid (52) (<xref ref-type="bibr" rid="B43">Fileto-P&#xe9;rez et&#x20;al., 2015</xref>; <xref ref-type="bibr" rid="B6">Adelodun et&#x20;al., 2020</xref>) (<xref ref-type="sec" rid="s14">Supplementary Figure&#x20;S5</xref>).</p>
</sec>
<sec id="s4-6">
<title>Sterols</title>
<p>Phytosterols are steroidal molecules with a similar structure to cholesterol found in many vegetables (<xref ref-type="bibr" rid="B139">Wasowicz and Rudzinska, 2011</xref>). Sterols represent 19&#x2013;23% wt<italic>.</italic> of the extracts of <italic>E. crassipes</italic>. 6&#x3b1;-Hydroxystigmata-4,22-dien-3-one (53), 4&#x3b1;-methyl-5&#x3b1;-ergosta-7,24(28)-diene-3&#x3b2;,4&#x3b2;-diol (54), 4&#x3b1;-methy1-5&#x3b1;-ergosta-8,14,24(28)-triene-3&#x3b2;,4&#x3b2;-diol (55), and 4&#x3b1;-methyl-5&#x3b1;-ergosta-8-24(28)-triene-3&#x3b2;,4&#x3b2;-diol (56) were isolated from the ethyl acetate extract of the plant (<xref ref-type="bibr" rid="B33">DellaGreca et&#x20;al., 1991</xref>). &#x3b2;-campesterol (57), methylcholesterol (58), &#x3b2;-sitosterol (59), and sitosterol (60) were detected in the stalk and leaf extracts. The stalk parts showed the maximum content of stigmasterol (61) (<xref ref-type="bibr" rid="B47">Goswami et&#x20;al., 1983</xref>; <xref ref-type="bibr" rid="B114">Silva et&#x20;al., 2015</xref>; <xref ref-type="bibr" rid="B116">Singh et&#x20;al., 2015</xref>; <xref ref-type="bibr" rid="B85">Martins et&#x20;al., 2016</xref>; <xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>). Stigmasterol is considered the most common and major phytosterol identified in different parts of <italic>E. crassipes</italic> (<xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>; <xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>). Furthermore, &#x3b2;-stigmasterol (62) was found in hexane, acetone, and methanolic extracts of the leaves and stems (<xref ref-type="bibr" rid="B43">Fileto-P&#xe9;rez et&#x20;al., 2015</xref>).</p>
<p>Recently, a novel derivative of stigmasterol named 22,23-dibromostigmasterol acetate (63) was isolated from the ethanolic extract of the shoots and amounted to 28.72% of the extract (<xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>; <xref ref-type="bibr" rid="B45">Anusiya et&#x20;al., 2020</xref>). The structures of these chemicals are represented in the supplementary materials in <xref ref-type="sec" rid="s14">Supplementary Figure&#x20;S6</xref>.</p>
</sec>
<sec id="s4-7">
<title>Alkaloids</title>
<p>
<italic>E. crassipes</italic> is considered a potential source of alkaloids. They represent 0.98% of the crude extract of the plant (<xref ref-type="bibr" rid="B107">Shanab et&#x20;al., 2010</xref>). In the rhizome and shoot, tomatine (64) and cytisine (65) were found to predominate. Quinine (66), thebaine (67), and codeine (68) exist only in the shoot while nicotine (69) is found mainly in the rhizome of the Indian species (<xref ref-type="bibr" rid="B75">Lata and Dubey, 2010</xref>). In addition, 1H-pyrrole,1-phenyl (70) and pipradrol (71) were identified in the ethanol extract using GC-MS (<xref ref-type="bibr" rid="B107">Shanab et&#x20;al., 2010</xref>; <xref ref-type="bibr" rid="B108">Shanab et&#x20;al., 2011</xref>). Furthermore, 18,19-secoyohimban-19-oic acid-16,17,20,21-tetradehydro-16-(hydroxymethyl)-methyl ester (72), di amino-di-nitro-methyl dioctyl phthalate (73), and 9-(2&#x2032;,2&#x2032;-dimethyl-propanoilhydrazono)-2,7-bis-[2-(diethylamino)-ethoxy]fluorene (74) were isolated from leaf extracts (<xref ref-type="sec" rid="s14">Supplementary Figure S7</xref>) (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>; <xref ref-type="bibr" rid="B87">Mtewa et&#x20;al., 2018</xref>).</p>
</sec>
<sec id="s4-8">
<title>Quinones and Anthraquinones</title>
<p>The shoot extracts were reported to contain several quinones represented by aloe-emodin (75), 7-methyl-juglone (76), and rhein (77), whereas aloe-emodin (75) was found in the rhizome as well (<xref ref-type="bibr" rid="B76">Lata and Veenapani, 2010</xref>). Anthraquinones, on the other hand, were found in all extracts except the light petroleum fraction (<xref ref-type="sec" rid="s14">Supplementary Figure S8</xref>) (<xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>; <xref ref-type="bibr" rid="B130">Tulika and Mala, 2015</xref>; <xref ref-type="bibr" rid="B45">Anusiya et&#x20;al., 2020</xref>).</p>
</sec>
<sec id="s4-9">
<title>Phenalene and Phenylphenalene Derivatives</title>
<p>Permethylated phenalene derivatives were identified from <italic>E. crassipes</italic> represented by 2,6-dimethoxy-9-phenylphenalenone (78), 4,5-dimethoxy-9-phenyl-2,3-dihydrophenalen-1-ol-<italic>O</italic>-methyl ether (79), 4,9-dimethoxy-7-(4&#x2032;-methoxy-phenyl)-2,3-dihydro-phenalen-1-ol-<italic>O</italic>-methyl ether (80), and 4,9-dimethoxy-7-phenyl-2,3-dihydrophenalen-1-ol-<italic>O</italic>-methyl ether (81) (<xref ref-type="bibr" rid="B32">DellaGreca et&#x20;al., 1992</xref>). In addition, 8-phenylphenalenone compounds represented by 2-hydroxy-8-(4-hydroxyphenyl)-phenalen-1-one (82) and 2- hydroxy-8-(3,4-dihydroxyphenyl)-phenalen-1-one (83) were obtained from the acetone extract of the roots and leaves of the plant (H&#xf6;lscher and Schneider, 2005).</p>
<p>Phenylphenalene derivatives were also identified and isolated. They were represented by 4,8,9-trimethoxy-1-phenyl-2,3-dihydro-1H-phenalene (84), 4,8,9-trimethoxy-1-(4 methoxyphenyl)-2,3-dihydro-1H-phenalene (85), 4,4&#x2033;,8,8&#x2033;,9,9&#x2033;-hexamethoxy-1,1&#x2033;-diphenyl-2,2&#x2033;,3,3&#x2033;-tetrahydro-7,7&#x2033;-bi(1H-phenalene) (86), 4,4&#x2033;,8,8&#x2033;,9,9&#x2033;,4&#x2032;,4&#x2034;-octamethoxy-1,1&#x2033;-diphenyl-2,2&#x2033;,3,3&#x2033;-tetrahydro-7,7&#x2033;-bi(1<italic>H</italic>-phenalene) (87), 6,6&#x2033;,8,8&#x2033;,9,9&#x2033;,4&#x2032;,4&#x2034;-octamethoxy-1,1&#x2033;-diphenyl-2,2&#x2033;,3,3&#x2033;-tetrahydro-7,7&#x2033;-bi(1<italic>H</italic>-phenalene) (88), methyl 5-methoxy-2-phenyl-8[3,7,10-trimethoxy-6-phenyl-5,6-dihydro-4H-phenaleno(2,1-b)furan-9-yl]-1-naphthoate (89), 2,3-dihydro-4,8-dimethoxy-9-phenyl-1H-phenalen-1-ol (90), 2,3-dihydro-8-methoxy-9-phenyl-1H-phenalene-1,4-diol (91), 2,3-dihydro-9-(4-hydroxyphenyl)-8-methoxy-1H-phenalene-1,4-diol (92), together with 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one (93), 2-hydroxy-9-(4-hydroxyphenyl)-1H-phenalen-1-one (94), and 2,3-dihydro-3,9-dihydroxy-5-methoxy-4-phenyl-1H-phenalen-1-one (95). Moreover, 5,6-dimethoxy-7-phenyl-1H-phenalen-1-one (96), 2-hydroxy-9-(4-hydroxyphenyl)-1H-phenalen-1-one (97), and methyl 3-(4-hydroxy 3-methoxyphenyl)prop-2-enoate) (98) were isolated from the ethyl acetate fraction of the whole plant (<xref ref-type="bibr" rid="B34">DellaGreca et&#x20;al., 2008</xref>; <xref ref-type="bibr" rid="B35">DellaGreca et&#x20;al., 2009</xref>; <xref ref-type="bibr" rid="B138">Wang et&#x20;al., 2017</xref>). The later compounds were identified in the plant collected from Naples. Structures are represented in <xref ref-type="sec" rid="s14">Supplementary Figure&#x20;S9</xref>.</p>
</sec>
<sec id="s4-10">
<title>Carbohydrates</title>
<p>Sucrose (99), fructose (100), glucose (101), xylose (102), arabinose (103), and galactose (104) are the main soluble sugars present in the leaves, along with galactomannan (105) and branched (1&#x2192;3)-&#x3b2;-D-glucan (<xref ref-type="bibr" rid="B148">Arifkhodzhaev and Shoyakubov, 1995</xref>). The chloroform and aqueous extracts of the shoots revealed the presence of cardiac glycosides, however, they were absent in the rhizome (<xref ref-type="bibr" rid="B75">Lata and Dubey, 2010</xref>). Sulfated polysaccharides were found in the whole plant<italic>,</italic> with high amounts in the roots (<xref ref-type="bibr" rid="B31">Dantas-Santos et&#x20;al., 2012</xref>). Furthermore, cellulose xanthate was produced from the chemical treatment of <italic>E. crassipes</italic> shoot and root biomass with NaOH and CS<sub>2</sub> (<xref ref-type="bibr" rid="B147">Zhou et&#x20;al., 2009</xref>), which is known for its ability to adsorb heavy metals (<xref ref-type="bibr" rid="B36">Deng et&#x20;al., 2012</xref>). Nanocrystalline cellulose was isolated from <italic>E. crassipes</italic> fibers after chemical and mechanical treatments (<xref ref-type="bibr" rid="B15">Asrofi et&#x20;al., 2017</xref>). Xylitol (106), a pentose polyol, used in food and pharmaceutical industries, was also isolated and identified from the plant (<xref ref-type="bibr" rid="B96">Prakasham et&#x20;al., 2009</xref>). Different studies reported the yield of xylose from <italic>E. crassipes</italic> biomass. <xref ref-type="bibr" rid="B66">Kalhorinia et&#x20;al. (2014)</xref> reported a yield of 35&#xa0;g/L of xylitol using simple and efficient acid pretreatment, while 0.25&#xa0;g/L of xylitol was produced from the hemicellulosic parts of the plant by acid hydrolysis (<xref ref-type="bibr" rid="B110">Shankar et&#x20;al., 2020</xref>). The worldwide market of xylitol is more than 700 million USD/year in the food and pharmaceutical industries and is expected to reach 1.37 USD billion by 2025. The selling price of xylitol is estimated to be 5&#xa0;USD/kg (<xref ref-type="sec" rid="s14">Supplementary Figure S10</xref>) (<xref ref-type="bibr" rid="B100">Raj and Krishnan, 2020</xref>).</p>
</sec>
<sec id="s4-11">
<title>Organic Acids</title>
<p>In total, 20 organic acids were identified in different types of extracts from the leaves, stem, and roots of the Mexican plant. These include oxalic acid (107), nonanoic acid (108), malonic acid (109), succinic acid (110), and phthalic acid (111) (<xref ref-type="bibr" rid="B43">Fileto-P&#xe9;rez et&#x20;al., 2015</xref>). While, propiolic acid (112) was identified from the ethanolic extract of the leaves as a major compound from the plant collected from India (<xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>).</p>
<p>Furthermore, levulinic acid (113) extracted with microwave heating techniques was isolated from the dried plant with a yield of 9.43% dry weight (<xref ref-type="bibr" rid="B72">Lai et&#x20;al., 2011</xref>). From the aerial parts, shikimic acid (114), an antiviral agent, was isolated with a yield of 0.03&#x2013;3.25% <italic>w/w</italic> from 1.0&#xa0;g of plant material (<xref ref-type="bibr" rid="B21">Bochkov et&#x20;al., 2012</xref>; <xref ref-type="bibr" rid="B23">Cardoso et&#x20;al., 2014</xref>; <xref ref-type="bibr" rid="B79">Lenora et&#x20;al., 2016</xref>). Isoascorbic acid (115), ascorbic acid (116), and dehydroascorbic acid (117) were present in the shoot extracts, however, the latter was detected only in the rhizome (<xref ref-type="bibr" rid="B75">Lata and Dubey. 2010</xref>). Humic acids, which play an essential role in retaining water and texture soils were also found to be present in several parts of the plant such as the leaves, stems, and roots (<xref ref-type="sec" rid="s14">Supplementary Figure S11</xref>) (<xref ref-type="bibr" rid="B46">Ghabbour et&#x20;al., 2004</xref>).</p>
</sec>
<sec id="s4-12">
<title>Other Compounds</title>
<p>Other metabolites belonging to different classes were detected in different parts of <italic>E. crassipes</italic>.</p>
<p>Phenylnaphthalenedicarboxylic acids were isolated from the acid fraction of the ethyl acetate extract of <italic>E. crassipes</italic> and identified as 2-(<italic>p</italic>-methoxyphenyl)-5-methoxy-1,8-naphthalenedicarboxylic acid dimethyl ester (118), 2-phenyl-6-methoxy-1,8-naphthalenedicarboxylic acid dimethyl ester (119), 2-phenyl-1,8-naphthalenedicarboxylic acid dimethyl ester linked at C-5 to a phenalenol (120) and 2-phenyl-5-methoxy-1,8-naphthalenedicarboxylic acid dimethyl ester (121) (<xref ref-type="bibr" rid="B149">Greca et&#x20;al., 1993</xref>).</p>
<p>4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl (122) was obtained from the ethanol extract of the leaves (<xref ref-type="bibr" rid="B89">Muthunarayanan et&#x20;al., 2011</xref>).</p>
<p>Glycerol-1,9-12(ZZ)-octadecadienoic ester (123) and N-phenyl-2-naphthylamine (124) were isolated from the acetone extract of the roots (<xref ref-type="bibr" rid="B111">Shanyuan et&#x20;al., 1992</xref>).</p>
<p>2,2-dimethylcyclopentanone (125), isocyanoethyl acetate (126), and propane amide (127) were separated from the acetone extract and demonstrated anti-algal activity (<xref ref-type="bibr" rid="B64">Jin et&#x20;al., 2003</xref>). The plant collected from Mexico contained high levels of melatonin (128) and N<sup>1</sup>-acetyl-N<sup>2</sup>-formyl-5- methoxykynuramine (129), two strong free radical scavengers (<xref ref-type="bibr" rid="B122">Tan et&#x20;al., 2007</xref>).</p>
<p>Moreover, 1,2-benzenedicarboxylic acid, mono-(2-ethylhexyl) ester (130), 1,2-benzenedicarboxylic acid, dioctyl ester (131), 1,2-benzenedicarboxylic acid, diisooctyl ester (132), (3-methylphenyl)-phenylmethanol (133), and 4-(diethylamino)-alpha-[4-(diethylamino) phenyl] (134) have been identified from <italic>E. crassipes</italic> extracts collected from River Nile, Egypt (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>). It is noteworthy to say that these compounds were only identified in the plant from Egypt. The GC-MS analysis of the oily fraction, extracted with n-hexane from the whole plant of <italic>E. crassipes</italic>, resulted in the identification of 18 compounds. The most abundant compounds were long-chain alcohols in addition to long-chain nitrogenous compounds like nonadecan-4-ol (135), 17-methoxydocosa-1,4,7,10-tetraene-6,9-dione (136), 9,16-dimethylnonadec-1-en-9-ol (137), tricosane-4-ol (138), 5-methoxy heneicosane (139), 1-aminooctadeca-8,10,12-trien-7-ol (140), and 6-(6-(octadeca-1,3,7,12,14,16-hexaenyl)pyridin-2-yl)hex-5-en-1-ol (141) (<xref ref-type="bibr" rid="B57">Hussain et&#x20;al., 2015</xref>). GC-MS studies conducted by <xref ref-type="bibr" rid="B79">Lenora et&#x20;al. (2016)</xref> have reported the presence of some chemicals in the methanol extract of the aerial parts of the plant. These include 1,8 dipropoxyanthraquinone (142), erucylamide (143), nonacosane (144), and docosane (145). GC-MS analysis of the ethanolic leaf extract led to the identification of various phytochemical compounds including 17-pentatriacontene (146) and octasiloxane (147) considered as major compounds (<xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>). GC-MS analysis of the ethanolic leaves extract led to the identification of 1-monolinoleoylglycerol trimethylsilyl ether (148) (<xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>,; <xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>). The compound was also identified and amounted to 30.89% of the ethanolic extracts of the roots (<xref ref-type="bibr" rid="B69">Kumar et&#x20;al., 2018a</xref>).</p>
<p>Moreover, 14-heptadecenal (149), 16-heptadecenal (150), 4-methyl (phenyl)silyloxypentadecane (151), 3,6-methano-8H-1,5,7-trioxacyclopenta[1J]cyclopro [A]azulene-4,8(3H), 1,4-dioxane-2,5-dione, 3,6-dimethyl (152), 1-hexyl-2-nitrocyclohexane (153), and nonanoic acid, 5-methyl-, ethyl ester (154) were isolated from the ethanolic extract of the shoot and root parts of the plant collected from India (<xref ref-type="sec" rid="s14">Supplementary Figure S12</xref>) (<xref ref-type="bibr" rid="B45">Anusiya et&#x20;al., 2020</xref>).</p>
</sec>
</sec>
<sec id="s5">
<title>Value-Added Products From <italic>E. crassipes</italic> (Mart.) Solms</title>
<p>The biorefinery of <italic>E. crassipes</italic> biomass revealed several enzymes and valuable products. Furfural and hydroxymethylfurfural, for instance, were produced using the nonhazardous oxidant (FeCl<sub>3</sub>) method with the highest yield of 7.9&#xa0;<italic>wt</italic>% of the dry mass of the plant (<xref ref-type="bibr" rid="B81">Liu et&#x20;al., 2018</xref>; <xref ref-type="bibr" rid="B94">Poomsawat et&#x20;al., 2019</xref>). Moreover, due to <italic>E. crassipes</italic> availability, low price, and its high percentage of cellulose, the plant is considered a favorable source to produce fibers, superconductors, and supercapacitors (<xref ref-type="bibr" rid="B127">Sundari and Ramesh, 2012</xref>; <xref ref-type="bibr" rid="B15">Asrofi et&#x20;al., 2017</xref>; <xref ref-type="bibr" rid="B115">Sindhu et&#x20;al., 2017</xref>). The liquid tar obtained from the plant (rich in phenolic compounds) yielded 29% of carbon fiber, which makes the plant suitable for fiber production (<xref ref-type="bibr" rid="B117">Soenjaya et&#x20;al., 2015</xref>).</p>
<p>In addition, different biopolymers with diverse applications along with several enzymes such as cellulase, &#x3b2;-glucosidase, and xylanase were obtained from the plant biomass (<xref ref-type="table" rid="T1">Table&#x20;1</xref>). The enzymes are produced from the plant residue, as carbon source, by submerged fermentation or under solid state fermentation using different microorganisms. The production of these enzymes harnessed on large for cost-effective industrial applications. <xref ref-type="table" rid="T2">Table&#x20;2</xref> presents the different enzymes produced from <italic>E. crassipes</italic> residue.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Value-chemicals produced from <italic>E. crassipes</italic> and their applications.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Products</th>
<th align="center">Process</th>
<th align="center">Yield</th>
<th align="center">Applications</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="2" align="left">Furfurals and hydroxymethylfurfural</td>
<td align="left">Chemical and thermal pretreatment on lignocellulosic biomass</td>
<td rowspan="2" align="center">7.9%/DM</td>
<td rowspan="2" align="left">Biorefinery product fossil oil derivatives</td>
<td align="left">
<xref ref-type="bibr" rid="B94">Poomsawat et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td align="left">Nonhazardous oxidant (FeCl<sub>3</sub>)</td>
<td align="left">
<xref ref-type="bibr" rid="B81">Liu et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Cellulose xanthogenate</td>
<td rowspan="2" align="left">Extraction with NaOH and CS<sub>2</sub> yielded alkali-treatement</td>
<td rowspan="2" align="center">DN</td>
<td rowspan="2" align="left">Increase the heavy metal adsorption</td>
<td align="left">
<xref ref-type="bibr" rid="B147">Zhou et&#x20;al. (2009)</xref>
</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B36">Deng et&#x20;al. (2012)</xref>
</td>
</tr>
<tr>
<td align="left">Hydrogel</td>
<td align="left">Chemical treatments</td>
<td align="center">DN</td>
<td align="left">Potential for future applications in nanocomposites</td>
<td align="left">
<xref ref-type="bibr" rid="B127">Sundari and Ramesh, (2012)</xref>
</td>
</tr>
<tr>
<td align="left">Polyhydroxyalkanoate</td>
<td align="left">Acid pretreatment &#x2b; fermentation by <italic>Pseudomonas aeruginosa</italic>
</td>
<td align="center">65.51%/DM</td>
<td align="left">Biopolymer: bioplastic</td>
<td align="left">
<xref ref-type="bibr" rid="B151">Preethi and Vineetha (2015)</xref>
</td>
</tr>
<tr>
<td align="left">Hydrogel</td>
<td align="left">Polyvinyl alcohol &#x2b; glutaraldehyde</td>
<td align="center">DN</td>
<td align="left">Biopolymer (control release technology)</td>
<td align="left">
<xref ref-type="bibr" rid="B152">Setyaningsih et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td align="left">Polyhydroxybutyrate</td>
<td align="left">Alkaline, peracetic acid pretreatment and enzymatic saccharification (by <italic>Ralstonia eutropha</italic> ATCC 17699)</td>
<td align="center">73%/DM</td>
<td align="left">Biopolymer: the most important biodegradable plastics</td>
<td align="left">
<xref ref-type="bibr" rid="B150">Saratale et&#x20;al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Nanofibers</td>
<td align="left">Chemical and mechanical treatments</td>
<td align="center">DN</td>
<td align="left">Composites, biodegradable thin films, adsorbents</td>
<td align="left">
<xref ref-type="bibr" rid="B127">Sundari and Ramesh, (2012)</xref>
</td>
</tr>
<tr>
<td align="left">Carbon fiber</td>
<td align="left">Water hyacinth liquid tar</td>
<td align="center">29%/DM</td>
<td align="left">Precursor for the preparation of composite materials</td>
<td align="left">
<xref ref-type="bibr" rid="B117">Soenjaya et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td align="left">Carbon microsphere</td>
<td align="left">Subcritical water process</td>
<td align="center">0.1019&#xa0;g/g&#x20;DM</td>
<td align="left">-</td>
<td align="left">
<xref ref-type="bibr" rid="B153">Kurniawan et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td align="left">Composite</td>
<td align="left">Solution impregnation and hot curving methods</td>
<td align="center">DN</td>
<td align="left">Natural fibers are reinforced with polymer composites to produce low-cost materials of engineering</td>
<td align="left">
<xref ref-type="bibr" rid="B44">Ramirez et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td align="left">Nanocrystalline cellulose</td>
<td align="left">Chemical and mechanical treatments</td>
<td align="center">DN</td>
<td align="left">Potential application in various fields, especially as a reinforcing agent in bionanocomposites</td>
<td align="left">
<xref ref-type="bibr" rid="B15">Asrofi et&#x20;al. (2017)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Laccase</td>
<td align="left">Solid state fermentation by <italic>Pycnoporus sanguineus</italic> SYBC-L1</td>
<td align="center">32.02 U/DM</td>
<td rowspan="2" align="left">Application in harsh industry</td>
<td align="left">
<xref ref-type="bibr" rid="B138">Wang et&#x20;al. (2017)</xref>
</td>
</tr>
<tr>
<td align="left">Synthesis by <italic>Phanerochaete chrysosporium</italic> NCIM 1197</td>
<td align="center">16.74 U/DM</td>
<td align="left"/>
</tr>
<tr>
<td align="left">Biopolymer composites</td>
<td align="left">Extraction of water hyacinth fibers &#x2b; tapioca powder</td>
<td align="center">10%/DM</td>
<td align="left">Mechanical and thermal properties. Thermal resistance and the lowest moisture absorption</td>
<td align="left">
<xref ref-type="bibr" rid="B5">Abral et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td align="left">Water hyacinth composite/NiO composite</td>
<td align="left">Carbonization of water hyacinth &#x2b; hydrothermal route</td>
<td align="center">DN</td>
<td align="left">Electrode materials for supercapacitors</td>
<td align="left">
<xref ref-type="bibr" rid="B97">Qiu et&#x20;al. (2017)</xref>
</td>
</tr>
<tr>
<td align="left">Bionanocomposite</td>
<td align="left">Ultrasonic vibration during gelation</td>
<td align="center">DN</td>
<td align="left">Bioplastic</td>
<td align="left">
<xref ref-type="bibr" rid="B14">Asrofi et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td align="left">Supercapacitor electrodes</td>
<td align="left">Energy-saving hydrothermal carbonization</td>
<td align="center">DN</td>
<td align="left">Functional carbon materials</td>
<td align="left">
<xref ref-type="bibr" rid="B106">Saning et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td align="left">Polymer nanocomposite</td>
<td align="left">Acrylic acid &#x2b; nano-hydroxyapatite (nano-HA)</td>
<td align="center">DN</td>
<td align="left">Potential agricultural application</td>
<td align="left">
<xref ref-type="bibr" rid="B98">Kiplangat et&#x20;al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Iron oxide nanoparticles (FeNPs)</td>
<td align="left">Green chemistry approach</td>
<td align="center">77.08%/DM</td>
<td align="left">Different applications in different fields such as cosmetic, paints, agriculture, food, coatings, healthcare, and material science</td>
<td align="left">
<xref ref-type="bibr" rid="B60">Jagathesan and Rajiv (2018)</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>DN, data not available; DM , dry&#x20;mass.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>Enzymes produced from <italic>E. crassipes</italic> residue.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Enzymes</th>
<th align="center">Applications</th>
<th align="center">Microorganisms</th>
<th align="center">Process</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="6" align="left">Cellulase</td>
<td rowspan="6" align="left">Food, textiles, and paper industry</td>
<td rowspan="2" align="left">
<italic>Trichoderma reesei</italic>
</td>
<td rowspan="2" align="left">Fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B38">Deshpande et&#x20;al. (2009)</xref>
</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B146">Zhao et&#x20;al. (2011)</xref>
</td>
</tr>
<tr>
<td/>
<td/>
<td align="left">
<xref ref-type="bibr" rid="B83">Manivannan and Narendhirakannan (2014)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>Aspergillus niger</italic>
</td>
<td align="left">Submerged fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B95">Pothiraj et&#x20;al. (2016)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>Trichoderma viride</italic>
</td>
<td/>
<td/>
</tr>
<tr>
<td align="left">
<italic>Aspergillus niger</italic>
</td>
<td align="left">Physical and biophysical pretreatment &#x2b; fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B154">Amriani et&#x20;al. (2016)</xref>
</td>
</tr>
<tr>
<td align="left">&#x3b2;-glucosidase</td>
<td align="left">Key enzyme in the final step in hydrolysis of cellulose by converting cellobiose to glucose</td>
<td align="left">
<italic>Rhizopus oryzae</italic>
</td>
<td align="left">Solid state fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B155">Karmakar and Ray (2011)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Xylanase</td>
<td rowspan="2" align="left">Paper industries, additive in animal feedstock, food additives, ingredient in detergents, fabric care compositions, and biofuel production</td>
<td align="left">
<italic>Trichoderma reesei</italic>
</td>
<td align="left">Pretreatment &#x2b; fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B83">Manivannan and Narendhirakannan (2014)</xref>
</td>
</tr>
<tr>
<td/>
<td/>
<td align="left">
<italic>Trichoderma species</italic>
</td>
<td align="left">Fermentation</td>
<td align="left">
<xref ref-type="bibr" rid="B134">Udeh et&#x20;al. (2017)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>In the same line, biopolymers are produced by various microorganisms, like <italic>Cupravidus necatar</italic> and <italic>Pseudomonas aeruginosa</italic>, combined with acid pretreatments using <italic>E. crassipes</italic> as a substrate. <xref ref-type="bibr" rid="B98">Radhika and Murugesan (2012)</xref> revealed that the addition of <italic>E. crassipes</italic> enzymatic hydrolizate gave 4.3&#xa0;g/L of&#x20;PHB.</p>
<p>Moreover, different chemical pretreatments along with enzymatic saccharification by <italic>Ralstonia eutropha</italic> yielded 73% of the biopolymer PHB (<xref ref-type="bibr" rid="B150">Saratale et&#x20;al., 2020</xref>).</p>
<p>Meanwhile, the composites are prepared using solution impregnation and hot curving methods (<xref ref-type="bibr" rid="B44">Ramirez et&#x20;al., 2015</xref>). According to several studies, <italic>E. crassipes</italic> has been used as a raw material to produce high-value chemicals such as furfural, enzymes, biopolymers, and composites as reviewed in <xref ref-type="bibr" rid="B49">Guna et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B115">Sindhu et&#x20;al. (2017)</xref>, and <xref ref-type="bibr" rid="B58">Ilo et&#x20;al. (2020)</xref>.</p>
</sec>
<sec id="s6">
<title>Pharmacological and Biological Activities</title>
<p>The varied ethnobotanical uses of <italic>E. crassipes</italic> have led to the ignition of various pharmacological investigations. A diverse range of <italic>in&#x20;vitro</italic> and <italic>in vivo</italic> test systems has been used to evaluate the pharmacological properties of <italic>E. crassipes</italic>. <xref ref-type="table" rid="T3">Table&#x20;3</xref> summarizes the reported pharmacological activities of <italic>E. crassipes</italic>. These include anti-microbial, antioxidant<bold>,</bold> wound healing, antitumor, and cytotoxic activities encompassing more than 50% of the studies. The activities related to larvicidal, insecticidal, and allelopathic effects accounted for 20% of the studies (<xref ref-type="fig" rid="F4">Figure&#x20;4</xref>). The wide range of biological activities of <italic>E. crassipes</italic> are attributed to the presence of bioactive compounds belonging to different classes of secondary metabolites as reported earlier.</p>
<table-wrap id="T3" position="float">
<label>TABLE 3</label>
<caption>
<p>Selected pharmacological activities of <italic>E. crassipes</italic>
<italic>.</italic>
</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Plant part used</th>
<th align="center">Type of extract</th>
<th align="center">Concentration/dosage</th>
<th align="center">Model animal/tested cell/type of study</th>
<th colspan="2" align="center">Findings</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td colspan="7" align="left">
<bold>Toxicity studies</bold>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">50% of methanol</td>
<td align="center">Up to 500&#xa0;mg/kg</td>
<td align="left">
<italic>In vivo</italic>, C57BL male and hybrid from Swiss albino female</td>
<td colspan="2" align="left">No death was observed at 500&#xa0;mg/kg</td>
<td align="left">
<xref ref-type="bibr" rid="B10">Ali et&#x20;al. (2009)</xref>
</td>
</tr>
<tr>
<td rowspan="3" align="left">Leaves and shoot</td>
<td rowspan="3" align="left">Ethyl acetate, water, and methanol</td>
<td rowspan="3" align="center">Up to 2000&#xa0;mg/kg</td>
<td rowspan="3" align="left">
<italic>In vivo</italic>, Swiss albino mice</td>
<td colspan="2" align="left">The tested extracts did not produce any mortality</td>
<td rowspan="3" align="left">
<xref ref-type="bibr" rid="B74">Lalitha and Jayanthi (2012)</xref>
</td>
</tr>
<tr>
<td colspan="2" align="left">LD<sub>50</sub> is higher than 2000&#xa0;mg/kg</td>
</tr>
<tr>
<td colspan="2" align="left">The plant extract had no adverse effect</td>
</tr>
<tr>
<td rowspan="2" align="left">Leaves</td>
<td rowspan="2" align="left">Leaf powder</td>
<td rowspan="2" align="center">DN</td>
<td rowspan="2" align="left">
<italic>In vivo</italic>, Kunming mice</td>
<td colspan="2" align="left">The LD<sub>50</sub> was more than 16&#xa0;g/kg body weight</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B140">Wu et&#x20;al. (2014)</xref>
</td>
</tr>
<tr>
<td colspan="2" align="left">
<italic>E. crassipes</italic> leaf powder did not indicate any adverse effects on organs, behaviors, hematological analysis, and histopathological analysis</td>
</tr>
<tr>
<td colspan="7" align="left">
<bold>Neuroprotective effects</bold>
</td>
</tr>
<tr>
<td rowspan="19" align="left">Leaves</td>
<td rowspan="19" align="left">Ethanol extract</td>
<td rowspan="19" align="center">DN</td>
<td colspan="2" align="left">
<italic>In vivo</italic>, Albino mice</td>
<td align="left">The ethanolic leaf extract exhibits sedative, anti-psychosis, antidepression, and memory enhancing properties</td>
<td rowspan="19" align="left">
<xref ref-type="bibr" rid="B42">Farheen et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td colspan="2" align="left">Number of head dips</td>
<td align="char" char=".">11.25&#x20;&#xb1; 0.25</td>
</tr>
<tr>
<td colspan="2" align="left">Locomotor activity</td>
<td align="char" char=".">47.83%</td>
</tr>
<tr>
<td colspan="2" align="left">Duration of stay on Rotarod</td>
<td align="char" char=".">193.8&#x20;&#xb1; 2.13</td>
</tr>
<tr>
<td colspan="2" align="left">Sleep time</td>
<td align="char" char=".">70.5&#x20;&#xb1; 0.645&#xa0;min</td>
</tr>
<tr>
<td colspan="2" align="left">Number of movements</td>
<td align="char" char=".">3.75&#x20;&#xb1; 0.25</td>
</tr>
<tr>
<td colspan="2" align="left">Hot plate test (reaction time)</td>
<td align="char" char=".">7.25&#x20;&#xb1; 0.25 5 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Acetic acid writing test</td>
<td align="char" char=".">16.25&#x20;&#xb1; 2.056</td>
</tr>
<tr>
<td colspan="2" align="left">Tail flick test</td>
<td rowspan="2" align="char" char=".">1.75&#x20;&#xb1; 0.25 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Tail withdrawal time</td>
</tr>
<tr>
<td colspan="2" align="left">Isoniazid convulsion test</td>
<td align="char" char=".">33.25&#x20;&#xb1; 1.797 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Elevated plus maze test (time spent in open/closed arms)</td>
<td align="char" char=".">199.3&#x20;&#xb1; 13.73/100.8&#x20;&#xb1; 13.73 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Novelty-induced hypophoria (home cage/novel cage)</td>
<td align="char" char=".">62&#x20;&#xb1; 4.708/38.25&#x20;&#xb1; 8.3</td>
</tr>
<tr>
<td colspan="2" align="left">Step down test</td>
<td align="char" char=".">147.3&#x20;&#xb1; 1.377 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Normothermic animals</td>
<td align="char" char=".">36.4&#x20;&#xb1; 0.15&#xa0;&#xb0;C in 60&#xa0;min</td>
</tr>
<tr>
<td colspan="2" align="left">Tail suspension test</td>
<td align="char" char=".">46.56&#x20;&#xb1; 1.033 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Forced swim test</td>
<td align="char" char=".">213&#x20;&#xb1; 5.066 (s)</td>
</tr>
<tr>
<td colspan="2" align="left">Antipsychotic-induced weight gain</td>
<td align="char" char=".">40&#x20;&#xb1; 3.53 (gms)/4&#xa0;weeks</td>
</tr>
<tr>
<td colspan="2" align="left">Catalepsy test</td>
<td align="char" char=".">19.25&#x20;&#xb1; 0.25 (s)</td>
</tr>
<tr>
<td colspan="7" align="left">
<bold>Anti-inflammatory activities</bold>
</td>
</tr>
<tr>
<td rowspan="3" align="left">Leaves and shoot</td>
<td rowspan="3" align="left">Petroleum ether, ethyl acetate</td>
<td rowspan="3" align="center">DN</td>
<td rowspan="3" align="left">
<italic>In vivo</italic>, male Swiss albino mice</td>
<td colspan="2" align="left">The ethyl acetate extract and petroleum ether extract have shown maximum inhibition of edema, 67.5 and 64.81%, respectively</td>
<td rowspan="3" align="left">
<xref ref-type="bibr" rid="B63">Jayanthi et&#x20;al. (2013)</xref>
</td>
</tr>
<tr>
<td colspan="2" align="left">The aqueous extract showed 21.62% inhibition of anti-inflammatory activity</td>
</tr>
<tr>
<td colspan="2" align="left">The plant possesses a strong activity to prevent pains</td>
</tr>
<tr>
<td align="left">The whole plant</td>
<td align="left">Methanol</td>
<td align="center">100&#x2013;500&#xa0;&#x3bc;g/ml</td>
<td align="left">Lab assay</td>
<td colspan="2" align="left">The maximum inhibition of albumin denaturation protein (79%) was observed at 500&#xa0;&#x3bc;g/L of the methanolic extract</td>
<td align="left">
<xref ref-type="bibr" rid="B120">Sunitha et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td colspan="7" align="left">
<bold>Anticancer activities</bold>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">50% Methanol extract</td>
<td align="center">200&#x2013;500&#xa0;m/kg</td>
<td align="left">B16F1 mouse melanoma</td>
<td colspan="2" align="left">The extract has shown antitumor potential when subjected to radiotherapy or alone</td>
<td align="left">
<xref ref-type="bibr" rid="B10">Ali et&#x20;al. (2009)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Leaves</td>
<td rowspan="2" align="left">Crude extract</td>
<td rowspan="2" align="center">DN</td>
<td align="left">Liver cancer cell line</td>
<td colspan="2" align="left">The crude extract and several fractions showed anticancer activity against several tumor types</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B3">Aboul-Enein et&#x20;al. (2011)</xref>
</td>
</tr>
<tr>
<td align="left">Hormone-dependent tumor of cervix and breast cancers</td>
<td colspan="2" align="left">The isolated compound showed potency with IC<sub>50</sub> low than 1.6&#x00B1;0.5&#xa0;&#x3bc;g/mL</td>
</tr>
<tr>
<td align="left">The whole plant</td>
<td align="left">Crude methanolic extract</td>
<td align="center">DN</td>
<td align="left">HeLa, EACC, HepG2, and MCF-7 cell lines</td>
<td colspan="2" align="left">The crude extract showed acceptable potency against HeLa and MCF-7 with IC<sub>50</sub> &#x3d; 1.6 and 1.2, while HepG2 and EACC exhibited higher resistance to the crude extract</td>
<td align="left">
<xref ref-type="bibr" rid="B109">Shanab and Shalaby (2012)</xref>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Methanol</td>
<td align="center">0&#x2013;200&#xa0;&#x3bc;g/ml</td>
<td align="left">Human cervical cancer cell line</td>
<td colspan="2" align="left">As the concentration of the methanolic extract increases, the inhibition of cell growth increased with 17% of growth inhibition at 200&#xa0;&#x3bc;g/ml</td>
<td align="left">
<xref ref-type="bibr" rid="B78">Lenora et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanol</td>
<td align="center">6.25&#x2013;100&#xa0;&#x3bc;g/ml</td>
<td align="left">Breast cancer cell line MCF-7</td>
<td colspan="2" align="left">The leaves extract inhibited the growth of cells with more than 80% pf cell at 100&#xa0;&#xb5;g/mL</td>
<td align="left">
<xref ref-type="bibr" rid="B123">Taqi et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td colspan="7" align="left">
<bold>Thrombolytic activity</bold>
</td>
</tr>
<tr>
<td align="left">Plant</td>
<td align="left">Organic extract (methanol, n-hexane, chloroform, and carbon-tetrachloride</td>
<td align="center">100&#xa0;&#xb5;L</td>
<td align="left">Human blood clots</td>
<td colspan="2" align="left">The % of clot lysis was observed as 23.37% for methanol, 13.98% for hexane, and 19.01% for carbon-tetrachloride</td>
<td align="left">
<xref ref-type="bibr" rid="B59">Islam (2018)</xref>
</td>
</tr>
<tr>
<td colspan="7" align="left">
<bold>Antioxidant activities</bold>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Liquid extracts</td>
<td align="center">DN</td>
<td align="left">N,N-diethyl-l,4-phenylenediamine (DPD) assay</td>
<td colspan="2" align="left">The leaf extracts exhibited a high degree of peroxidase and antioxidant enzyme activities recorded by 0.82 and 0.020 units/mg protein, respectively</td>
<td align="left">
<xref ref-type="bibr" rid="B22">Bodo et&#x20;al. (2004)</xref>
</td>
</tr>
<tr>
<td align="left">The plant</td>
<td align="left">Crude extract</td>
<td align="center">DN</td>
<td align="left">Lab assay (DPPH)</td>
<td colspan="2" align="left">The crude extract showed higher antioxidant activities. The fractions showed close antioxidant effects with IC<sub>50</sub> ranging between 97.0&#x00B1;5.4 and 97.4&#x00B1;2.7&#xa0;&#x3bc;g/ml</td>
<td align="left">
<xref ref-type="bibr" rid="B3">Aboul-Enein et&#x20;al. (2011)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">The whole plant</td>
<td rowspan="2" align="left">Hexane, ethyl acetate, methanol</td>
<td rowspan="2" align="center">50&#x2013;100&#xa0;&#x3bc;g/ml</td>
<td rowspan="2" align="left">Lab assay (DPPH, ABTS)</td>
<td colspan="2" align="left">The antioxidant activity using DPPH is concentration dependent, and it increased with doubling the concentration</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B109">Shanab and Shalaby, (2012)</xref>
</td>
</tr>
<tr>
<td colspan="2" align="left">Using ABTS method, methanol extract showed higher antioxidant scavenging activity followed by hexane and ethyl acetate</td>
</tr>
<tr>
<td rowspan="2" align="left">Leaves</td>
<td rowspan="2" align="left">Ethanol, aqueous, chloroform</td>
<td rowspan="2" align="center">25&#x2013;100&#xa0;&#x3bc;g/ml</td>
<td align="left">Lab assay (FTC)</td>
<td colspan="2" align="left">Ethanol extract showed significant antioxidant activity in all concentration (25&#x2013;100&#xa0;&#x3bc;g/ml)</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B52">Hamid et&#x20;al. (2013)</xref>
</td>
</tr>
<tr>
<td align="left">Lab assay (lipid peroxidation)</td>
<td colspan="2" align="left">At 100&#xa0;&#x3bc;g/ml of ethanol, extract caused inhibition of linoleic acid emulsion with 85.6% in comparison with chloroform extract (64%), and the aqueous extract (28.8%)</td>
</tr>
<tr>
<td align="left">Plant</td>
<td align="left">Methanol, n-hexane, chloroform, and carbon-tetrachloride</td>
<td align="center">3.37&#x2013;100&#xa0;&#x3bc;g/ml</td>
<td align="left">DPPH</td>
<td colspan="2" align="left">The IC<sub>50</sub> values were 0.018, 0.387, and 1.03&#xa0;&#x3bc;g/ml for methanol, n-hexane, chloroform, and carbon-tetrachloride, respectively</td>
<td align="left">
<xref ref-type="bibr" rid="B59">Islam (2018)</xref>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanol/water extract</td>
<td align="center">DN</td>
<td align="left">Lab assay (DPPH)</td>
<td colspan="2" align="left">The highest antioxidant activity was obtained from extraction at 50&#xb0; with ratio 2:1</td>
<td align="left">
<xref ref-type="bibr" rid="B90">Nugriani et&#x20;al. (2020)</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>DN, data not available.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Percentage of the studied biological and pharmacological activities of <italic>E. crassipes</italic> according to the literature.</p>
</caption>
<graphic xlink:href="fphar-13-842511-g004.tif"/>
</fig>
<sec id="s6-1">
<title>Neuropharmacological Activities</title>
<p>Potential behavioral neuropharmacological activities, as evidenced by the analgesic, anti-epileptic sedative, central nervous system depressant, anti-anxiety, anti-psychosis, anti-depressant, and memory-improving properties, were exerted by the ethanol extract of leaves of <italic>E. crassipes</italic> in combination with ethanol extracts of <italic>Nelumbo nucifera</italic> leaves in mice models (<xref ref-type="bibr" rid="B42">Farheen et&#x20;al., 2015</xref>). The results showed that the ethanol extract of <italic>E. crassipes</italic> leaves significantly inhibited motor activity, demonstrated high anti-anxiety property, and decreased the exploratory behavior pattern in evasion tests. The treated mice were able to maintain their posture for over 180&#xa0;s. Moreover, the same extract prolonged sleep latency and duration, improved latency period, and generated the highest inhibition of writhing test induced by acetic acid. In addition, the histopathological findings confirmed the neuronal protective properties of <italic>E. crassipes</italic> in combination with <italic>N. nucifera</italic>, where an important glial reaction was observed in the brain of the treated mice (<xref ref-type="bibr" rid="B42">Farheen et&#x20;al., 2015</xref>). However, there are some shortcomings in the application of <italic>E. crassipes</italic> extracts as a neuroprotective agent. In this line, further studies are required to confirm the neuropharmacological activity of the plant, to clarify the correlation between the phytochemical composition and the pharmacological activity.</p>
</sec>
<sec id="s6-2">
<title>Anti-Inflammatory Activities</title>
<p>The stems and leaves of <italic>E. crassipes</italic> were used to treat swelling and wounds due to its anti-inflammatory activity associated with the phenolic content in the plant (<xref ref-type="bibr" rid="B103">Rorong et&#x20;al., 2012</xref>). In the sample line, lemon juice plus the juice of <italic>E. crassipes</italic> leaves have been traditionally used as anti-inflammatory topical agents in the Philippines (<xref ref-type="bibr" rid="B112">Sharma et&#x20;al., 2020</xref>).</p>
<p>So far, there are only few articles demonstrating the toxicity of <italic>E. crassipes</italic>. The hydroalcoholic extract of the leaves at 500&#xa0;mg/kg showed no death of animals within 14&#xa0;days of administration of extracts (<xref ref-type="bibr" rid="B10">Ali et&#x20;al., 2009</xref>).</p>
<p>The <italic>in vivo</italic> anti-inflammatory activity of ethyl acetate, petroleum ether, and aqueous extracts of the leaves and shoot parts of the plant were studied on formaldehyde-induced paw edema. Among the studied extracts, the ethyl acetate extract showed the best anti-inflammatory activity with 67.5% of inhibition of paw edema. This anti-inflammatory activity would be related to the presence of anthocyanins and phenolic compounds (<xref ref-type="bibr" rid="B62">Jayanthi et&#x20;al., 2011</xref>). Moreover, the investigation of the <italic>in&#x20;vitro</italic> anti-inflammatory activity of the methanol extract of <italic>E. crassipes</italic> by the inhibition of albumin denaturation technique demonstrated a maximum inhibition of 79% at a concentration of 500&#xa0;&#x3bc;g/ml (<xref ref-type="bibr" rid="B120">Sunitha et&#x20;al., 2018</xref>). This activity could be attributed to the presence of sterols, especially stigmasterol, which has a role as an anti-inflammatory compound. Furthermore, the compound could be used as a precursor to produce other bioactive compounds for medical purposes (<xref ref-type="bibr" rid="B156">Paniagua-P&#xe9;rez et&#x20;al., 2008</xref>).</p>
</sec>
<sec id="s6-3">
<title>Hepatoprotective Activities</title>
<p>Different parts of <italic>E. crassipes</italic> have been used as a traditional herbal remedy for its beneficial effects on human diseases. In Bangladesh, the roots and flowers are used in the treatment of hepatic disorders and abdominal swelling (<xref ref-type="bibr" rid="B99">Rahmatullah et&#x20;al., 2010</xref>).</p>
<p>The methanolic extract of <italic>E. crassipes</italic> demonstrated hepatoprotective activity against CCl<sub>4</sub>-induced hepatotoxicity in rats. The plant extract was effective in protecting the liver at 400&#xa0;mg/kg against injury induced by CCl<sub>4</sub> in rats manifested by a significant reduction in bilirubin (TB &#x3d; 0.05&#xa0;mg/Dl), serum glutamic oxaloacetic transaminase (SGOT &#x3d; 293&#xa0;IU/L), serum glutamic&#x2013;pyruvic transaminase (SGPT &#x3d; 238&#xa0;IU/L), and alkaline phosphatase (ALP &#x3d; 169&#xa0;IU/L) when compared with CCl<sub>4</sub>-alone treated rats (TB &#x3d; 0.23&#xa0;mg/Dl, SGOT &#x3d; 567&#xa0;IU/L, SGPT &#x3d; 747&#xa0;IU/L, ALP &#x3d; 344&#xa0;IU/L, respectively) (<xref ref-type="bibr" rid="B40">Dineshkumar et&#x20;al., 2013</xref>).</p>
<p>Furthermore, <italic>E. crassipes</italic> was shown to have an effective hepatoprotective agent by virtue of its <italic>in vivo</italic> effect on liver markers and in combating oxidative stress as well, where the coadministration of the leaves aqueous extract with isoniazid in rats exhibited a 46% reduction in malondialdehyde level with concomitant elevation in the total antioxidant value of the plasma (21%). Furthermore, <italic>E. crassipes</italic> leaf aqueous extract at 400&#xa0;mg/kg restored the hepatic marker levels in the serum, like alkaline phosphatase (69.22%), SGOT (29%), SGPT (62.31%), creatinine (108.80%), complete bilirubin (48.95%), and hemoglobin (65.69%) (<xref ref-type="bibr" rid="B71">Kumar et&#x20;al., 2014</xref>). Therefore, rat models of liver injury should be investigated more to confirm the effect of <italic>E. crassipes</italic> as a liver protector&#x20;agent.</p>
</sec>
<sec id="s6-4">
<title>Antitumor/Cytotoxic Activities</title>
<p>
<italic>E. crassipes</italic> is known to contain some therapeutic compounds such as alkaloids and terpenoids that display anticancer properties (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>). The antitumor activity of 50% methanolic extract of <italic>E. crassipes</italic> at different doses showed a good response against melanoma tumor&#x2013;bearing hybrid mice (<xref ref-type="bibr" rid="B10">Ali et&#x20;al., 2009</xref>). The crude methanolic extract of the whole plant also revealed a notable potency against MCF-7, HeLa cells, EACC, and HepG2 cell lines with IC<sub>50</sub> values of 1.2&#x20;&#xb1; 0.2, 1.6&#x20;&#xb1; 0.5, 6.04&#x20;&#xb1; 0.5, and 7.6&#x20;&#xb1; 1.5&#xa0;&#x3bc;g/ml, respectively, compared to doxorubicin, a standard drug that revealed 0.28&#xa0;&#x3bc;g/ml for HeLa and 0.42&#xa0;&#x3bc;g/ml for both MCF-7 and HepG2 cell lines (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>). The aqueous leaf extract of <italic>E. crassipes</italic> displayed 44% inhibition against the NCI-H322 cell line and 20&#x2013;31% cytotoxic activity against the T47D cell line. However, A549 and PC3 cell lines displayed resistance to <italic>E. crassipes</italic> extracts (<xref ref-type="bibr" rid="B71">Kumar et&#x20;al., 2014</xref>). Di-amino-di-nitro-methyl dioctyl phthalate (73) and 9-(2&#x2032;,2&#x2032;-dimethyl-propanoilhydrazono)-2,7-bis-[2-(diethylamino)-ethoxy]fluorene (74) showed a different cytotoxic activity to different extents (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>; <xref ref-type="bibr" rid="B87">Mtewa et&#x20;al., 2018</xref>). However, no experiments using <italic>in vivo</italic> cancer models were investigated. Thus, preclinical and clinical studies are required to assess the safety and efficacity of bioactive compounds.</p>
</sec>
<sec id="s6-5">
<title>Antioxidant Activities</title>
<p>
<italic>E. crassipes</italic> induces substantial antioxidant activities, and it is confirmed to be a great source of natural antioxidants (<xref ref-type="bibr" rid="B74">Lalitha and Jayanthi, 2012</xref>). The plant is a source of many compounds with radical scavenging activity, such as phenolic acids, sterols, terpenoids, and other metabolites with high antioxidant activity (<xref ref-type="bibr" rid="B133">Tyagi and Agarwal, 2017a</xref>).</p>
<p>Ethanol extracts from the leaves exerted robust Fe<sup>2&#x2b;</sup> chelating activity. Meanwhile, the ethanolic extract of the flowers with a high content of phenolic compounds exhibited a substantial reducing power and radical scavenging activity (<xref ref-type="bibr" rid="B121">Surendraraj et&#x20;al., 2013</xref>). In addition, the antioxidant properties of the methanolic crude extract of the whole plant and its isolated compounds, the alkaloids and terpenoids derivatives, were studied using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity. As results the crude extract showed a good antioxidant activity while some compounds such as 1,2-benzene dicarboxylic acid, dioctyl ester (131), 1,2-benzene dicarboxylic acid, diisooctyl ester (132), 3-methyl-phenyl)-phenylmethanol (133), 4-(diethylamino)-alpha-[4-(diethylamino) phenyl] (134), and 9-(2&#x2032;,2&#x2032;-dimethyl-propanoilhydrazono)-2,7-bis-[2-(diethylamino)-ethoxy]fluorene (74) recorded moderate activities with IC<sub>50</sub> ranging between 97.0&#x20;&#xb1; 5.4 and 97.4&#x20;&#xb1; 2.7&#xa0;&#x3bc;g/ml (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>). The high antioxidant potential of the methanolic crude extract could be explained by virtue of the synergistic activities of all bioactive compounds (<xref ref-type="bibr" rid="B4">Aboul-Enein et&#x20;al., 2014</xref>). <italic>E. crassipes</italic> extracts have shown encouraging antiaging effects, as determined through DNA damage inhibition and DPPH radical scavenging assays. There was a pronounced increase in the DNA damage inhibition and DPPH radical scavenging ability with an increase in the concentration of ethyl acetate extracts of the plant (<xref ref-type="bibr" rid="B73">Lalitha and Jayanthi, 2014</xref>). Moreover, the highest radical scavenging activity was observed in the petiole with an IC<sub>50</sub> value &#x3d; 6.411&#x20;&#xb1; 0.46&#xa0;mg/ml as compared with IC<sub>50</sub> &#x3d; 0.516&#x20;&#xb1; 0.22&#xa0;mg/ml obtained by the reference compound&#x2014;the gallic acid (<xref ref-type="bibr" rid="B132">Tyagi and Agarwal, 2017b</xref>).</p>
<p>The methanolic extract of <italic>E. crassipes</italic> showed good DPPH radical scavenging activity with a maximum inhibition of 78% at 250&#xa0;&#x3bc;g/ml, while in hydrogen peroxide scavenging activity, the maximum inhibition was 80% observed at 250&#xa0;&#x3bc;g/ml; ascorbic acid, a standard antioxidant drug demonstrated a maximum inhibition of 69% and 68% in both tests at 100&#xa0;&#x3bc;g/ml, respectively (<xref ref-type="bibr" rid="B120">Sunitha et&#x20;al., 2018</xref>). In the same line, methanol, n-hexane, and carbon tetrachloride extracts of the leaves demonstrated free radical scavenging activity with IC<sub>50</sub> of 0.018, 0.387, and 1.03&#xa0;&#x3bc;g/ml, respectively (<xref ref-type="bibr" rid="B59">Islam, 2018</xref>). Recently, the antioxidant properties of the leaf protein hydrolysates indicated excellent antioxidant activities, especially the two peptides that have shown high radical scavenging activities with 86.37% of superoxide anion radical scavenging activity at 1&#xa0;mg/ml and 56.51% of ABTS cation radical scavenging activity at 100&#xa0;&#x3bc;g/ml (<xref ref-type="bibr" rid="B144">Zhang et&#x20;al., 2018</xref>). However, quercetin 7-methyl ether (30) isolated from the whole plant exhibited weak antioxidant activities using DPPH method, with an IC<sub>50</sub> &#x3d; 254.66&#xa0;&#x3bc;g/ml compared with quercetin (IC<sub>50</sub> &#x3d; 23.24&#xa0;mg/ml) (<xref ref-type="bibr" rid="B41">Elvira et&#x20;al., 2018</xref>). Thus, additional <italic>in vivo</italic> studies are required to confirm the important effect demonstrated by <italic>in&#x20;vitro</italic> studies, to determine the molecular mechanisms of the extracts and the bioactive compounds found in <italic>E. crassipes</italic>.</p>
</sec>
<sec id="s6-6">
<title>Antimicrobial Activities</title>
<p>Many extracts of <italic>E. crassipes</italic> demonstrated antibacterial and antifungal activities (<xref ref-type="table" rid="T4">Table&#x20;4</xref>).</p>
<table-wrap id="T4" position="float">
<label>TABLE 4</label>
<caption>
<p>Bactericidal and antifungal potential of various extracts of <italic>E. crassipes.</italic>
</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Plant part used</th>
<th align="center">Nature of extract</th>
<th align="center">Bacteria studied</th>
<th align="center">Fungal strains</th>
<th align="center">Method adapted</th>
<th align="center">Findings</th>
<th align="center">Standard drug</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">The whole plant</td>
<td align="left">n-hexane</td>
<td align="left">
<italic>Salmonella typhi</italic>, <italic>Klebsiella pneumoniae</italic>, <italic>Agrobacterium tumifaciens</italic>, <italic>B. subtilis</italic>, <italic>B. atrophaeus</italic>, <italic>E.&#x20;coli</italic>, <italic>S. aureus</italic>, and <italic>P. aeruginosa</italic>
</td>
<td align="left">
<italic>C. albicans</italic>
</td>
<td align="left">Disk diffusion method</td>
<td align="left">The n-hexane extract was active against all tested pathogenic bacteria except <italic>S. typhi</italic>, The extract was also active against <italic>C. albicans</italic>. The antibacterial activity was comparable to the used standards</td>
<td align="left">Erythromycin, Clotrimazole, Ciprofloxacin</td>
<td align="left">
<xref ref-type="bibr" rid="B42">Farheen et&#x20;al. (2015)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Flowers</td>
<td rowspan="2" align="left">Methanol extract</td>
<td rowspan="2" align="left">
<italic>S. aureus</italic> MTCC 23313, <italic>Vibrio cholerae</italic> MTCC 1957</td>
<td rowspan="2" align="left">
<italic>-</italic>
</td>
<td rowspan="2" align="left">Disk diffusion method</td>
<td align="left">The methanolic floral extract possess significant antibacterial activity at 20&#xa0;&#x3bc;g/ml against the tested bacteria</td>
<td rowspan="2" align="left">-</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B113">Shehnaz and Vijayalakshmi, (2016)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>S. aureus</italic> was found to be more sensitive compared to <italic>V. cholerae</italic>
</td>
</tr>
<tr>
<td rowspan="2" align="left">Leaves</td>
<td rowspan="2" align="left">Methanolic extract</td>
<td align="left">Coagulase-negative <italic>Staphylococcus epidermidis</italic> (CoNS1, CoNS2, and CoNS3), methicillin-resistant <italic>S. aureus</italic> (MRSA1 and MRSA2)</td>
<td rowspan="2" align="left">-</td>
<td rowspan="2" align="left">Disk diffusion method</td>
<td align="left">A maximum zone of inhibition &#x3d; 14.63&#x20;&#xb1; 0.16&#xa0;mm at 1,000&#xa0;&#x3bc;g/ml</td>
<td rowspan="2" align="left">Oxacillin</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B50">Guti&#xe9;rrez-Morales et&#x20;al. (2017)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>S. aureus</italic> ATCC 25923, <italic>S. aureus</italic> ATCC 29213, <italic>S. aureus</italic> ATCC 43300, oxacillin-sensitive <italic>S. aureus</italic> (SOSA1 and SOSA2)</td>
<td align="left">A minimum zone of inhibition of 10.17&#x20;&#xb1; 0.35&#xa0;mm was observed against <italic>S. aureus</italic> TCC 43300</td>
</tr>
<tr>
<td rowspan="2" align="left">Water hyacinth biomass</td>
<td rowspan="2" align="left">Acetone, n-butyl alcohol, distilled water ethanol, and methanol</td>
<td rowspan="2" align="left">
<italic>B. subtilis</italic>, <italic>B. cereus</italic>, <italic>E.&#x20;coli</italic>, <italic>L. casei</italic>, <italic>P. aeruginosa</italic>
</td>
<td align="left">
<italic>A. flavus</italic>, <italic>A. niger</italic>, <italic>A. alternata</italic>, <italic>C. albicans</italic>
</td>
<td rowspan="2" align="left">Serial tube dilution technique</td>
<td align="left">MIC &#x3d; (8&#x2013;64&#xa0;&#x3bc;g/ml) against all tested bacteria and fungi</td>
<td rowspan="2" align="left">Streptomycin and Fluconazole</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B51">Haggag et&#x20;al. (2017)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>Colletotrichum gloeosporioides</italic>, <italic>Fusarium solani</italic>
</td>
<td align="left">However, n-butanol and methanol have the most effective activities against <italic>Gloeosporioides</italic>, <italic>F. solani</italic>, and <italic>B. Subtilis</italic>
</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanolic and methanolic extracts</td>
<td align="left">
<italic>S. aureus</italic> (ATCC-25923), <italic>Salmonella typhi</italic> (ATCC13311), <italic>Shigella boydii</italic> (ATCC-9202), and <italic>E.&#x20;coli</italic> O157:H7 (ATCC13242)</td>
<td align="left"/>
<td align="left">Disk diffusion method</td>
<td align="left">The antibacterial activity of the ethanolic leaf extracts of <italic>E. crassipes</italic> at 100&#xa0;mg/ml, 125&#xa0;mg/ml, and 150&#xa0;mg/ml against all tested bacterial strains exhibited significant zone of inhibition against the gram-positive bacteria <italic>S. aureus</italic> (12&#x2013;18&#xa0;mm) and moderate zone of inhibition against the selected gram-negative bacteria such as <italic>S. typhi</italic> (10&#x2013;14&#xa0;mm), <italic>S. boydii</italic> (10&#x2013;14&#xa0;mm), and <italic>E.&#x20;coli</italic> (9&#x2013;16&#xa0;mm)</td>
<td align="left">Amoxicillin</td>
<td align="left">
<xref ref-type="bibr" rid="B68">Kiristos et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td align="left">Water hyacinth leaves</td>
<td align="left">Hydro-methanolic extract</td>
<td align="left">Human and aquatic pathogens</td>
<td align="left">
<italic>-</italic>
</td>
<td align="left">Disk diffusion test</td>
<td align="left">The antimicrobial activity significantly increased against <italic>E.&#x20;coli</italic> in hydro-methanolic extract and against <italic>S. iniae</italic> in the aqueous extract. The MIC and MBC were 64&#x2013;256&#xa0;mg/ml and 128&#x2013;512&#xa0;mg/ml, respectively</td>
<td align="left">-</td>
<td align="left">
<xref ref-type="bibr" rid="B105">Rufchaie et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td rowspan="5" align="left">Biomass</td>
<td rowspan="5" align="left">Ethanol and chloroform extract</td>
<td align="left">
<italic>S. aureus</italic> ATCC 25923</td>
<td align="left">
<italic>Aspergillus flavus NRRL 1957&#x2014;Aspergillus niger NRRL 326</italic>
</td>
<td rowspan="5" align="left">Disk diffusion method</td>
<td align="left">IZD &#x3d; 8 and 21.5&#xa0;mm for <italic>S. aureus</italic> in both extracts</td>
<td rowspan="5" align="left">-</td>
<td rowspan="5" align="left">
<xref ref-type="bibr" rid="B8">Ahmed et&#x20;al. (2018)</xref>
</td>
</tr>
<tr>
<td align="left">
<italic>Bacillus cereus ATCC 33018</italic>
</td>
<td align="left">
<italic>Candida albicans ATCC 10231</italic>
</td>
<td align="left">IZD &#x3d; 6.3&#xa0;mm for <italic>Listeria</italic> by the 5% ethanol extract</td>
</tr>
<tr>
<td align="left">
<italic>Pseudomonas aeruginosa</italic> ATCC 9027</td>
<td align="left">
<italic>Fusarium oxysporum</italic>
</td>
<td align="left">IZD &#x3d; 18,7&#xa0;mm for <italic>B. cereus</italic> by 10% of ethanol extract</td>
</tr>
<tr>
<td align="left">
<italic>Escherichia coli</italic> O157 93111, <italic>Listeria monocytogenes</italic> ATCC 7644</td>
<td align="left">
<italic>Fusarium monilfarum Macrophomina phaseolina</italic>
</td>
<td align="left">IZD &#x3d; 26.0 and 20.2&#xa0;mm for <italic>A. flavus</italic> NRRL 1957</td>
</tr>
<tr>
<td align="left"/>
<td align="left">
<italic>Rhizoctonia solani</italic>
</td>
<td align="left">IZD &#x3d; 16.0 and 9.5&#xa0;mm for <italic>M. phaseolina</italic> at 5% chloroform and <italic>R. solani</italic> at 10% ethanol</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanol extract</td>
<td align="left">
<italic>Aggregatibacter actinomycetemcomitans</italic>
</td>
<td align="left">-</td>
<td align="left">Serial tube dilution technique</td>
<td align="left">No growth of <italic>A. actinomycetemcomitans</italic> at concentrations of 100%&#x2013;6.25% leaf extract</td>
<td align="left">-</td>
<td align="left">
<xref ref-type="bibr" rid="B7">Afidati et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td rowspan="2" align="left">The plant</td>
<td rowspan="2" align="left">Hexane, aqueous, chloroform, methanolic extracts, and ethyl acetate</td>
<td rowspan="2" align="left">
<italic>S. aureus</italic>, <italic>Streptococcus mutans</italic>, <italic>Serratia marcescens</italic>, <italic>Methicillin-resistant Staphylococcus aureus</italic>
</td>
<td rowspan="2" align="left">
<italic>Aspergillus flavous</italic>, <italic>Alternaria alternate</italic>, <italic>Fusarium oxysporum</italic>, <italic>Polysphondylium pallidum</italic>
</td>
<td rowspan="2" align="left">Disk diffusion method</td>
<td align="left">The n-hexane fraction showed a ZOI &#x3d; 11&#x20;&#xb1; 0.66 to 14&#x20;&#xb1; 0.93&#xa0;mm with 46&#x2013;48% of inhibition, while the crude methanolic extracts revealed (38&#x2013;44%) of inhibition against the selected bacteria</td>
<td rowspan="2" align="left">-</td>
<td rowspan="2" align="left">
<xref ref-type="bibr" rid="B136">Wali et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td align="left">ZOI &#x3d; 39.0&#x20;&#xb1; 0.14&#x2013;68.0&#x20;&#xb1; 0.53 for the crude methanolic extracts against the fungal species while the aqueous fractions displayed 15.0&#x20;&#xb1; 0.12 to 25.0&#x20;&#xb1; 0.23&#xa0;mm</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanol</td>
<td align="left">
<italic>S. aureus</italic>, <italic>Escherichia coli</italic>
</td>
<td align="left">
<italic>-</italic>
</td>
<td align="left">Disk diffusion method</td>
<td align="left">The ethanolic extract exhibited good antibacterial activity against <italic>S. aureus</italic>, better than the activity against <italic>E.&#x20;coli</italic> with ZOI more than 15&#xa0;mm at 500&#xa0;&#x3bc;g/ml</td>
<td align="left"/>
<td align="left">
<xref ref-type="bibr" rid="B123">Taqi et&#x20;al. (2019)</xref>
</td>
</tr>
<tr>
<td rowspan="4" align="left">Root, stem, and leaf</td>
<td rowspan="4" align="left">Petroleum ether, chloroform, methanol, and aqueous</td>
<td rowspan="4" align="left">
<italic>Xanthomonas axonopodis</italic>, <italic>Bordetella pertussis</italic>
</td>
<td rowspan="4" align="left">-</td>
<td rowspan="4" align="left">Disk diffusion method</td>
<td rowspan="4" align="left">ZOI &#x3d; 17&#xa0;mm recorded in leaf methanol extract against <italic>B. pertussis</italic>; ZOI &#x3d; (29&#xa0;mm) recorded in chloroform extract against <italic>B. cinerea</italic>
</td>
<td align="left">Ampicillin</td>
<td rowspan="4" align="left">
<xref ref-type="bibr" rid="B67">Khalid et&#x20;al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Amikacin</td>
</tr>
<tr>
<td align="left">Fluconazole</td>
</tr>
<tr>
<td align="left">Kanamycin</td>
</tr>
<tr>
<td align="left">Leaves</td>
<td align="left">Ethanol extract</td>
<td align="left">Subgingival plaque bacteria colony</td>
<td align="left">
<italic>Penicillium italicum</italic>, <italic>Botrytis cinerea</italic>
</td>
<td align="left">Serial tube dilution technique</td>
<td align="left">No growth of subgingival plaque bacteria in groups of 100%, 50%, 25%, 12.5%, and 6.25%. The growth was only seen at 3.125% and the number of bacteria colonies increased at 1.56%</td>
<td align="left">-</td>
<td align="left">
<xref ref-type="bibr" rid="B13">Arismawati et&#x20;al. (2021)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>In Ethiopia, it has been used for the preparation of crude medicine for treating numerous kinds of virulent diseases related to bacterial infections (<xref ref-type="bibr" rid="B68">Kiristos et&#x20;al., 2018</xref>). In fact, the presence of saponins in the leaves makes them a good candidate, with notable biopotency, as an antimicrobial agent. <xref ref-type="bibr" rid="B50">Guti&#xe9;rrez-Morales et&#x20;al. (2017)</xref> revealed the potential of <italic>E. crassipes</italic> leaf extract in combating staphylococcal infections, against methicillin-resistant <italic>S. aureus</italic> (MRSA) found in cattle and Coagulase-negative staphylococci (CoNS) in rabbits. The inhibition of the growth (61.7&#x2013;68.6%) and division of bacteria could be due to the saponins glycosides and their aglycones (<xref ref-type="bibr" rid="B50">Guti&#xe9;rrez-Morales et&#x20;al., 2017</xref>).</p>
<p>
<italic>E. crassipes</italic> displayed antibacterial activities against <italic>S. faecalis</italic>, <italic>E.&#x20;coli</italic>, and <italic>S. aureus</italic>. Meanwhile, developments of <italic>A. niger</italic>, <italic>A. flavus</italic>, and <italic>C. albicans</italic> were repressed by the plant through crude extract or its fractions (<xref ref-type="bibr" rid="B107">Shanab et&#x20;al., 2010</xref>). The water extract of the leaves demonstrated antimicrobial activity as well (zone of inhibition, 8&#x2013;22&#xa0;mm) against <italic>Bordetella bronchiseptica</italic>, <italic>Proteus vulgaris</italic>, and <italic>Salmonella typhi</italic> (<xref ref-type="bibr" rid="B71">Kumar et&#x20;al., 2014</xref>).</p>
<p>In addition, the antibacterial activities of silver nanoparticles, synthesized biologically from the extract of <italic>E. crassipes</italic>, were checked against selected gram-positive and gram-negative bacteria, and significant zones of inhibition were observed (ZOI ranged between 13 and 18&#xa0;mm) (<xref ref-type="bibr" rid="B25">Kiruba Daniel et&#x20;al., 2012</xref>; <xref ref-type="bibr" rid="B128">Thombre et&#x20;al., 2014</xref>). <xref ref-type="bibr" rid="B65">Joshi and Kaur (2013)</xref> investigated the antimicrobial activity of hydroalcoholic and ethanolic extracts on <italic>E.&#x20;coli</italic>, <italic>S. epidermidis</italic>, <italic>P. aeruginosa</italic>, and <italic>B. subtilis</italic> (<xref ref-type="table" rid="T4">Table&#x20;4</xref>). The antifungal effects of the shoots and leaves of the ethanol extracts were evaluated against two fungi, <italic>A. fumigates</italic> and <italic>M. ruber</italic>, employing the disk diffusion method. They revealed notable activity (ZOI &#x3d; 11 and 12&#xa0;mm, respectively) toward all the tested organisms comparable to the standard cotrimaxozole (ZOI &#x3d; 16 and 18&#xa0;mm) (<xref ref-type="bibr" rid="B126">Thamaraiselvi and Jayanthi, 2012</xref>). Furthermore, the antifungal and antibacterial effects of different extracts of the plant against seven phytopathogenic fungi and 11 clinical bacteria showed that the most susceptible organisms were <italic>K. pneumoniae, S. typhi, S. rolfsii</italic>, and <italic>F. moniliforme</italic>. The methanolic fraction was more effective (54.45%) against the bacterial strains as compared to the cold aqueous extract (<xref ref-type="bibr" rid="B19">Baral and Vaidya, 2011</xref>). It has been noted that aqueous extracts of the leaves contained active compounds such as chlorogenic acid, alkaloids, flavonoids, sterols, anthocyanins, and quinones, which significantly improved resistance against pathogen <italic>Lactococcus garvieae</italic> in prawn (Jayanthi et&#x20;al., 2011; <xref ref-type="bibr" rid="B27">Chang and Cheng, 2016</xref>). The ethyl acetate extracts prepared from the stems showed significant antimicrobial activity at 2&#xa0;mg against <italic>S.&#x20;aureus</italic> and <italic>S. typhi</italic> (activity index &#x3d; 0.21 and 0.23, respectively)<italic>.</italic> While the ethyl acetate extracts of the leaves, at the same concentration, were only active against <italic>S. typhi</italic> with an activity index of 0.24 (<xref ref-type="bibr" rid="B54">Hossain et&#x20;al., 2018</xref>). The n-butyl alcohol extract exhibited antimicrobial activities against some bacteria including <italic>E.&#x20;coli</italic>, <italic>B. cereus</italic>, <italic>L. casei</italic>, and <italic>B. subtilis</italic> (MIC &#x3d; 16&#xa0;&#x3bc;g/ml) and antifungal activity against six pathogenic fungi: <italic>A. flavus</italic>, <italic>A. niger</italic>, <italic>A. alternata</italic>, <italic>C. gloeosporioides</italic>, <italic>C. albicans</italic>, and <italic>F. solani</italic> (minimum inhibitory concentration ranged between 8 and 32&#xa0;&#x3bc;g/ml) (<xref ref-type="bibr" rid="B51">Haggag et&#x20;al., 2017</xref>). Concerning staphylococcal contaminations, <italic>E. crassipes</italic> showed a high potency against MRSA found in cows, oxacillin-sensitive <italic>S. aureus</italic> (SOSA), and coagulase-negative <italic>S. epidermidis</italic> (CoNS) present in bunnies (<xref ref-type="bibr" rid="B50">Guti&#xe9;rrez-Morales et&#x20;al., 2017</xref>). The <italic>in silico</italic> antibacterial activity of stigmasterol, 1-monolinoleoylglycerol trimethylsilyl ether, 17-pentatriacontene, and octasiloxane phytocompounds from <italic>E. crassipes</italic> leaves was assessed by the inhibition of AprX enzyme through molecular docking. The results showed that the phytocompounds are strong inhibitors of AprX enzyme with better degrees of docking and interaction analysis (<xref ref-type="bibr" rid="B70">Kumar et&#x20;al., 2018b</xref>). Moreover, the antibacterial activity of iron oxide nanoparticles (FeNPs) synthesized using the leaf extract of the plant was determined using well diffusion method. The FeNPs showed good antibacterial activity with the highest zone of inhibition at 100&#xa0;&#x3bc;g/ml against <italic>Staphylococcus aureus</italic> (23.3&#xa0;mm) and <italic>Pseudomonas fluorescens</italic> (22.6&#xa0;mm) (<xref ref-type="bibr" rid="B60">Jagathesan and Rajiv, 2018</xref>).</p>
<p>
<italic>E. crassipes</italic> water leaf extract showed totally bacteriostatic and bactericidal activities at concentrations of 6.25&#x2013;100%, against <italic>Aggregatibacter actinomycetemcomitans</italic>, a gram-negative bacterium and the major cause of aggressive periodontitis, at a minimal concentration of 1.56% (<xref ref-type="bibr" rid="B7">Afidati et&#x20;al., 2019</xref>). From all studies, it can be concluded that the process of extractions and the type of solvent used could affect the microbial activity of <italic>E. crassipes</italic>.</p>
</sec>
<sec id="s6-7">
<title>Wound Healing Activity</title>
<p>
<italic>E. crassipes</italic> could be used in cosmeceutical preparations because of its wound healing efficiency.</p>
<p>In Nigeria, the plant is used for skin care applications (<xref ref-type="bibr" rid="B1">Abd El-Ghani, 2016</xref>). Moreover, the leaf extract of the plant combined with turmeric and rice flour were used to treat eczema. This activity is due to the significant levels of vitamin C reported in the plant (<xref ref-type="bibr" rid="B112">Sharma et&#x20;al., 2020</xref>).</p>
<p>The methanol extract of <italic>E. crassipes</italic> leaves was formulated as an ointment using 10 and 15% of leaf extracts and had significantly improved wound contraction potential compared to the control due to the presence of phenolic compounds (<xref ref-type="bibr" rid="B9">Ali et&#x20;al., 2010</xref>). In the same line, the plant extracts demonstrated encouraging antiaging effects through DNA damage inhibition. The ethyl acetate extract of the <italic>E. crassipes</italic> plant, in combination with musk and lemon, was formulated as a cream and revealed 8&#x2013;11% tyrosinase inhibition with skin whitening effects. Furthermore, the inhibition of DNA damage was correlated with the increase in concentration of the ethyl acetate extracts (<xref ref-type="bibr" rid="B73">Lalitha and Jayanthi, 2014</xref>). More attention and effort should be given to the investigation of the wound healing effect and the underlining molecular mechanisms for promising cosmeceutical industry prospects.</p>
</sec>
</sec>
<sec id="s7">
<title>Other Biological Activities</title>
<sec id="s7-1">
<title>Larvicidal Activity</title>
<p>
<italic>E. crassipes</italic> displayed effective larvicidal activity in which the crude root extract showed effects on <italic>Chironomus ramosus</italic> eggs and larvae in addition to the toxic potential of the acetone extract toward the two pests <italic>Achaea janata</italic> (LD<sub>50</sub> &#x3e; 100&#xa0;mg/21&#xa0;m<sup>2</sup>/larva) and <italic>Spodoptera litura</italic> (Fab.) (LD<sub>50</sub> &#x3d; 93&#xa0;mg/21&#xa0;m<sup>2</sup>/larva) (<xref ref-type="bibr" rid="B39">Devanand and Rani, 2008</xref>). The ethanol extract of <italic>E. crassipes</italic> leaves and shoot showed higher larvicidal activity against <italic>C. quinquefasciatus</italic> (LC<sub>50</sub> &#x3d; 71.43, 94.68, 120.42, and 152.15&#xa0;ppm) compared to other solvent extracts. This activity might be due to the presence of metabolites like anthraquinones, alkaloids, and flavonoids (<xref ref-type="bibr" rid="B61">Jayanthi et&#x20;al., 2012</xref>). Sterols, sitosterol, have been reported to possess larvicidal activity (<xref ref-type="bibr" rid="B2">Rahuman et&#x20;al., 2008</xref>). The crude ethyl acetate, hexane, methanol, and aqueous leaf extracts were tested for larvicidal effects against the early fourth instar larvae of <italic>C. quinquefasciatus.</italic> The results showed that hexane and methanol extracts were the most effective at doses of 62.5 and 500&#xa0;mg/L with an LC<sub>50</sub> value of 80.54 and 137.50&#xa0;mg/L, respectively (<xref ref-type="bibr" rid="B12">Annie et&#x20;al., 2015</xref>). Furthermore, the effect of the plant infusions on mosquito attractiveness and stimulation of oviposition was investigated, and the results suggested that the plant emits volatile chemicals, such as terpenoids and fatty acid derivatives that attract <italic>A. aegypti</italic> and <italic>A. quadrimaculatus</italic>, and stimulates the egg rafts position of <italic>C. quinquefasciatus</italic> (<xref ref-type="bibr" rid="B131">Turnipseed et&#x20;al., 2018</xref>).</p>
</sec>
<sec id="s7-2">
<title>Allelopathic Effect</title>
<p>The extracts from the sterilized culture of <italic>E. crassipes</italic> were tested for their inhibition of <italic>Chlamydomonas reinhardtii</italic>. At a low concentration, the extract did not inhibit the growth of <italic>C. reinhardtii</italic>. However, inhibition increased at higher concentrations of the exudate since 100&#xa0;&#xb5;L of the extract exhibited 100% inhibition (<xref ref-type="bibr" rid="B119">Sun et&#x20;al., 1990</xref>). Sterols, isolated from the ethyl acetate extract of the plant, were tested for their phytotoxic activity on radish root growth. 4&#x3b1;-methyl-5&#x3b1;-ergosta-8,24(28)-diene-3&#x3b2;,4&#x3b2;-diol and 4&#x3b1;-methyl-5&#x3b1;-ergosta-8,14,24(28)-triene-36,48-diol inhibited, respectively, 40% and 30% of radish root elongation at 6&#xa0;&#xb5;mol (<xref ref-type="bibr" rid="B33">DellaGreca et&#x20;al., 1991</xref>).</p>
<p>Linoleic acid (44), glycerol-1,9-12(ZZ)-octadecadienoic ester (125), and N-phenyl-2-naphthylamine (126) isolated from the acetone extract of the roots showed a stronger anti-algal effect than the common algaecide CuSO<sub>4</sub> (<xref ref-type="bibr" rid="B111">Shanyuan et&#x20;al., 1992</xref>). The crude extract of <italic>E. crassipes</italic> and its fractions exhibited some anti-algal activity against the green microalgae: <italic>Dictyochloropsis splendida</italic> and <italic>Chlorella vulgaris</italic>. This activity was high against <italic>Chlorella vulgaris</italic> (ZOI &#x3d; 18&#x2013;33&#xa0;mm) and could be attributed to the presence of phthalate derivatives and alkaloids (<xref ref-type="bibr" rid="B107">Shanab et&#x20;al., 2010</xref>).</p>
<p>
<xref ref-type="bibr" rid="B141">Wu et&#x20;al. (2012)</xref> investigated the allelopathic effect of the plant against <italic>Microcystis aeruginosa</italic> using coexistence assay. As a result, the growth of the blue-green algae root system was significantly inhibited by the hydroalcoholic extract of the plant. By contrast, no allelopathic effect of the plant on spinach growth was noticed (<xref ref-type="bibr" rid="B20">Barman et&#x20;al., 2006</xref>).</p>
<p>Moreover, the phytotoxic effect of the leaves extract of the plant was assessed against <italic>Mimosa pigra</italic> (an invasive weed) and <italic>Vigna radiata</italic> (a crop species). The results of the biochemical parameters demonstrated the allelopathy activity of the plant extract against the speed germination of <italic>M. pigra</italic> and <italic>V. radiata.</italic> The H<sub>2</sub>O<sub>2</sub> content of the root tissues of <italic>M. pigra</italic> and <italic>V. radiata</italic> seeds increased 4.3 and 3.8 folds, respectively, with 5% of the extract. Furthermore, the 5% extract reduced the MDA content of the non-pregerminated and pregerminated seedlings by 18% and 44%, respectively, and resulted in the inhibition of 66% and 59% in the soluble POD activities (<xref ref-type="bibr" rid="B26">Chai et&#x20;al., 2013</xref>). However, it could be interesting to investigate the effect of natural compounds isolated from <italic>E. crassipes</italic> as herbicides, since few research have been conducted. Moreover, further research is required on the physiological and ecological mechanisms of allelopathy for its worldwide application in agricultural production.</p>
</sec>
<sec id="s7-3">
<title>Insecticidal Activity</title>
<p>Few studies have demonstrated the insecticidal potential of <italic>E. crassipes</italic> extracts against household insects (<xref ref-type="bibr" rid="B53">Hassan, 2013</xref>; <xref ref-type="bibr" rid="B80">Lenora and Senthilkumar, 2017</xref>). The antifeedant potential of plant extracts at 2% varied against <italic>Tobacco caterpillar</italic>, with 57.8% in hexane extract and 35.9% in methanol extract (<xref ref-type="bibr" rid="B80">Lenora and Senthilkumar, 2017</xref>). This activity could be related to the presence of terpenoids. These results confirm the strong insecticidal activity of the plant. Future research will further explore the in-depth mechanistic effect of the plant and its bioactive compounds, to highlight its potential as natural, plant-derived pesticide for the management of plant&#x20;pests.</p>
</sec>
<sec id="s7-4">
<title>Immunostimulant Effect</title>
<p>
<italic>E. crassipes</italic> has been utilized as an immunostimulant for protection against viral, bacterial, and fungal diseases related to aquaculture. <xref ref-type="bibr" rid="B28">Chang et&#x20;al. (2013)</xref> stated that the extract of the plant, at 2 and 3&#xa0;g/kg, enhanced immune responses and resistance of prawn <italic>Macrobrachium rosenbergii</italic> against <italic>Lactococcus gravieae</italic> by 39.1% and 52.2%, respectively. Moreover, different strategies using the water extracts of <italic>E. crassipes</italic> leaves were incorporated into the diet of the prawn <italic>Macrobrachium rosenbergii</italic> as an immunostimulant against <italic>Lactococcus gravieae</italic>. As a result, the long-term administration of the infusion of the plant (2&#x2013;20&#xa0;g/kg) had increased innate immunity by 88.4% and resistance against the pathogen by 68.5% (<xref ref-type="bibr" rid="B27">Chang and Cheng, 2016</xref>). The dietary administration of <italic>E. crassipes</italic> water extract improved immunity (higher immune parameters such as LYZ, Ig, ACH50, and RBA with more than 1000 U/mL) and enhanced the resistance of rainbow trout <italic>Oncorhychus mykiss</italic> against <italic>Streptococcus iniae by</italic> 49.6% (<xref ref-type="bibr" rid="B104">Rufchaei et&#x20;al., 2020</xref>).</p>
</sec>
<sec id="s7-5">
<title>Animal Feed Formulation</title>
<p>
<italic>E. crassipes</italic> is rich in protein, vitamins, and minerals and is used as duck feed. In Indonesia, China, Philippines, and Thailand, the plant serves as a high-quality feedstock for some nonruminant animals and poultry, and in fishery. The plant biomass is also commonly used as forage for cattle, as basal feed resource or supplement to a diet consisting of sugarcane, molasses, and cereal straw, as it contains adequate minerals that are sufficient for maintenance and production requirements (<xref ref-type="bibr" rid="B55">Hossain et&#x20;al., 2015</xref>; <xref ref-type="bibr" rid="B125">Tham, 2016</xref>).</p>
</sec>
</sec>
<sec id="s8">
<title>Patents Including <italic>E. crassipes</italic> (Mart.) Solms</title>
<p>Several inventions have focused on exploring some potential ways to produce high value-added products from <italic>E. crassipes</italic> (Mart.)<italic>.</italic> Cumulative increases in the number of patents published in the last few years clearly justifies the importance of the weed in the treatment of various disorders and as a source for new therapeutic agents. As shown in <xref ref-type="table" rid="T5">Table&#x20;5</xref>, these patents have highlighted the use of the different plant parts in various applications such as antiaging, antioxidant, anti-microbial, anti-inflammatory, among others. In general, several patents found in the literature have disclosed the use of <italic>E. crassipes</italic> in the cosmetic industries, combining a traditional formula and using modern techniques of extractions to guarantee strong effects. The invention by <xref ref-type="bibr" rid="B137">Wang (2015)</xref> and <xref ref-type="bibr" rid="B30">Cui (2015)</xref> provided methods of formulation of hand and herb creams, respectively. The hand cream prepared from the plant can accelerate skin healing from secondary infection during the treatment period. The cream cooperates with the immune system to eliminate inflammation, relieve itches, and remove edema. While the herb cream is prepared by using <italic>E. crassipes</italic> with other herbal medicines through a modern technology, <xref ref-type="bibr" rid="B30">Cui (2015)</xref> has reported that the cream is suitable for preventing skin infections caused by fungi and bacteria. In addition, the invention by <xref ref-type="bibr" rid="B77">Leconte and Rossignol-Castera (2014)</xref> has described a method to prepare a novel cosmetic composition using the lipophilic extract of water hyacinth for moisturizing the skin, and to maintain and restore the hydration of the skin. Other inventions are related to the utilization of <italic>E. crassipes</italic> in medicine and pharmacology. The invention by <xref ref-type="bibr" rid="B143">Yu et&#x20;al. (2020)</xref> introduced a pharmaceutical composition for use in the treatment of inflammation. They reported that triterpenoid improves anti-inflammatory activity and antioxidant capacity, with high industrialization&#x20;value.</p>
<table-wrap id="T5" position="float">
<label>TABLE 5</label>
<caption>
<p>Patents related to <italic>E. crassipes</italic> published between 2010 and 2020.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Patent no</th>
<th align="center">Publication date</th>
<th align="center">Title</th>
<th align="center">Description of invention</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">CN104224601</td>
<td align="left">2013-03-26</td>
<td align="left">Whitening and freckle-removing sun-screening gel</td>
<td align="left">The invention relates to whitening and freckle-removing sun-screening gel using a formula of different plants including <italic>E. crassipes</italic> extractives. The whitening and freckle-removing sun-screening gel is mainly used for avoiding generating melanin, taking sun-screening, whitening, and freckle-removing effects, avoiding skin suntan and sunburn and keeping the skin young and lustrous</td>
</tr>
<tr>
<td align="left">EP2777709B1</td>
<td align="left">2014-09-17</td>
<td align="left">Use of a lipophilic extract of water hyacinth for moisturizing the skin</td>
<td align="left">A novel cosmetic composition with moisturizing effect based on a lipophilic extract to maintain and restore the hydration of the skin</td>
</tr>
<tr>
<td align="left">CN104415177A</td>
<td align="left">2015-03-18</td>
<td align="left">
<italic>E. crassipes</italic> hand cream</td>
<td align="left">The hand cream can accelerate skin healing from secondary infection during the treatment period. The cream can be easily absorbed by human bodies, cooperates with the immune system to eliminate inflammation, relieve itches, and remove edema</td>
</tr>
<tr>
<td align="left">IN3297/CHE/2013</td>
<td align="left">2015-01-30</td>
<td align="left">A novel photoprotective cinnamate from <italic>E. crassipes</italic> (Mart.) Solms used thereof as photoprotective cosmetic products</td>
<td align="left">The isolation of a novel photoprotective compound from <italic>E. crassipes</italic> and formulation of a sunscreen lotion containing the isolated compound that provides maximum ultraviolet protection ability</td>
</tr>
<tr>
<td align="left">CN104940559</td>
<td align="left">2015-09-30</td>
<td align="left">Traditional Chinese medicine external lotion for treating urticaria of children and preparation method thereof</td>
<td align="left">The invention discloses a traditional Chinese medicinal external lotion for treating urticaria of children. The traditional Chinese medicine external lotion is prepared from the raw material of <italic>E. crassipes</italic> and other herbal plants. The lotion has the efficacy of expelling wind to resolve the exterior, clearing heat and relieving itching, and has the advantages of a good curative effect, quick action, small side effects, and a low relapse rate</td>
</tr>
<tr>
<td align="left">CN104415178A</td>
<td align="left">2015-03-18</td>
<td align="left">
<italic>E. crassipes</italic> herb cream</td>
<td align="left">The herb cream is prepared by using <italic>E. crassipes</italic> with other herbal medicines through modern technology. The cream is rich in active ingredients. It is appropriate for people of all ages with high-performance penetrating agents and is externally used on skins. It is suitable for preventing skin infections caused by fungi and bacteria (gram positive)</td>
</tr>
<tr>
<td align="left">CN104414960A</td>
<td align="left">2015-03-18</td>
<td align="left">
<italic>E. crassipes</italic> conditioning cream for dermatitis</td>
<td align="left">The conditioning cream is based on <italic>E. crassipes</italic> medicines with other plants. The cream has the efficacy of clearing heat and detoxifying. The conditioning cream is capable of effectively alleviating disease. It rapidly penetrates the nidus, helps to alleviate redness, swelling, and pain, as well as local erythema, skin desquamation, and other symptoms</td>
</tr>
<tr>
<td align="left">CN105055690A</td>
<td align="left">2015-11-18</td>
<td align="left">Preparation method of water hyacinth aqueous extract and novel application of <italic>E. crassipes</italic> water extract</td>
<td align="left">The water extract at different doses (0.5&#x2013;1.5&#xa0;g&#xa0;kg<sup>&#x2212;1</sup>) demonstrated movement ability stress between mice. During a low dose of the water extract, remarkable regulating and controlling effects have been noticed with facilitation to physical ability. However, during a high dose of plant extract, remarkable regulating and controlling effect to movement velocity have been noted</td>
</tr>
<tr>
<td align="left">CN104415179A</td>
<td align="left">2015-03-18</td>
<td align="left">
<italic>E. crassipes</italic> dropping liquid for onychomycosis</td>
<td align="left">The compositions of dropping liquid from <italic>E. crassipes</italic> is effective and helps the patient to release trouble of onychomycosis</td>
</tr>
<tr>
<td align="left">CN104414899</td>
<td align="left">2015-03-18</td>
<td align="left">
<italic>E. crassipes</italic> cream for comedo and acne removal</td>
<td align="left">The cream is elaborately prepared by adopting an <italic>E. crassipes</italic> extract product, with other herbal plants through a modern technology. The plant cream has the efficacies of clearing heat, purging fire, eliminating dampness, removing blood stasis, eliminating inflammation, and preventing bacterium and can improve human body microcirculation</td>
</tr>
<tr>
<td align="left">CN104415327</td>
<td align="left">2015-03-18</td>
<td align="left">Herbal gargle containing <italic>E. crassipes</italic>
</td>
<td align="left">The herbal gargle is prepared by compounding effective components such as herbal active extracts of <italic>E. crassipes</italic>, among other herbal active extracts, with a special process. The herbal gargle is mainly used for removing oral bacteria and malodor and reducing the incidence of oral diseases. The herbal gargle has a good antibacterial effect and is suitable for all kinds of people</td>
</tr>
<tr>
<td align="left">CN104415176</td>
<td align="left">2015-03-18</td>
<td align="left">Infantile dampness transforming <italic>E. crassipes</italic> cream</td>
<td align="left">The cream is elaborately prepared by using an <italic>E. crassipes</italic> extract product as the main component through a modern technology and is suitable for conditioning maintenance of infantile eczema</td>
</tr>
<tr>
<td align="left">EP2777709A1</td>
<td align="left">2016-01-13</td>
<td align="left">Use of a lipophilic extract of <italic>E. crassipes</italic> for moisturizing the skin</td>
<td align="left">The cosmetic composition composed by the lipophilic extract maintains, or restores the hydration of the skin, with a moisturizing effect</td>
</tr>
<tr>
<td align="left">EP3068496B1</td>
<td align="left">2017-11-08</td>
<td align="left">Oily composition based on lipophilic extracts of torch ginger and <italic>E. crassipes</italic>
</td>
<td align="left">The invention relates to a novel oily composition based on lipophilic extracts of porcelain rose and to improve the radiance of the skin</td>
</tr>
<tr>
<td align="left">KR101917740B1</td>
<td align="left">2018-11-13</td>
<td align="left">Cosmetic composition containing extracts of <italic>E. crassipes</italic>
</td>
<td align="left">The cosmetic composition comprises <italic>E. crassipes</italic> extract as an active ingredient, for antioxidant, anti-inflammation, skin moisturizing, or wrinkle improvement</td>
</tr>
<tr>
<td align="left">WO2018105799A1</td>
<td align="left">2018-06-14</td>
<td align="left">Cosmetic composition containing <italic>E. crassipes</italic> extract as active ingredient</td>
<td align="left">The cosmetic composition includes <italic>E. crassipes</italic> extract as an active ingredient for antioxidant, anti-inflammatory, skin moisturizing, or anti-wrinkle properties. As a result, the skin improvement effect is excellent, particularly, wrinkle improvement</td>
</tr>
<tr>
<td align="left">CN110585879A</td>
<td align="left">2019-12-20</td>
<td align="left">Pure natural <italic>E. crassipes</italic> deodorant liquid and preparation method thereof</td>
<td align="left">Pure natural deodorant formed from <italic>E. crassipes</italic> for industrialized mass production</td>
</tr>
<tr>
<td align="left">CN107312104B</td>
<td align="left">2020-04-21</td>
<td align="left">Method for preparing alkyl polyglycoside from <italic>E. crassipes</italic> polysaccharide</td>
<td align="left">The invention adopts <italic>E. crassipes</italic> as a raw material to extract polysaccharide for the synthesis of alkyl polyglycoside with good emulsifying and foam inhibition properties</td>
</tr>
<tr>
<td align="left">CN112076237A</td>
<td align="left">2020-12-15</td>
<td align="left">Extraction process, optimization method, and application of triterpenoids in <italic>E. crassipes</italic>
</td>
<td align="left">The method takes <italic>E. crassipes</italic> as a raw material to optimize the process of triterpenoid extraction. As a result, Box&#x2013;Behnken response surface method improves the yield of triterpenoid which improves the anti-inflammatory activity and the antioxidant capacity of the extract, with high industrialization value</td>
</tr>
<tr>
<td align="left">CN111184801A</td>
<td align="left">2020-05-22</td>
<td align="left">Preparation method of <italic>E. crassipes</italic> leaf total flavonoids</td>
<td align="left">The invention relates to the extraction of total flavonoids from the leaves of the plant by adopting a homogenization&#x2013;ultrasonic method. The invention has the advantages of rapidness and high efficiency, using small amounts of the solvent with good reproducibility</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s9">
<title>Conclusion and Perspectives</title>
<p>This comprehensive review on the phytochemical composition and pharmacological/biological activities of the plant was done to assess the chemical composition and value-added applications of <italic>E. crassipes</italic> aiming to highlight the plant&#x27;s potential to enhance its limited pharmaceutical applications in Africa, especially in Ethiopia.</p>
<p>In this review, various constituents of the plant have been identified for a multitude of applications. The results of multiple phytochemical studies rely on the isolation and identification of various phytocompounds such as polyphenols, flavonoids, sterols, alkaloids, among other secondary metabolites. Phytosterols and terpenoids, considered as major compounds, could be used to provide value-added compounds for the food and pharmaceutical industries. Moreover, the physicochemical processes have been used to produce other value-added products from <italic>E. crassipes</italic> biomass, such as furfural, xylitol, enzymes, polymers, and composites and have been applied in distinct fields of applications. In this line, it will be interesting to study various strategies using combined processes for by-products production at the industrial scale. In addition, pharmacological and biological properties of <italic>E. crassipes</italic> have been discussed in detail. Different extracts and bioactive compounds isolated from the plant showed anticancer ability against various cancer cell lines. In addition, different studies witnessed the anti-inflammatory, antioxidant, antibacterial, and antifungal activities of <italic>E. crassipes</italic> extracts. Furthermore, several patents have described the pharmacological effect of the plant, but clinical applications are still rare and should be further evaluated. Since most of the studies those reported the potential effect of <italic>E. crassipes</italic> on health are animal-based studies, pharmacological findings need to be supported by the mechanisms. Other studies showed the use of <italic>E. crassipes</italic> extracts in wound healing. The plant has demonstrated potential effects in antiaging. Recent innovations targeted the development of new formulations in related fields for the standardization and validation of the plant as an antiaging agent. However, the plant requires further attention for the isolation of bioactive compounds responsible for biological activities. Accordingly, it is important to further clarify the effectiveness of compounds and elucidate their toxicity for future studies.</p>
<p>Undoubtedly, the limitations could not be avoided in this study in terms of quality and the limited number of included studies. Concurrently, new findings could increase the present therapeutic importance of <italic>E. crassipes</italic> and promote its future uses in modern medicine. Furthermore, it is necessary to investigate the pharmacological and toxicological mechanisms of the plant and establish an effective evaluation system which could promote the development and application of this valuable resource in pharmaceutical industries.</p>
</sec>
</body>
<back>
<sec id="s10">
<title>Author Contributions</title>
<p>All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. WBB collected the appropriate literature, analyzed the data, and drafted the manuscript. AE and FK provided helpful comments. MS revised the manuscript and provided helpful comments. MK, MH, LK and AY critically revised the manuscript. All authors approved the final version of the manuscript.</p>
</sec>
<sec id="s11">
<title>Funding</title>
<p>The authors are thankful to OCP and OCP Ethiopia for their assistance and financial support of this research, which is a part of the project entitled &#x201c;Integrated sustainable management of the water hyacinth in Lake Tana, Ethiopia.&#x201d;</p>
</sec>
<sec sec-type="COI-statement" id="s12">
<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 sec-type="disclaimer" id="s13">
<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>
</sec>
<sec id="s14">
<title>Supplementary Material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fphar.2022.842511/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fphar.2022.842511/full&#x23;supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="DataSheet1.PDF" id="SM1" mimetype="application/PDF" xmlns:xlink="http://www.w3.org/1999/xlink"/>
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