Antioxidant, Antimicrobial, and Anticancer Effects of Anacardium Plants: An Ethnopharmacological Perspective
- 1Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran
- 2Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Istanbul, Turkey
- 3Department of Gastronomy and Culinary Arts, School of Applied Sciences, Özyegin University, Istanbul, Turkey
- 4Bioactive Research & Innovation Food Manufac. Indust. Trade Ltd., Istanbul, Turkey
- 5Laboratory of Applied Mycology of Cariri, Department of Biological Sciences, Cariri Regional University, Crato, Brazil
- 6Laboratory of Planning and Synthesis of Drugs, Department of Antibiotics, Federal University of Pernambuco, Recife, Brazil
- 7Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato, Brazil
- 8Department of Agronomy, SAPVESA Laboratory, Nature and Life Sciences Faculty, University Chadli Bendjedid, El-Tarf, Algeria
- 9State University of Ponta Grossa, Department of Pharmaceutical Sciences, Ponta Grossa, Paraná, Brazil
- 10Department of Medical Biology, Faculty of Medicine, Nigde Ömer Halisdemir University, Campus, Nigde, Turkey
- 11Osmaniye Korkut Ata University, Bahçe Vocational School, Department of Food Processing, Osmaniye, Turkey
- 12Department of Botany, Lahore College for Women University, Lahore, Pakistan
- 13Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 14Department of Horticulture, Faculty of Agriculture, University of Khartoum, Shambat, Sudan
- 15School of Pharmacy, Kumamoto University, Kumamoto, Japan
- 16Program for Leading Graduate Schools, Health Life Science: Interdisciplinary and Glocal Oriented (HIGO) Program, Kumamoto University, Kumamoto, Japan
- 17Department of Nutrition and Dietetics, Faculty of Pharmacy, Centre for Healthy Living, University of Concepción, Concepción, Chile
- 18Unidad de Desarrollo Tecnológico, Universidad de Concepción UDT, Concepción, Chile
- 19G. B. Pant National Institute of Himalayan Environment and Sustainable Development, Garhwal Regional Centre, Uttarakhand, India
- 20Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
- 21Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal
- 22Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
Anacardium plants have received increasing recognition due to its nutritional and biological properties. A number of secondary metabolites are present in its leaves, fruits, and other parts of the plant. Among the diverse Anacardium plants' bioactive effects, their antioxidant, antimicrobial, and anticancer activities comprise those that have gained more attention. Thus, the present article aims to review the Anacardium plants' biological effects. A special emphasis is also given to their pharmacological and clinical efficacy, which may trigger further studies on their therapeutic properties with clinical trials.
Anacardium plants have received an increasing attention in recent years. Among the Anacardium plants, Anacardium occidentale (cashew apple) leaf extract is traditionally used in treating various diseases in tropical America, especially in North-Eastern Brazil. Indeed, the popular drinks in Brazil include fresh and processed cashew apple juice. Cashew plants have been used for centuries as folk medicine in South America and West Africa. Quite a number of biological properties have been reported, among them antimicrobial, antioxidant, antiulcerogenic, and anti-inflammatory effects have drawn public attention. In Nigeria, these species have also been used to treat cardiovascular disorders. While in Brazil, these species are used as infusion for curing ailments (1).
Anacardium species contain various secondary metabolites in its leaf and shoot powder, fruits and other parts of the plant, which can be used regarding their nutraceutical, medicinal and biological aspects (Table 1).
Interestingly, cashew fruit is tasty and rich in minerals, vitamins, and some essential nutrients. It has high vitamin C, nearly to five times higher than oranges and also with high minerals content. The fruit comprises of some volatile compounds, e.g., esters, terpenes, and carboxylic acids (5). Cashew bark and leaves have a rich amount of tannins (6). Cashew nut kernel testa contains tannin as an interesting economical source of antioxidants that can be used for both food and nutraceutical purposes (7). The species also contain a rich amount of flavonoids with diverse physiological effects. Anacardic acids were detected in higher amount in nutshells. Cardanol (decarboxylated anacardic acid) and cardol are found as the main components of commercial cashew nut shell liquid. Cardanol is extensively used as a synthon for the synthesis of several polymers and agricultural products (8). Cashew nut shell liquid extracted by solvent is a mixture of alkenyl phenols, including anacardic acid. As defatted, cashew kernel flour is a good source of protein and minerals. Furthermore, it can serve as low-fat fabricated food and animal feed. Animal or poultry feeds are mostly formulated using a substantial amount of cashew fiber. Besides, cashew fiber along with cashew nut shell liquid, both possess high anacardic acids contents and therefore can be utilized in functional food formulations (9).
Anacardium Plants. Key Focus on Biological Effects
Herbal treatments are the most popular form of traditional medicine and commonly used as primary health care (10). All parts of cashew tree (mainly leaf and stem bark) have been extensively used as traditional herbal medicine, contributing health benefits all over the world (Table 2) (12, 37, 38). Thus, in the last decades, Anacardium plants folk medicinal properties, and multiple biological effects being studied extensively (Tables 3, 4).
Oxidation process produces free radicals which contain unpaired electron. They can cause DNA damages and attack lipids and proteins. Antioxidants can protect free radical-induced damages by transferring electrons or hydrogen. Thus, foods with antioxidants may provide defense against free radical damage in the body and may prolong the shelf life of food products.
Fermented fruit juice of A. occidentale was reported with high antioxidant activity (140). Tan and Chan (39) reported that fresh A. occidentale leaves exhibit high antioxidant and phenolic contents as assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, potassium ferricyanide, ferric reducing antioxidant power (FRAP), ferrous ion chelating ability, ferrozine, Folin–Ciocalteu, aluminiumchloride, and molybdate assays. Cashew apple juice and pulp have been reported to have considerable amount of vitamin C (141–144). High contents of polyphenols, tannins and dietary fiber were also reported (145). Furthermore, it was reported that copper, iron, zinc, and antioxidant compounds are also present in cashew apple juice, which were more abundant compared to cashew apple fiber (146).
In vitro Studies
A. occidentale revealed high antioxidant activity through DPPH radical scavenging, ferric thiocyanate, and thiobarbituric acid assays. However, it did not exhibit nitric oxide (NO) inhibitory activity (40, 147). Good antioxidant capacity of red and yellow cashew was also observed using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and DPPH radical scavenging assays (148). Moreover, Kongkachuichai et al. (149) reported that young cashew leaves demonstrate high antioxidant capacity by oxygen radical absorbance capacity (ORAC) and FRAP assays.
Different parts of A. occidentale have strong antioxidant potency. For instance, ethanol extract of cashew nut skin demonstrated high total phenolic content and good antioxidant capacity as assessed by ABTS radical scavenging, superoxide scavenging, deoxyribose oxidation, and lipid peroxidation assays (150, 151). Andrade et al. (152) found that technical cashew nut shell liquid has high antioxidant capacity, perhaps due to its high content of cardanol and cardol, and thus it can be used as a natural antioxidant for nutraceutical and pharmaceutical purposes. The significant correlation between antioxidant capacity and the contents of anacardic acids, cardols, and cardanols was also reported, where anacardic acid content was found higher in cashew apple and fiber, whereas cardols and cardonols contents were higher in cashew nut shell liquid (9).
Antioxidant capacity of Semecarpus anacardium is also worth noting. Barman et al. (153) reported that S. anacardium nut ethanol extract had high antioxidant activity as assessed by DPPH and ABTS radical scavenging and metal chelating assays. It should be noted that antioxidant activities of plants can be affected by manufacturing process (154). Tan and Chan (39) reported that up to 30% decrease can be obtained in phenolic content and antioxidant activity of A. occidentale after blanching. However, no changes due to microwave treatment was observed. Interestingly, Trox et al. (155) reported that bioactive content of cashew nut kernels decreased after conventional shelling techniques, such as oil-bath roasting, steam roasting, drying, and open pan roasting; and they recommended flores hand-cracking method to minimize losses. Moreover, the contents of vitamin C, flavonoids, and polyphenols in cashew apple juice were increased after cold plasma treatment. Yet decreases in bioactive contents were observed at excessive exposure (156). Liao et al. (157) reported that antioxidant activity of cashew nut kernels were not affected by hot air-assisted radio frequency roasting. Moreover, sonication treatment improved the bioactive compound extraction yield from cashew apple bagasse compared to conventional heat treatment, and the optimum conditions were recommended as treatment for 6 min at an intensity of 226 W/cm2 and 1:4 bagasse-to-water ratio resulting the highest vitamin C and total phenolic contents (158). In addition, total phenolic and tannin contents of A. occidentale were increased by gamma-irradiation (159).
There are changes in the antioxidant and phenolic contents of cashew during ripening. Gordon et al. (41) observed a decrease in phenolic content of cashew apple during ripening compared unripe apple, but ascorbic acid concentration and antioxidant activity was increased during ripening. Thus, it is plausible that the antioxidant activity of cashew apple may depend on ascorbic acid rather than phenolic content (41).
The antioxidant capacity of anacardium also depends on the extraction method. Razali et al. (42) reported that A. occidentale shoots methanol extract exhibited higher antioxidant activity compared to ethyl acetate and hexane extracts as assessed by ABTS, DPPH, superoxide anion, and NO radical scavenging assays; moreover, total phenolic content of methanol extract was found to be higher. De Abreu et al. (160) reported that carotenoids content of cashew apple was higher compared to aqueous extracts. In another study, it was observed that ethyl acetate extract of S. anacardium stem bark exhibited higher phenolic content compared to that of hexane and chloroform extracts (161). Chotphruethipong et al. (162) recommended extraction at 34.7°C for 64 min with ethanol-to-solid ratio of 18:1 (v/w) as optimum conditions for cashew leaves extraction. Aqueous, ethanol and petroleum ether (60–80°C) extract from A. occidentale leaves were studied for antioxidant activities through NO production and DPPH radical assays. Ethanol extract revealed the higher potential, followed by aqueous and petroleum ether extracts (43).
The antioxidant effect of A. occidentale leaf extract was measured and exerted noticeable activity in treating RAW 264.7 macrophage cells. Leaf extract administration (0.5 and 5 μg/mL doses) reduced oxidative damage in macrophage cells. Moreover, oxidative damage attributes induced in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells was inverted by leaf extract (44). Antioxidant activity of whole cashew nuts products, treated with low- and high-temperature was also determined. Results indicated that antioxidant activities of cashew nut, kernel, and testa phenolics extracted increased with the increasing roasting temperature. The highest activity was observed in nuts roasted at 130°C for 33 min, as revealed by DPPH, ORAC, Trolox equivalent antioxidant capacity (TEAC), FRAP, and hydroxyl radical scavenging assays (163). Frozen cashew pulps from A. occidentale were investigated for antioxidant activity using FRAP and DPPH assays (164).
Methanol, hexane and ethyl acetate extracts of A. occidentale shoots were investigated through using ABTS and DPPH radicals, superoxide anion radicals, NO radicals, and ferric ions reducing assays. A. occidentale methanol extract was the most potent reducing agent and radical-scavengers. In case of ethyl acetate extract, some antioxidant effects were detected, and hexane extract was the least reactive. Methanol extract revealed 7-fold higher total phenolic content than the hexane and ethyl acetate extracts, suggesting the possible contribution of phenolics in the observed effects (42). Anacardium microcarpum antioxidant effects were also investigated on human leukocytes and erythrocytes using in vitro methods. The half maximal inhibitory concentration (IC50), for DPPH, varied from 27.9 (ethyl acetate fraction) to 32.9 μg/mL (ethanol fraction), and Fe2+ (10 μM)-induced lipid peroxidation was strongly inhibited by all fractions in rat brain and liver homogenates. Interesting, all the studied fractions were not cytotoxic to leukocytes and were able to inhibit against H2O2-induced cytotoxicity. No effects was found on human erythrocytes osmotic fragility, thus suggesting that A. microcarpum infusion can be safely consumed (1).
In vivo Studies
Technical cashew nut shell liquid decreased oxidative stress induced by paraquat or H2O2 exposure in Saccharomyces cerevisiae, demonstrating the antioxidant activity in the in vivo model assessed by DPPH scavenging and xanthine oxidase assays (152). Moreover, Encarnação et al. (15) observed antioxidant activity of A. occidentale stem bark by total phenolic content and DPPH scavenging assays, and they also reported that an oral dose of 2,000 mg/kg does not possess genotoxicity as assessed by in vivo tests on mice. Pereira et al. (165) observed antioxidant activity in rats fed with mixed tropical fruit juices containing 5% cashew apple.
The antioxidant capacity of Anacardium plants can also be related to the antimicrobial and anticancer properties. For instance, Premalatha and Sachdanandam (166) reported that S. anacardium nut extract has anticancer properties, and it was related to the high antioxidant capacity of the product, as it triggered antioxidant defense system in an in vivo study performed on male Wistar rats. The antioxidant effects of S. anacardium were also investigated by Ramprasath et al. (167) on arthritic rats. The results of this study shows that S. anacardium extract restored the increment in C-reactive protein and erythrocyte sedimentation rate observed in arthritic animals.
The ethnomedicinal use of Anacardium plants for the treatment of bacterial and fungal infections is practically limited to A. occidentale (Table 5). The applicability of this plant for these therapeutic purposes has been reported in South America, Central America, Africa, and Asia. The bark is commonly used, although the leaves, roots, seeds, and fruits also can be utilized. Despite many ethnobiological studies omitting information regarding preparation, decoction is more incidental and oral administration predominates. The species is mainly used for gastrointestinal and skin disorders, where these can be caused by action of various bacterial and fungal species. On the other side, the adaptive capacity of microorganisms has contributed to their resistance to current drugs available, with this encouraging the search for new antimicrobial substances (179).
In vitro Studies
In antibacterial property of medicinal plants from Nigeria, A. occidentale hydroethanolic extracts (leaf/bark) showed positive effects against Escherichia coli, Staphylococcus aureus, Enterobacter species, Streptococcus pneumoniae, Corynebacterium pyogenes, Enterococcus faecalis, multiresistant S. aureus, Acinetobacter species, Pseudomonas aeruginosa, and multiresistant P. aeruginosa during cavity diffusion tests with inhibition halos varying from 6 to 14 mm (18).
In the study by Akinpelu (29), A. occidentale bark methanol extract (60%) exhibited antimicrobial activity against 13 out of 15 bacterial isolates, obtaining the activity against Shigella dysenteriae and Klebsiella pneumoniae, using the agar and broth microdilution methods (20 mg/mL). In the study by Melo-Cavalcante et al. (45), the antibacterial effect of fresh (25, 50, and 100 μL/plate) and processed (100, 500, and 2,000 μL/plate) cashew juices (A. occidentale) were assessed against Salmonella typhimurium, and all tested doses revealed to be effective. Melo et al. (180) demonstrated the action of the A. occidentale stem bark hydroalcoholic extract against Streptococcus mitis, Streptococcus mutans, and Streptococcus sanguis using diffusion and microdilution techniques. The extract concentrations (50 to 0.04 mg/mL) presented halos varying from 19 to 0 mm for S. mitis, 16 to 20 mm for S. mutans and 18 to 20 mm for S. sanguis. Chlorhexidine (0.12 to 0.001875%) obtained inhibition halos of 14 to 12 mm. The bacterial surface adherence analysis revealed the extract interferes with adhesion at 0.31 and 0.15 mg/mL.
Silva et al. (181) demonstrated that methicillin resistant and sensitive S. aureus samples were sensitive to pure (100 mg/mL) and diluted (1:2-1:64) A. occidentale stem bark extract, presenting inhibition halos ranging from 10 to 20 mm. The norfloxacin control inhibition halos ranged from 11 to 36 mm.
The liquid from A. occidentale cashew bark was evaluated as a food additive for ruminants, where prior to its addition to feed, cashew nut shell liquid was tested by microdilution (0 to 50 μg/mL). The lower MIC values were obtained (1.56–6.25 μg/mL) against Ruminococcus flavefaciens, Ruminococcus albus, Ehrlichia ruminantium, and Butyrivibrio fibrisolvens and moderate values (25 to 50 μg/mL) against Streptococcus bovis and Lactobacillus ruminis. Four of the tested bacteria (Succinivibrio dextrinosolvens, Ruminobacter amylophilus, Elenomonas ruminantium, and Megasphaera elsdenii) were insensitive to cashew nut shell liquid (MIC ≥ 50 μg/mL). The bacteria Fibrobacter succinogenes, Prevotella ruminicola, and Succinimonas amylolytica were sensitive to the cashew nut shell liquid (MIC: 3.13 to 12.5 μg/mL). Thus, cashew nut shell liquid inhibits rumen-specific bacteria and its activity is promising (182).
The dried extract obtained from A. occidentale leaf powder dye (20%; 200 mg/mL) showed an effect against S. aureus which produced the largest inhibition halo (12 mm). In comparison, gentamicin and chloramphenicol produced halos of 20 and 21 mm, respectively (98).
Campos et al. (183) evaluated two A. occidentale starch (10 to 60 mg/mL) samples (crude and purified) against E. coli, S. aureus, Listeria innocua, P. aeruginosa, Enterococcus faecium, and Lactobacillus acidophilus strains. Both samples were able to inhibit growth, with MICs ranging from 20 to 30 mg/mL for the crude starch, and 40 to 60 mg/mL for the purified starch. The result was obtained for P. aeruginosa (20 mg/mL). In the subculture assay (Minimum bactericidal concentration, MBC), only the purified starch sample displayed action at 50 mg/mL. In the cell's structural analysis, changes such as pili loss and cell lysis (10 mg/mL) were observed.
Kaewpiboon et al. (184) confirmed the action of A. occidentale dry leaf ethanolic extract (5%) by disc-diffusion and microdilution, obtaining 15- and 13-mm inhibition halos and MICs of 250 and 500 μg/mL against E. coli and P. aeruginosa, respectively. Chloramphenicol (20 μg/disc) obtained a diameter varying from 15 to 30 mm and a MIC ranging from 7.1 to 125 μg/mL.
The methanolic and n-hexane extracts from A. occidentale aerial parts showed inhibitory effects against bacteria (S. aureus, E. faecalis, E. coli, P. aeruginosa, K. pneumoniae, and Mycobacterium smegmatis) with MICs ranging from 62.5 to 250 μg/mL (n-hexane) and 7.5 to >250 μg/mL (MeOH), with the effect for both extracts being obtained against S. aureus (185). A. occidentale bark ethanolic extract (3.125, 6.25, 9.375, and 12.5 mg/mL) was investigated against Streptococcus sanguinis biofilm formation. The extract inhibited biofilm formation as the concentration increased, ranging from 67.22 to 94.20%. The chlorhexidine control (0.12%) presented 89.55% inhibition (186).
An A. occidentale tincture (20%) obtained from a homeopathic Pharmacy was tested for oral bacteria biofilm-forming inhibition, and MICs of 3.12 and 0.78 mg/mL were obtained against S. mutans and Streptococcus oralis by microdilution (187). As for the diffusion, the tincture (pure 1:1) from the same Anacardium species obtained from a Manipulation Pharmacy (diluted in 20% in 70% alcohol) showed inhibition halos of 12, 13, 11, and 15 mm against S. mutans, S. salivary, E. faecalis, and Eikenella corrodens, respectively. For Chlorhexidine, the values obtained were 17, 15, 17, and 19 mm respectively (188).
Menezes et al. (78) extracted tannins from A. occidentale stem bark and evaluated by cavity diffusion its antibacterial effect against S. mutans, S. mitis, S. sanguis, Streptococcus salivarius, and Lactobacillus casei at 1:1, 1:2, to 1:16 μg/mL, with inhibition halos ranging from 11 to 17 mm. In the presence of 5% sucrose, the bacterial anti-adherence effect was observed using concentrations from 1:8 to 1:512 μg/mL, obtaining in some cases, a better effect than 0.12% chlorhexidine gluconate (1:16–1:32 μg/mL).
Fresh and processed (bleached and irradiated) leaves extracts of A. occidentale showed antibacterial effect. The minimum inhibitory doses capable of forming inhibition halos were 0.06 to 0.50 mg/disk, having an effect against Brevibacillus brevis, Micrococcus luteus, Staphylococcus cohnii, E. coli, and P. aeruginosa with the best performance being obtained for the irradiated extract (39). The A. occidentale leaf extract was investigated by Ayu et al. (189) against Aggregatibacter actinomycetemcomitans, a bacterium responsible for gingivitis. Inhibition zones ranging from 4.47 to 8.05 mm were observed for the tested concentrations (8, 41, 145, 164, 189, 190), and 96%) using agar diffusion method. The metronidazole control displayed a halo of 13.91 mm.
The cashew pulp juice extract (1 at 7.8 mg/mL) was tested against S. aureus planktonic cells and for the first time, against S. aureus biofilms where the cashew pulp juice extract was also tested in association with antimicrobials using the broth microdilution method and MBC. A MIC of 15.6 μg/mL, a MBC of 125 μg/mL and a biofilm Eradication Concentration of 500 μg/mL were obtained, demonstrating its antimicrobial and antibiofilm activity (79). The crude A. occidentale hydroalcoholic extract bark also showed good effects against S. aureus through disk diffusion (20 μL), presenting an inhibition halo of 11 mm (191).
In the study by Muraina et al. (192), A. occidentale leaf extract (10,000 μg/mL) was used against Mycoplasma spp., using the broth microdilution method. The antibiotic tylosin (1,280 μg/mL) was used as a positive control and acetone as a negative control. The authors obtained a significant result for the extract as an anti-mycoplasm product (MIC = 310 μg/mL).
Cajado et al. (193) investigated the aqueous and hydroalcoholic A. occidentale dry leaf limb extract against E. coli, S. aureus, and K. pneumoniae strains. The agar diffusion technique demonstrated S. aureus inhibition at 75 and 150 mg/mL (aqueous: 9.5 mm and hydroalcoholic: 8 and 10 mm). Moreover, amoxicillin in association with clavulanic acid (30 μg/mL) presented an action ranging from 12 to 38 mm.
Harsini (194) investigated the action of A. occidentale stem bark ethanolic extract against S. aureus by analyzing Ca2+ and K+ ion leakage inside the bacterial cell. Ca2+ leakage at 0% (control), 3, 5 and 7% concentrations varied from 2.42 to 66.73 mM, and for K+ this ranged from 15.28 to 1,251 mM, destabilizing the cell.
Quelemes et al. (195) evaluated the A. occidentale cashew starch (CG) antibacterial effect by microdilution, as well as that of its quaternized derivatives (QCG-1, QCG-2, and QCG-3) against a series of bacteria. QCG-2 and QCG-3 presented antimicrobial activity against S. aureus and Staphylococcus epidermidis (standard and resistant) where a MIC of 31.5 to 250 μg/mL and a MBC of 62.5 to 500 μg/mL were obtained. These results show the quaternized derivatives may be a promising tool in the development of biomaterials with antiseptic action.
The purified A. occidentale bark liquid was able to inhibit Bacillus subtilis growth (0.6%) and alter its morphology (0.4%). The activity of the purified cashew nut shell liquid was tested using the colony counting method, where an IC50 of 0.35% (v/v) was observed, presenting a bactericidal effect as well as cellular elongation suggesting bacterial cell division proteins may be a cashew nut shell liquid target (196).
Dos Santos et al. (197) obtained crude and fractionated extracts [hexane, dichloromethane, ethyl acetate, and methanol: ethyl acetate (9:1)] from A. occidentale leaves and evaluated these before and after being irradiated with gamma radiation, showing its effect over several S. aureus species was intensified after gamma radiation exposure (non-irradiated: MIC of 500 to >2,000 μg/mL, irradiated: MIC of 250 to >2,000 μg/mL).
De Araujo et al. (198) tested by microdilution, extracts rich in tannins obtained from A. occidentale stem bark which inhibited cariogenic bacteria growth from the Streptococcus genus, obtaining a MIC of 3,125 μg/mL (S. mitis, S. mutans) and of 6.25 μg/mL (S. oralis, S. salivarius, S. sanguinis, and Streptococcus sobrinus). The 0.12% chlorhexidine control presented MICs ranging from 0.390 to 3,125 μg/mL.
A. occidentale cashew bark oil (heated and raw-−1,600 to 0.7812 μg/mL) as well as 16 isolated compounds (anacardic acids, cardols and cardanols) were investigated by Himejima and Kubo (99). Using microdilution method, the following strains were tested: B. subtilis, Brevibacterium ammoniagenes, S. aureus, S. mutans, E. aerogenes, E. coli, P. aeruginosa, and Propionibacterium acnes. The oil's best result was obtained against B. subtilis (heated: 6.25 μg/mL and crude: 12.5 μg/mL) and S. mutans (heated: 3.13 μg/mL and crude: 3.13 μg/mL). The isolates obtained MIC values ranging from 0.39 to 100 μg/mL, with P. acnes being the most susceptible strain. Kubo et al. (199) isolated from A. occidentalis cashew, and tested through microdilution, a series of anacardic acids and (Z)-2-alkenyls against H. pylori, obtaining MIC values ranging from 200 to 800 μg/mL.
In the study by Green et al. (200), a series of anacardic acid analogs (200 μg/mL) extracted from A. occidentale with different side chains were evaluated, where phenolic, branched and alicyclic analogs were synthesized and their antibacterial activity was tested against methicillin-resistant S. aureus (MRSA) using microdilution method. The result was obtained for the side chain branched analog, 6-(40,80-dimethylnonyl) salicylic acid, and the side chain alicyclic analog, 6-cyclododecylmethyl salicylic acid (MIC = 0.39 μg/mL), respectively. This activity was greater than that of the most potent isolated antibacterial anacardic acid.
Based on the previous antibacterial anacardic acid study, 6-pentadecenyl salicylic acids isolated from A. occidentale cashew tree, a series of 6-alk(en)yl salicylic acids (200 μg/mL) were synthesized and tested for their antibacterial activity against S. mutans using broth microdilution. Among these, 6-(40,80-dimethylnonyl) salicylic acid was found to exhibit the most potent antibacterial activity against this cariogenic bacterium with a MIC of 0.78 μg/mL (201).
S. aureus and Streptococcus pyogenes were sensitive to A. occidentale cashew hexane and anacardic acid (both 20 mg/mL) extracts. When using agar diffusion, 18- and 16-mm halos were obtained for the extract and 16 mm for the acid, while microdilution analysis revealed MIC values ranged from 20 to 1:256 mg/mL. The amoxicillin control (20 mg/mL) inhibited total growth in the strains (179).
Anacardic acid (2, 10, 50, and 250 μg/mL) extracted from the cashew bark oil (A. occidentale) inhibited S. aureus biofilm formation at 40, 76, 80, and 99.96% as the concentration increased. The acid also reduced S. aureus adherence to catheters by 20% at the lowest tested dose (202). A. occidentale stem bark methanolic extract and isolated compounds (Pinostrobin, Pinocembrin, and 4-hydroxybenzaldehyde) presented inhibition zones, through disc diffusion, varying from 6.43 to 12.56 mm against Salmonella dysenteriae, Salmonella typhi, S. aureus, and E. coli, with the best results being obtained using Pinocembrin. Chloramphenicol exhibited inhibition zones of 18.71 to 21.50 mm. The IC50 varied from 62.5 to 500 (4,098 μM), with the best effect being obtained using the extract against all strains (46).
These studies using the A. occidentalis species prioritized the evaluation of hydroethanolic and methanolic extracts, using mainly the stem bark from the species. The method chosen for most of the tests was microdilution, followed by disk diffusion. Moreover, isolated compounds have already been evaluated, mostly anacardic acids. In addition to A. occidentale, two other species, A. microcarpum and Anacardium humile were tested against bacteria.
The crude ethanolic extract, ethyl acetate fraction and methanolic fraction from fresh A. microcarpum bark had their intrinsic antibacterial activity evaluated displaying antibacterial activity at 512 μg/mL (E. coli, P. aeruginosa, and S. aureus), which when combined with antibiotics, potentiated the effect of amikacin and gentamicin against the strains (134).
In another study by Barbosa-Filho et al. (1), A. microcarpum ethyl acetate fraction and methanolic fraction were tested in isolation or in combination with antibiotics (amikacin, gentamicin, ciprofloxacin, and imipenem) against E. coli, P. aeruginosa, and S. aureus. All extracts revealed low antibacterial activity against multiresistant strains (MIC = 512 μg/mL). However, the association of natural products with antibiotics presented a synergistic effect against the multiresistant E. coli strain. Moreover, the extract and ethyl acetate fraction, in conjunction with amikacin and gentamicin, also demonstrated synergism with imipenem against S. aureus.
Pereira et al. (203) evaluated three extracts (20 mg/mL) from A. humile leaves (ethanol, butanol, and hexane fractions) against S. mutans, S. aureus, and A. actinomycetemcomitans by agar diffusion and broth microdilution. Inhibition halos ranged from 9 to 19 mm, with the best result being obtained for ethanolic extract against S. aureus. MIC evaluation revealed a 0.50 mg/mL value for S. mutans, 1 mg/mL for S. aureus, and 3.50 mg/mL for A. actinomycetemcomitans. Chloramphenicol (10 μg/mL) presented halos ranging from 19 to 36 mm.
The increase in fungal resistance and the incidence of infections has led to the realization of tests aiming to evaluate the antifungal potential of species from the Anacardium genus against primary and opportunistic pathogenic fungi.
A. occidentale stem bark extract (1:1 to 1:512 mg/mL) presented action against Candida tropicalis and Candida stellatoidea strains with inhibition halos ranging from 17 to 12 and 18 to 12 mm, respectively, where the chlorhexidine gluconate control obtained halos ranging from 12 to 22 mm (204). Bahadur et al. (205) found that A. occidentale cashew bark methanol extract (150, 200, and 300 ppm) reduced conidia germination (11% at 300 ppm) of Erysiphe pisi in humid chambers for analysis under the microscope. Kolaczkowski et al. (190) assessed the A. occidentale methanol extract (aerial parts) effect against Candida glabrata, by broth microdilution, obtaining a MIC of 0.08 mg/mL, while that of the control drug fluconazole was 0.008 mg/mL.
A. occidentale burnt cashew pulp extract was evaluated against fungi from the Fusarium genus. Disc diffusion assay revealed the action of burnt cashew pulp extract (5 mg/mL) on Fusarium oxysporum (±30%), Fusarium moniliforme, and Fusarium lateritium (±60%) growth decrease. KHCO3 (20 mg/mL) control had a zone ranging from ±15% to ±28%, and the Cercobin fungicide (10 ppm) had a zone ranging from ±25 to ±30% (206).
Harsini (207) observed through colony counting that rinse solutions made from the A. occidentale bark ethanol extract (1, 2, 3, 4, and 5%) influenced C. albicans adherence to acrylic resin. The number of colonies ranged from 1757.50 to 670.00 CFU/mL, showing better results than the control (1912.50 CFU/mL).
Santos et al. (159) observed that A. occidentale leaf and bark hydroalcoholic extracts (70%) had their action improved when exposed to gamma irradiation (0, 5.0, 7.5, and 10 kGy). Disc diffusion assays showed that, against C. albicans, the extracts (2,000 μg/disc) presented halos ranging from 14 to 0 mm and from 58 to 0 mm for bark and leaves, respectively. A. occidentale tincture (200 mg/mL) obtained from a Homeopathic Pharmacy was tested by microdilution and presented action against C. albicans and Candida krusei with a MIC value of 100 mg/mL. No growth was observed with the control nystatin (100,000 IU/mL) (187). A. occidentale dried leaf ethanolic extract (20 mg/mL) was tested by Anand et al. (80) against C. albicans presenting 15.67 mm inhibition halos, with gluconate (CHX) and povidine iodine (PI) presenting 14.67 and 19.67 mm, respectively. In the microdilution assay (10,000 μg/mL), the MIC and Minimum Fungicide Concentration (MFC) of the extract obtained a value of 1,250 μg/mL (CHX-−5 μg/mL and PI-−40 and 80 μg/mL, respectively). In the biofilm assay, the density for the extract obtained was of 0.107 nm, with a potent action compared to the controls (CHX: 0.102 nm and PI: 0.186 nm).
Muzaffar et al. (139) tested anacardic acid (0 to 100 μM) against Magnaporthe oryzae. A strong conidial germination inhibition was observed by counting colony forming units in samples treated with anacardic acid (75 μM-−70%), while no inhibition was observed in the control containing dimethyl sulfoxide (DMSO-−0.1%).
Mahata et al. (208) evaluated the cardanol activity extracted from A. occidentale cashew, and its derivatives against C. albicans. The best MIC values were obtained for 4-[(4-cardanyl)azo] benzoic acid (CABA) hydrogel derivatives (8 μg/mL), followed by Self-assembled CABA (16 ug/mL) and cardanol (64 μg/mL). Drastic damages (lysis) caused by products in the fungus's membrane and cell wall were observed using scanning electron microscopy, especially by the CABA compound.
A. humile dried leaf (50 and 400 μg/mL) hydroalcoholic extract and its fractions (hexane, dichloromethane, ethyl acetate, and isobutanol) presented activity against C. albicans. Microdilution test revealed strong inhibition at 400 μg/mL for both extracts and fractions (133).
Investigations reporting the antifungal activity of Anacardium species mostly highlighted the A. occidentale species, in a similar manner to the antibacterial activity. The hydroethanolic extract was the most commonly tested extract type with the bark being the most commonly investigated plant part through microdilution and against opportunistic Candida spp. pathogens. No in vivo studies have been reported and no reports have been found against dermatophyte fungi. As observed in ethnobiological research, the medical use of this genus is the treatment of gastrointestinal symptoms and skin disorders and, therefore, studies carried out involving fungi which act with this pathogenesis profile are of extreme relevance.
Cancer is the major cause of death worldwide, researchers are working to develop more therapeutic components for cancer treatment with less side effects. Plants are the main sources of pharmacologically active molecules, used for therapeutic purposes (209–211).
Taiwo et al. (26) conducted a study with Nigerian A. occidentale leaves in cultured HeLa cells. Four isolated compounds, zoapatanolide A, agathisflavone, anacardicin, and methyl gallate, were identified, and authors found that these components exhibited HeLa cell viability reduction in dose-dependent manner, although with distinct efficiencies: zoapatanolide A > anacardicin > agathisflavone > methyl gallate. The cytotoxic potential of zoapatanolide A is well-documented in literature (212). This class of compounds act as Michael acceptor for the cysteines thiol groups, covalently modifying proteins (213, 214). Kubo et al. (215) found that the biflavonoid, agathisflavone, has antiproliferative activity against Jurkat cells (IC50 = 4.45 μM), although other compounds isolated from A. occidentale juice have also revealed cytotoxic abilities, such as anacardicin, gallic acid, and other salicylic acid derivatives. The agathisflavone effect in several cancer cell lines (colon, lung, renal, breast, and ovarian cancer) was assessed, but only a marginal activity was stated, while to the methylated derivatives promissory effects were listed against these cancer cells (216) and even against chronic myeloid leukemia cell line K562 (217). Later, the agathisflavone effect on leukemia cells growth was further studied by Konan et al. (218); this compound induced lymphopenia in vivo and selectively triggered apoptosis. In addition, it was also stated that in Jurkat cells the antiproliferative ability of agathisflavone is more effective than on acute promyeloid leukemia (APL) cell line HL60, with IC50 of 2.4 and 11.03 μg/mL, respectively. On the other hand, the identification by liquid chromatography–mass spectrometry (LC-MS) of the cashew nut shell liquid purified from Indian A. occidentale, revealed a chemical composition of cardanol, anacardic acid, and methyl cardol. It inhibited HeLa cells proliferation, triggered moderate mitotic block and HeLa cells apoptosis, besides to accelerate wound closure in L929 cells, without causing toxic effects on normal cells (196).
Kishore et al. (219) reported that anacardic acid enhance aurora kinase A activity through induction of structural changes. This compound exerted cytotoxic effects on several human cancer cell lines in vitro. In view of histone acetyltransferase (HAT) inhibition, cashew nut shell liquid, anacardic acid, and their derivatives were assessed for tumor suppressing effects. There were no-mutagenic effects up to 0.003% with and without S. typhimurium strains metabolic activation (220). Anacardic acid also inhibited cardiomyocytes hypertrophy in isolated neonatal rat in response to phenylephrine or urocortin. Anacardic acid was also as effective as Spiruchostatin A (221).
Anacardic acid-induced Aurora kinase A autophosphorylation was shown in an in silico approach, and this effects was attributed to its ability to bind and induce structural changes on the enzyme (219). Furthermore, Schultz et al. (222) stated that anacardic acid displayed effective inhibition toward estrogen receptor alpha (ERα)-expressing breast cancer cells proliferation, regardless of endocrine/tamoxifen sensitivity, while no effect was observed in ERα-negative cells. In addition, cell cycle progression inhibition and apoptosis induction in ERα -expressing cells was stated ERα-dependently. In short, as anacardic acid inhibited ERα-expressing breast cancer cells proliferation, but not the primary HuMECs, this finding reveals of utmost interest for further delineation of medical actions in cancer therapy.
Besides, marked effects were also reported by Sukumari-Ramesh et al. (223) on pituitary adenoma cells. Anacardic acid triggered polymerase cleavage induction, sub-G1 arrest, and annexin-V expression, reduced survivin and X-linked inhibitor of apoptosis protein and anti-apoptotic proteins expression, all associated with cell survival. However, carbobenzoxy-valyl-alanyl-aspartyl-(O-methyl)-fluoromethylketone failed to revert anacardic acid-induced cell death. Moreover, Chandregowda et al. (224), tested diverse benzamide derivatives synthesized for cytotoxic capacity on HeLa cells, being these compounds classified as potent as garcinol, with interesting IC50 values.
Conclusions and Future Perspectives
Anacardium plants have extensively been largely reported for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. A number of in vitro studies have been reported with promising results. On the other hand, the anticancer potential of Anacardium secondary metabolites is also quite prominent. Thus, Anacardium plants should be further studied to better elucidate their therapeutic potential not only in the in vitro and in vivo studies, but also the clinical application.
JS-R: conceptualization. JS-R, MM, AJ, WC, and NM: reviewed and editing. All authors: validation investigation, resources, data curation, writing, read and approved the final manuscript, and contributed equally to the manuscript.
Conflict of Interest
BÖ was employed by the company Bioactive Research and Innovation Food Manufac. Indust. Trade Ltd.
The remaining 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.
AJ acknowledged the funding from Uttarakhand council for Biotechnology, Pantnagar, Uttarakhand, India (File No. UCB/R&D Project/2018-311) for this work. MM would like to thank the support offered by CONICYT PIA/APOYO CCTE AFB170007.
1. Barbosa-Filho VM, Waczuk EP, Kamdem JP, Abolaji AO, Lacerda SR, Da Costa JGM, et al. Phytochemical constituents, antioxidant activity, cytotoxicity and osmotic fragility effects of Caju (Anacardium microcarpum). Indus Crops Prod. (2014) 55:280–8. doi: 10.1016/j.indcrop.2014.02.021
2. Andarwulan N, Kurniasih D, Apriady RA, Rahmat H, Roto AV, Bolling BW. Polyphenols, carotenoids, and ascorbic acid in underutilized medicinal vegetables. J Funct Foods. (2012) 4:339–47. doi: 10.1016/j.jff.2012.01.003
3. Alves AM, Dias T, Hassimotto NMA, Naves MMV. Ascorbic acid and phenolic contents, antioxidant capacity and flavonoids composition of Brazilian Savannah native fruits. Food Sci Technol. (2017) 37:564–9. doi: 10.1590/1678-457x.26716
4. Rufino MDSM, Alves RE, De Brito ES, Pérez-Jiménez J, Saura-Calixto F, Mancini-Filho J. Bioactive compounds and antioxidant capacities of 18 non-traditional tropical fruits from Brazil. Food Chem. (2010) 121:996–1002. doi: 10.1016/j.foodchem.2010.01.037
7. Viswanath V, Leo VV, Prabha SS, Prabhakumari C, Potty VP, Jisha MS. Thermal properties of tannin extracted from Anacardium occidentale L. using TGA and FT-IR spectroscopy. Nat Prod Res. (2016) 30:223–7. doi: 10.1080/14786419.2015.1040992
8. Kumar P, Paramashivappa R, Vithayathil PJ, Subba Rao PV, Srinivasa Rao A. Process for isolation of cardanol from technical cashew (Anacardium occidentale. L.) nut shell liquid. J Agric Food Chem. (2002) 50:4705–8. doi: 10.1021/jf020224w
9. Trevisan MTS, Pfundstein B, Haubner R, Würtele G, Spiegelhalder B, Bartsch H, et al. Characterization of alkyl phenols in cashew (Anacardium occidentale.) products and assay of their antioxidant capacity. Food Chem Toxicol. (2006) 44:188–97. doi: 10.1016/j.fct.2005.06.012
10. WHO. Traditional Medicine [Online]. (2018). Available online at: https://afro.who.int/health-topics/traditional-medicine (accessed).
15. Encarnação S, De Mello-Sampayo C, Graça NG, Catarino L, Da Silva IBM., Silva OMD. Total phenolic content, antioxidant activity and pre-clinical safety evaluation of an Anacardium occidentale stem bark Portuguese hypoglycemic traditional herbal preparation. Indusl Crops Prod. (2016) 82:171–8. doi: 10.1016/j.indcrop.2015.11.001
22. Olajide OA, Aderogba MA, Adedapo AD, Makinde JM. Effects of Anacardium occidentale stem bark extract on in vivo inflammatory models. J Ethnopharmacol. (2004) 95:139–42. doi: 10.1016/j.jep.2004.06.033
25. Chabi S, Adoukonou-Sagbadja H, Ahoton L, Adebo I, Adigoun F, Saidou A, et al. Indigenous knowledge and traditional management of cashew (Anacardium occidentale L.) genetic resources in Benin. JEBAS. (2013) 1:375–82.
26. Taiwo BJ, Fatokun AA, Olubiyi OO, Bamigboye-Taiwo OT, Van Heerden FR, Wright CW. Identification of compounds with cytotoxic activity from the leaf of the Nigerian medicinal plant, Anacardium occidentale L. (Anacardiaceae). Bioorg Med Chem. (2017) 25:2327–35. doi: 10.1016/j.bmc.2017.02.040
28. Nugroho A, Malik A, Pramono S. Total phenolic and flavonoid contents and in vitro anti-hypertension activity of purified extract of Indonesian cashew leaves (Anacardium occidentale L.). Int Food Res J. (2013) 20:299–305.
30. Gonçalves J, Lopes R, Oliveira D, Costa S, Miranda M, Romanos M, et al. In vitro anti-rotavirus activity of some medicinal plants used in Brazil against diarrhea. J Ethnopharmacol. (2005) 99:403–7. doi: 10.1016/j.jep.2005.01.032
32. Franca F, Cuba C, Moreira E, Miguel O, Almeida M, Das Virgens M, et al. An evaluation of the effect of a bark extracts from the cashew (Anacardium occidentale L.) on infection by Leishmania (Viannnia) brasiliensis. Rev Soc Bras Med Trop. (1993) 26:151–5. doi: 10.1590/S0037-86821993000300004
38. Brandao MG, Zanetti NN, Oliveira P, Grael CF, Santos AC, Monte-Mor RL. Brazilian medicinal plants described by 19th century European naturalists and in the Official Pharmacopoeia. J Ethnopharmacol. (2008) 120:141–8. doi: 10.1016/j.jep.2008.08.004
39. Tan YP, Chan EWC. Antioxidant, antityrosinase and antibacterial properties of fresh and processed leaves of Anacardium occidentale and Piper betle. Food Biosci. (2014) 6:17–23. doi: 10.1016/j.fbio.2014.03.001
40. Rajesh B, Potty V, Kumari P, Miranda M, Sreelekshmy S. Antioxidant and antimicrobial activity of leaves of Terminalia catappa and Anacardium occidentale: a comparative study. J Pharmacogn Phytochem. (2015) 4.
41. Gordon A, Friedrich M, Da Matta VM, Herbster Moura CF, Marx F. Changes in phenolic composition, ascorbic acid and antioxidant capacity in cashew apple (Anacardium occidentale L.) during ripening. Fruits. (2012) 67:267–76. doi: 10.1051/fruits/2012023
42. Razali N, Razab R, Junit SM, Aziz AA. Radical scavenging and reducing properties of extracts of cashew shoots (Anacardium occidentale). Food Chem. (2008) 111:38–44. doi: 10.1016/j.foodchem.2008.03.024
44. Souza NC, De Oliveira JM, Morrone MDS, Albanus RD, Amarante M, Camillo CDS, et al. Antioxidant and anti-inflammatory properties of Anacardium occidentale leaf extract. Evid Based Complement Alternat Med. (2017) 2017:2787308. doi: 10.1155/2017/2787308
45. Melo-Cavalcante AA, Rubensam G, Picada JN, Gomes Da Silva E, Fonseca Moreira JC, Henriques JP. Mutagenicity, antioxidant potential, and antimutagenic activity against hydrogen peroxide of cashew (Anacardium occidentale) apple juice and cajuina. Environ Mol Mutagen. (2003) 41:360–9. doi: 10.1002/em.10158
46. Wahyuni MMH, Yanti NA, Hartati R, Asno S, Sahidin I. Radical scavenging and antibacterial activity of phenolic compounds from Anacardium occidentale L. Stem Barks from South East Sulawesi-Indonesia. Indian J Pharm Sci. (2018) 80:143–149. doi: 10.4172/pharmaceutical-sciences.1000339
47. De Lima SG, Feitosa CM, Cito AM, Moita Neto JM, Lopes JA, Leite AS, et al. Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity. Genet Mol Res. (2008) 7:806–18. doi: 10.4238/vol7-3gmr473
50. Fazali F, Zulkhairi A, Nurhaizan M, Kamal N, Zamree M, Shahidan M. Phytochemical screening, in vitro and in vivo antioxidant activities of aqueous extract of Anacardium occidentale Linn. and its effects on endogenous antioxidant enzymes in hypercholesterolemic induced rabbits. Res J Biol Sci. (2011) 6:69–74. doi: 10.3923/rjbsci.2011.69.74
51. Amom Z, Hasan M, Baharuldin M, Abdul Kadir K, Shah Z, Kamarazaman I, et al. Assessment of antioxidative properties of aqueous leaf extract of Anacardium occidentale L. On human umbilical vein endothelial cells. Res J Med Plants. (2012) 6:597–606. doi: 10.3923/rjmp.2012.597.606
52. Lopes MMD, De Miranda MRA, Moura CFH, Eneas J. Bioactive compounds and total antioxidant capacity of cashew-apples (Anacardium occidentale L.) during the ripening of early dwarf cashew clones. Cienc E Agrotecnol. (2012) 36:325–32. doi: 10.1590/S1413-70542012000300008
53. Fidriany I, Ruslan K, Saputra J. Antioxidant activities of different polarity extracts from cashew (Anacardium occidentale L.) leaves and isolation of antioxidant compound. J Med Planta. (2013). 2.
55. Ukwenya V, Ashaolu O, Adeyemi D, Obuotor E, Tijani A, Biliaminu A, et al. Evaluation of antioxidant potential of methanolic leaf extract of Anacardium occidentale (Linn) on the testes of streptozotocin-induced diabetic wistar rats. Eur J Anat.(2013) 17:72–81.
56. Ajileye OO, Obuotor EM, Akinkunmi EO, Aderogba MA. Isolation and characterization of antioxidant and antimicrobial compounds from Anacardium occidentale L. (Anacardiaceae) leaf extract. J King Saud Univ Sci. (2015) 27:244–52. doi: 10.1016/j.jksus.2014.12.004
59. Sánchez L, Chávez J, Ríos L, Cardona S. Evaluación de un antioxidante natural extraído del marañón (Anacardium occidentale L.) para mejorar la estabilidad oxidativa del biodiesel de jatropha. Inform Tecnol. (2015) 26:19–30. doi: 10.4067/S0718-07642015000600004
60. Sija S, Potty V, Santhoshlal P. Pharmacological evaluation and detection of anacardic acid in callus culture and various plant parts of Anacardium occidentale L. Int J Pharm Sci Drug Res. (2015) 7:251–8.
61. Vasconcelos MD, Gomes-Rochette NF, De Oliveira MLM, Nunes-Pinheiro DCS, Tome AR, De Sousa FYM, et al. Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice. Exp Biol Med. (2015) 240:1648–55. doi: 10.1177/1535370215576299
62. Adeogun A, Idowu M, Ahmed S, Falomo A, Akinbile A. Kinetics, thermodynamics and antioxidant activities of water and ethanol extract of stem bark of Anacardium occidentale. Ife J Sci. (2016) 18:43–52.
63. Da Silva RA, Liberio SA, Do Amaral FMM, Do Nascimento FRF, Torres LMB, Neto VM, et al. Antimicrobial and antioxidant activity of Anacardium occidentale L. flowers in comparison to bark and leaves extracts. J Biosci Med. (2016) 4:87–9. doi: 10.4236/jbm.2016.44012
64. Nwozo S, Afolabi A, Oyinloye B. Antioxidant, lipid modulating and hypoglyceamic effects of the aqueous extract of Anacardium occidentale leave in streptozotocin-induced diabetic rats. J Mol Pathophysiol. (2016) 5:59. doi: 10.5455/jmp.20160904104639
65. Omotoso O, Adelakun S, Amedu N, Idoko U. Antioxidant properties of Moringa oleifera oil and Anacardium occidentale oil on cadmium induced liver damage in adult wistar rats. J Adv Med Pharm Sci. (2016) 7:1–7. doi: 10.9734/JAMPS/2016/24250
67. Anyaegbu O, Ajayi A, Adedapo A. Hypolipidemic and antioxidant effects of the Methanolic stem bark extract of Anacardium occidentale Linn. in triton-X 100 induced hyperlipidemic rats. Orient Pharm Exp Med. (2017) 17:211–21. doi: 10.1007/s13596-017-0262-1
68. Chooklin S, Rehbenmood K, Bunmark J, Chiangsong W. Characterization of anti-oxidative cassava starch based film supplemented with Anacardium occidentale L. leaf extract. Walailak J Sci Technol. (2017) 14:981–95.
73. Onasanwo SA, Fabiyi TD, Oluwole FS, Olaleye SB. Analgesic and anti-inflammatory properties of the leaf extracts of Anacardium occidentalis in the laboratory rodents. Niger J Physiol Sci. (2012) 27:65–71.
74. Olajide OA, Aderogba MA, Fiebich BL. Mechanisms of anti-inflammatory property of Anacardium occidentale stem bark: inhibition of NF-kappaB and MAPK signalling in the microglia. J Ethnopharmacol. (2013) 145:42–9. doi: 10.1016/j.jep.2012.10.031
75. Thomas B, Soladoye M, Adegboyega T, Agu G, Popoola O. Antibacterial and anti-inflammatory activities of Anacardium occidentale leaves and bark extracts. Nigerian J Basic Appl Sci. (2015) 23:1–6. doi: 10.4314/njbas.v23i1.1
76. Vilar MS, De Souza GL, Vilar DA, Leite JA, Raffin FN, Barbosa-Filho JM, et al. Assessment of phenolic compounds and anti-inflammatory activity of ethyl acetate phase of Anacardium occidentale L. Bark. Molecules. (2016) 21. doi: 10.3390/molecules21081087
78. Menezes K, Vieira Pereira J, De Medeiros Nóbrega D, Ramos De Freitas A, Vieira Pereira M, Vieira Pereira A. Antimicrobial and anti-adherent in vitro activity of tannins isolated from Anacardium occidentale Linn. (Cashew) on dental biolfilm bacteria. Pesquisa Bras Odontopediatr Clín Integr. (2014) 14. doi: 10.4034/PBOCI.2014.143.03
79. Dias-Souza MV, Dos Santos RM, De Siqueira EP, Ferreira-Marcal PH. Antibiofilm activity of cashew juice pulp against Staphylococcus aureus, high performance liquid chromatography/diode array detection and gas chromatography-mass spectrometry analyses, and interference on antimicrobial drugs. J Food Drug Anal. (2017) 25:589–96. doi: 10.1016/j.jfda.2016.07.009
80. Anand G, Ravinanthan M, Basaviah R, Shetty AV. In vitro antimicrobial and cytotoxic effects of Anacardium occidentale and Mangifera indica in oral care. Jo Pharm Bioallied Sci. (2015) 7:69–74. doi: 10.4103/0975-7406.148780
83. Torquato DS, Ferreira ML, Sá GC, Brito ES, Pinto GS, Azevedo EHF. Evaluation of antimicrobial activity of cashew tree gum. World J Microbiol Biotechnol. (2004) 20:505–7. doi: 10.1023/B:WIBI.0000040407.90110.c5
86. Agedah CE, Bawo DDS, Nyananyo BL. Identification of antimicrobial properties of cashew, Anacardium occidentale L. (Family Anacardiaceae). J Appl Sci Environ Manage. (2010) 14:25–7. doi: 10.4314/jasem.v14i3.61455
87. Parasa L, Sunita T, Rao K, Rao A, Rao J, Kumar L. Acetone extract of cashew (Anacardium occidentale L.) nuts shell liquid against Methicillin resistant Staphylococcus aureus (MRSA) by minimum inhibitory concentration (MIC). J Chem Pharm Res. (2011) 3:736–42.
92. Chabi SK, Sina H, Adoukonou-Sagbadja H, Ahoton LE, Roko GO, Saidou A, et al. Antimicrobial activity of Anacardium occidentale L. leaves and barks extracts on pathogenic bacteria. Afr J Microbiol Res. (2014) 8:2458–67. doi: 10.5897/AJMR2014.6859
93. Montenegro MA, Das Chagas F, Martins JL, De Vasconcelos MA, Correia VS, Soares G, et al. Effect of cashew (Anacardium occidentale L.) peduncle bagasse extract on Streptococcus mutans and its biofilm. Rev Bras Biociênc. (2014) 12:9.
95. Baby A, Nimisha B, Shehinas C, Reshna D. Comparison of antimicrobial activity of crude extracts of Mangifera indica, Psidium guajava, Piper nigrum, Anacardium occidentale and Syzygium aromaticum against dental cariogenic Streptococcus sp. Imperial J Interdiscipl Res. (2016) 2.
96. Izah S, Uhunwangho E, Dunga K, Kigigha L. Synergy of methanolic leave and stem-back extract of Anacardium occidentale L. (cashew) against some enteric and superficial bacteria pathogens. MOJ Toxicol. (2018) 4:209–11. doi: 10.15406/mojt.2018.04.00101
97. Sudjaroen Y, Thongkao K, Suwannahong K. Inappropriate of in vitro antimicrobial and anticancer activities from cashew (Anacardium occidentale L.) nut shell extracts. J Pharm Negative Results. (2018) 9:33–8. doi: 10.4103/jpnr.JPNR_6_18
98. Martínez Aguilar Y, Rodríguez FS, Saavedra MA, Hermosilla Espinosa R, Yero OM. Secondary metabolites and in vitro antibacterial activity of extracts from Anacardium occidentale L. (Cashew tree) leaves. Rev Cubana Plantas Med. (2012) 17:320–9.
103. Quelemes PV, Araruna FB, De Faria BE, Kuckelhaus SA, Da Silva DA, Mendonca RZ, et al. Development and antibacterial activity of cashew gum-based silver nanoparticles. Int J Mol Sci. (2013) 14:4969–81. doi: 10.3390/ijms14034969
104. Aderiye B, David O. In vitro antibacterial activity of aqueous extracts of cashew (Anacardium occidentale L.) fruit peels using bioautography method. Eur J Med Plants. (2014) 4:284. doi: 10.9734/EJMP/2014/6722
106. Vivek M, Manasa M, Pallavi S, Swamy H, Kumar T, Kekuda T. Antibacterial activity of Cashew (Anacardium occidentale L.) apple juice against antibiotic resistant urinary tract pathogens. World J Pharm Sci. (2014) 2:1–10. doi: 10.4314/star.v2i3.98756
107. Adesanwo J, Adewusi I, Akinpelu D, Wadim L, Mcdonald A. Phytochemical screening, antibacterial activity study and isolation of chemicals from Anacardium occidentale stem bark extract. J Pharm Res. (2016) 5:208–12.
108. Kamath K, Ramakrishna A. Comparison of antibacterial activity of leaves extracts of Tectona grandis, Mangifera indica, and Anacardium occidentale. Int J Curr Pharm Res. (2017) 9:36–9. doi: 10.22159/ijcpr.2017v9i1.16602
109. Osanaiye A, Catherine B, Anoze A. Antibacterial activity of Anacardium occidentale (cashew) leaf extracts on Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Int J Health Pharm Res. (2018) 4:19–27.
110. Tshiama C, Tshilanda D, Tshibangu D, Ngombe N, Mbemba T, Mpiana P. antidiabetic, antisickling and antibacterial activities of Anacardium occidentale L. (Anacardiaceae) and Zanthoxylum rubescens Planch. Ex Hook (Rutaceae) from DRC. Int J Diabet Endocrinol. (2018) 3:7–14. doi: 10.11648/j.ijde.20180301.12
111. Eliakim-Ikechukwu C, Obri A, Akpa O. Phytochemical and micronutrient composition of Anacardium occidentale Linn (cashew) stem-bark hydroethanolic extract and its effect on the fasting blood glucose levels and body weight of diabetic wistar rats. Int J Nutrit Wellness. (2010) 10:1–6. doi: 10.5580/6ef
112. Sambo S, Olatunde A, Luka C. Anti-diabetic activity of aqueous extract of Anacardium occidentale (Linn) stem bark in normal and alloxan-induced diabetic albino rats. J Biol Sci Bioconserv. (2014) 6:41–57.
113. Hasan MKN, Kamarazaman IS, Arapoc DJ, Taza NZM, Amom ZH, Ali RM, et al. anticholesterol activity of Anacardium occidentale Linn. Does it involve in reverse cholesterol transport? Sains Malays. (2015) 44:1501–10. doi: 10.17576/jsm-2015-4410-16
114. Konan NA, Bacchi EM, Lincopan N, Varela SD, Varanda EA. Acute, subacute toxicity and genotoxic effect of a hydroethanolic extract of the cashew (Anacardium occidentale L.). J Ethnopharmacol. (2007) 110:30–8. doi: 10.1016/j.jep.2006.08.033
115. Sokeng S, Lontsi D, Moundipa P, Jatsa H, Watcho P, Kamtchouing P. Hypoglycemic effect of Anacardium occidentale L. methanol extract and fractions on streptozotocin-induced diabetic rats. Glob J Pharmacol. (2007) 1:1–5.
116. Omoboyowa DA, Afolabi FO, Aribigbola TC. Pharmacological potential of methanol extract of Anacardium occidentale stem bark on alloxan-induced diabetic rats. Biomed Res Ther. (2018) 5:2440–54. doi: 10.15419/bmrat.v5i7.456
117. Tedong L, Dimo T, Dzeufiet P, Asongalem A, Sokeng D, Callard P, et al. Antihyperglycemic and renal protective activities of Anacardium occidentale (Anacardiaceae) leaves in streptozotocin induced diabetic rats. Afr J Trad Complement Altern Med. (2006) 3:23–35. doi: 10.4314/ajtcam.v3i1.31136
119. Ukwenya V, Ashaolu J, Adeyemi A, Akinola O, Caxton-Martins E. Antihyperglycemic activities of methanolic leaf extract of Anacardium occidentale (Linn.) on the pancreas of streptozotocin-induced diabetic rats. J Cell Anim Biol. (2012) 6:169–74. doi: 10.5897/JCAB12.028
120. Gomes CE, Cavalcante DG, Filho JE, Da Costa FN, Da Silva Pereira SL. Clinical effect of a mouthwash containing Anacardium occidentale Linn. on plaque and gingivitis control: a randomized controlled trial. Indian J Dent Res. (2016) 27:364–9. doi: 10.4103/0970-9290.191883
121. Oladele O, Ishola M. Activities of leaf extracts of cashew (Anacardium occidentale L.) and pawpaw (Carica papaya L.) against mycelia growth of Aspergillus species obtained from decayed cashew fruits. Med Plant Res. (2017) 7. doi: 10.5376/mpr.2017.07.0005
123. Laurens A, Fourneau C, Hocquemiller R, Cave A, Bories C, Loiseau PM. Antivectorial activities of cashew nut shell extracts from Anacardium occidentale L. Phytother Res. (1997) 11:145–6. doi: 10.1002/(SICI)1099-1573(199703)11:2<145::AID-PTR40>3.0.CO;2-#
124. Alvarenga TA, De Oliveira PF, De Souza JM, Tavares DC, Andrade ESML, Cunha WR, et al. Schistosomicidal activity of alkyl-phenols from the cashew Anacardium occidentale against Schistosoma mansoni adult worms. J Agric Food Chem. (2016) 64:8821–7. doi: 10.1021/acs.jafc.6b04200
125. Tripathy A, Samanta L, Das S, Parida SK, Marai N, Hazra RK, et al. The mosquitocidal activity of methanolic extracts of Lantana cramera root and Anacardium occidentale leaf: role of glutathione S-transferase in insecticide resistance. J Med Entomol. (2011) 48:291–5. doi: 10.1603/ME09122
126. Torres RC, Garbo AG, Walde RZ. Characterization and bioassay for larvicidal activity of Anacardium occidentale (cashew) shell waste fractions against dengue vector Aedes aegypti. Parasitol Res. (2015) 114:3699–702. doi: 10.1007/s00436-015-4598-5
127. Torres R, Garbo A, Walde R. Larvicidal and ovicidal activities, characterization and stability of Anacardium occidentale (Cashew) shell wastes. Virol Res Rev. (2017) 1:1–3. doi: 10.15761/VRR.1000129
128. Da Costa CDE, Herculano EA, Silva JCG, Paulino ET, Bernardino AC, Araujo JX, et al. Hypotensive, vasorelaxant and antihypertensive activities of the hexane extract of Anacardium occidentale Linn. Arch Biol Sci. (2018) 70:459–68. doi: 10.2298/ABS171109006C
129. Panjwani D, Purohit V, Siddiqui H. Antidepressant-like effects of Anacardium occidentale L. leaves in the mouse forced swim and tail suspension tests. Pharmacologia. (2015) 6:186–91. doi: 10.5567/pharmacologia.2015.186.191
131. Kamath K, Shabaraya A, Azharuddin M, Gopikrishna K, Srinivas U. Anthelmintic activity of leaves extracts of Anacardium Occidentale and Mangifera Indica (anacardiaceae). Am J Pharmtech Res. (2003) 3:560–4.
132. Porto R, Fett R, Areas J, Brandao A, Morgano M, Soares R, et al. Bioactive compounds, antioxidant activity and minerals of Caju (Anacardium humile St. Hill) during the ripening. Afr J Agric Res. (2016) 11:4924–30. doi: 10.5897/AJAR2016.11455
133. Royo VA, Mercadante-Simoes MO, Ribeiro LM, Oliveira DA, Aguiar MM, Costa ER, et al. Anatomy, histochemistry, and antifungal activity of Anacardium humile (Anacardiaceae) leaf. Microsc Microanal. (2015) 21:1549–61. doi: 10.1017/S1431927615015457
134. Barbosa-Filho VM, Waczuk EP, Leite NF, Menezes IR, Da Costa JG, Lacerda SR, et al. Phytocompounds and modulatory effects of Anacardium microcarpum (cajui) on antibiotic drugs used in clinical infections. Drug Des Devel Ther. (2015) 9:5965–72. doi: 10.2147/DDDT.S93145
135. Celis C, García A, Sequeda G, Mendez G, Torrenegra R. Antimicrobial activity of extracts obtained from Anacardium excelsum againts some pathogenic microorganisms. Emirates J Food Agric. (2011) 249–57.
137. Curado F, Gazolla A, Pedroso R, Pimenta L, De Oliveira P, Tavares D, et al. Antifungal and cytotoxicity activities of Anacardium othonianum extract. J Med Plants Res. (2016) 10:450–6. doi: 10.5897/JMPR2016.6115
138. Melo-Cavalcante A, Picada J, Rubensam G, Henriques J. Antimutagenic activity of cashew apple (Anacardium occidentale Sapindales, Anacardiaceae) fresh juice and processed juice (cajuína) against methyl methanesulfonate, 4-nitroquinoline N-oxide and benzo [a] pyrene. Genet Mol Biol. (2008) 31:759–66. doi: 10.1590/S1415-47572008000400024
139. Muzaffar S, Bose C, Banerji A, Nair BG, Chattoo BB. Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae. Appl Microbiol Biotechnol. (2016) 100:323–35. doi: 10.1007/s00253-015-6915-4
142. Assunção RB, Mercadante AZ. Carotenoids and ascorbic acid composition from commercial products of cashew apple (Anacardium occidentale L.). J Food Compos Anal. (2003) 16:647–57. doi: 10.1016/S0889-1575(03)00098-X
143. Eça KS, Machado MTC, Hubinger MD, Menegalli FC. Development of active films from pectin and fruit extracts: light protection, antioxidant capacity, and compounds stability. J Food Sci. (2015) 80:C2389–96. doi: 10.1111/1750-3841.13074
145. Maria Do Socorro MR, Pérez-Jiménez J, Tabernero M, Alves RE, De Brito ES, Saura-Calixto F. Acerola and cashew apple as sources of antioxidants and dietary fibre. Int J Food Sci Technol. (2010) 45:2227–33. doi: 10.1111/j.1365-2621.2010.02394.x
146. De Lima ACS, Soares DJ, Da Silva LMR, De Figueiredo RW, De Sousa PHM, Menezes ED. In vitro bioaccessibility of copper, iron, zinc and antioxidant compounds of whole cashew apple juice and cashew apple fibre (Anacardium occidentale L.) following simulated gastro-intestinal digestion. Food Chem. (2014) 161:42–7. doi: 10.1016/j.foodchem.2014.03.123
147. Abas F, Lajis NH, Israf DA, Khozirah S, Umi Kalsom Y. Antioxidant and nitric oxide inhibition activities of selected Malay traditional vegetables. Food Chem. (2006) 95:566–73. doi: 10.1016/j.foodchem.2005.01.034
148. Moo-Huchin VM, Moo-Huchin MI, Estrada-León RJ, Cuevas-Glory L, Estrada-Mota IA, Ortiz-Vázquez E, et al. Antioxidant compounds, antioxidant activity and phenolic content in peel from three tropical fruits from Yucatan, Mexico. Food Chem. (2015) 166:17–22. doi: 10.1016/j.foodchem.2014.05.127
149. Kongkachuichai R, Charoensiri R, Yakoh K, Kringkasemsee A, Insung P. Nutrients value and antioxidant content of indigenous vegetables from Southern Thailand. Food Chem. (2015) 173:838–46. doi: 10.1016/j.foodchem.2014.10.123
151. Rajini PS. Cashew nut (Anacardium occidentale l.) skin extract as a free radical scavenger. In: Preedy VR, Watson RR, Patel VB, editors. Nuts and Seeds in Health and Disease Prevention. San Diego, CA: Academic Press (2011). p. 301–8.
152. Andrade TDJDS, Araújo BQ, Citó AMDGL, Da Silva J, Saffi J, Richter, et al. Antioxidant properties and chemical composition of technical cashew nut shell liquid (tCNSL). Food Chem. (2011) 126:1044–8. doi: 10.1016/j.foodchem.2010.11.122
154. Queiroz C, Lopes MLM, Fialho E, Valente-Mesquita VL. Changes in bioactive compounds and antioxidant capacity of fresh-cut cashew apple. Food Res Int. (2011) 44:1459–62. doi: 10.1016/j.foodres.2011.03.021
155. Trox J, Vadivel V, Vetter W, Stuetz W, Scherbaum V, Gola U, et al. Bioactive compounds in cashew nut (Anacardium occidentale L.) kernels: effect of different shelling methods. J Agric Food Chem. (2010) 58:5341–6. doi: 10.1021/jf904580k
156. Rodríguez Ó, Gomes WF, Rodrigues S, Fernandes FN. Effect of indirect cold plasma treatment on cashew apple juice (Anacardium occidentale L.). LWT Food Sci Technol. (2017) 84:457–63. doi: 10.1016/j.lwt.2017.06.010
157. Liao M, Zhao Y, Gong C, Zhang H, Jiao S. Effects of hot air-assisted radio frequency roasting on quality and antioxidant activity of cashew nut kernels. LWT Food Sci Technol. (2018) 93:274–80. doi: 10.1016/j.lwt.2018.03.047
158. Fonteles TV, Leite AKF, Da Silva ARA, Fernandes FN, Rodrigues S. Sonication effect on bioactive compounds of cashew apple bagasse. Food Bioprocess Technol. (2017) 10:1854–64. doi: 10.1007/s11947-017-1960-x
159. Santos G, Silva E, Silva B, Sena K, Lima C. Influence of gamma radiation on the antimicrobial activity of crude extracts of Anacardium occidentale L., Anacardiaceae, rich in tannins. Rev Bras Farmacogn. (2011) 21:444–9. doi: 10.1590/S0102-695X2011005000045
160. De Abreu FP, Dornier M, Dionisio AP, Carail M, Caris-Veyrat C, Dhuique-Mayer C. Cashew apple (Anacardium occidentale L.) extract from by-product of juice processing: a focus on carotenoids. Food Chem. (2013) 138:25–31. doi: 10.1016/j.foodchem.2012.10.028
162. Chotphruethipong L, Benjakul S, Kijroongrojana K. Optimization of extraction of antioxidative phenolic compounds from cashew (Anacardium occidentale L.) leaves using response surface methodology. J Food Biochem. (2017) 41:e12379. doi: 10.1111/jfbc.12379
163. Chandrasekara N, Shahidi F. Effect of roasting on phenolic content and antioxidant activities of whole cashew nuts, kernels, and testa. J Agric Food Chem. (2011) 59:5006–14. doi: 10.1021/jf2000772
164. Zielinski A, Avila S, Ito V, Nogueira A, Wosiacki G, Haminiuk C. The association between chromaticity, phenolics, carotenoids, and in vitro antioxidant activity of frozen fruit pulp in Brazil: an application of chemometrics. J Food Sci. (2014) 79:C510–6. doi: 10.1111/1750-3841.12389
165. Pereira ACDS, Dionísio AP, Wurlitzer NJ, Alves RE, Brito ESD, Silva AMDOE, et al. Effect of antioxidant potential of tropical fruit juices on antioxidant enzyme profiles and lipid peroxidation in rats. Food Chem. (2014) 157:179–85. doi: 10.1016/j.foodchem.2014.01.090
166. Premalatha B, Sachdanandam P. Semecarpus anacardium L. nut extract administration induces the in vivo antioxidant defence system in aflatoxin B1 mediated hepatocellular carcinoma. J Ethnopharmacol. (1999) 66:131–9. doi: 10.1016/S0378-8741(99)00029-X
167. Ramprasath VR, Shanthi P, Sachdanandam P. Evaluation of antioxidant effect of Semecarpus anacardium Linn. nut extract on the components of immune system in adjuvant arthritis. Vasc Pharmacol. (2005) 42:179–86. doi: 10.1016/j.vph.2005.02.001
168. Costa I, Bonfim F, Pasa M, Montero D. Ethnobotanical survey of medicinal flora in the rural community Rio dos Couros, state of Mato Grosso, Brazil. Bol Latinoamericano Caribe Plant Med Aromáticas. (2017) 16:53–67.
169. Vieira D, Amaral F, Maciel M, Nascimento F, Libério S, Rodrigues V. Plant species used in dental diseases:ethnopharmacology aspects and antimicrobial activity evaluation. J Ethnopharmacol. (2014) 155:1441–9. doi: 10.1016/j.jep.2014.07.021
170. Souza C, Brandão D, Silva M, Palmeira A, Simões M, Medeiros A. Use of medicinal plants with antimicrobial activity by users of the Public Health System in Campina Grande-Paraíba, Brazil. Rev Bras Plant Med. (2013) 15:188–93. doi: 10.1590/S1516-05722013000200004
171. De Carvalho Nilo Bitu V, De Carvalho Nilo Bitu V, Matias EF, De Lima WP, Da Costa Portelo A, Coutinho HD, et al. Ethnopharmacological study of plants sold for therapeutic purposes in public markets in Northeast Brazil. J Ethnopharmacol. (2015) 172:265–72. doi: 10.1016/j.jep.2015.06.022
172. Mustapha A. Ethnobotanical field survey of medicinal plants used by traditional medicine practitioners to manage HIV/AIDS opportunistic infections and their prophylaxis in Keffi Metropolis, Nigeria. Asian J Plant Sci Res. (2014) 4:7–14.
173. Randriamiharisoa MN, Kuhlman AR, Jeannoda V, Rabarison H, Rakotoarivelo N, Randrianarivony T, et al. Medicinal plants sold in the markets of Antananarivo, Madagascar. J Ethnobiol Ethnomed. (2015) 11:60. doi: 10.1186/s13002-015-0046-y
174. Yabesh J, Prabhu S, Vijayakumar S. An ethnobotanical study of medicinal plants used by traditional healers in silent valley of Kerala, India. J Ethnopharmacol. (2014) 154:774–89. doi: 10.1016/j.jep.2014.05.004
177. Kankara S, Ibrahim M, Mustafa M, Go R. Ethnobotanical survey of medicinal plants used for traditional maternal healthcare in Katsina state, Nigeria. South Afr J Bot. (2015) 97:165–75. doi: 10.1016/j.sajb.2015.01.007
178. Mata N, De Sousa R, Perazzo F, Carvalho J. The participation of Wajãpi women from the State of Amapá (Brazil) in the traditional use of medicinal plants–a case study. J Ethnobiol Ethnomed. (2012) 8:48. doi: 10.1186/1746-4269-8-48
179. Monteiro AS, Rodrigues RCE, Da Silva GF, Albuquerque PM. Estudo da actividade antimicrobiana da casa da castanha de caju (Anacardium occidentale). J Eng Exact Sci. (2017) 3:705–10. doi: 10.18540/24469416030420170705
180. Melo AFM, Santos EJV, Souza LFC, Carvalho AT, Pereira MSV, Higino JS. Atividade antimicrobiana in vitro do extrato de Anacardium occidentale L. sobre espécies de Streptococcus. Braz J Pharmacogn. (2006) 16:202–5. doi: 10.1590/S0102-695X2006000200012
181. Silva JGD, Souza IA, Higino JS, Siqueira-Junior JP, Pereira JV, Pereira MDSV. Atividade antimicrobiana do extrato de Anacardium occidentale Linn. em amostras multiresistentes de Staphylococcus aureus. Rev Bras Farmacogn. (2007) 17:572–7. doi: 10.1590/S0102-695X2007000400016
182. Watanabe Y, Suzuki R, Koike S, Nagashima K, Mochizuki M, Forster RJ, et al. In vitro evaluation of cashew nut shell liquid as a methane-inhibiting and propionate-enhancing agent for ruminants. J Dairy Sci. (2010) 93:5258–67. doi: 10.3168/jds.2009-2754
183. Campos DA, Ribeiro AC, Costa EM, Fernandes JC, Tavaria FK, Araruna FB, et al. Study of antimicrobial activity and atomic force microscopy imaging of the action mechanism of cashew tree gum. Carbohydr Polym. (2012) 90:270–4. doi: 10.1016/j.carbpol.2012.05.034
184. Kaewpiboon C, Lirdprapamongkol K, Srisomsap C, Winayanuwattikun P, Yongvanich T, Puwaprisirisan P, et al. Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities of selected Thai medicinal plants. BMC Complement Altern Med. (2012) 12:217. doi: 10.1186/1472-6882-12-217
185. Madureira A, Ramalhete C, Mulhovo S, Duarte A, Ferreira M. Antibacterial activity of some African medicinal plants used traditionally against infectious diseases. Pharm Biol. (2012) 50:481–9. doi: 10.3109/13880209.2011.615841
186. Amaliah R, Larnani S, Wahyudi I. Inhibition effect of cashew stem bark extract (Anacardium occidentale L.) on biofilm formation of Streptococcus sanguinis. Dent J Majalah Kedokteran Gigi. (2012) 45:212–6. doi: 10.20473/j.djmkg.v45.i4.p212-216
188. Ferreira Filho J, Gondim B, Da Cunha D, De Figueiredo C, Valença A. Physical properties and antibacterial activity of herbal tinctures of Calendula (Calendula officinalis L.) and Cashew Tree (Anacardium occidentale L.). Pesquisa Bras Odontopediatr Clin Integr. (2014) 14:49–53.
189. Ayu N, Indraswary R, Christiono S. Efektivitas ekstrak daun jambu mete (Anacardium occidentale L) terahdap pertumbuhan Aggregatibacter actinomycetemcomitans pada gingivitis-in vitro. Odonto Dent J. (2014) 1:44–8. doi: 10.30659/odj.1.1.44-48
190. Kolaczkowski M, Kolaczkowska A, Sroda K, Ramalhete C, Michalak K, Mulhovo S, et al. Substrates and modulators of the multidrug transporter Cdr1p of Candida albicans in antifungal extracts of medicinal plants. Mycoses. (2010) 53:305–10. doi: 10.1111/j.1439-0507.2009.01711.x
192. Muraina I, Adaudi A, Mamman M, Kazeem H, Picard J, Mcgaw L, et al. Antimycoplasmal activity of some plant species from northern Nigeria compared to the currently used therapeutic agent. Pharm Biol. (2010) 48:1103–7. doi: 10.3109/13880200903505633
193. Cajado A, Aragão P, Oliveira M. Efeito antimicrobiano in vitro do extrato aquoso e hidroalcoólico das folhas de Anacardium ocidentale e Mangifera indica. J Health Sci. (2016) 18:177–82. doi: 10.17921/2447-8938.2016v18n3p177-82
194. Harsini H. Aktivitas antibakteri ekstrak etanolik kulit batang jambu mete (Anacardium occidentale Linn.) terhadap Staphylococcus aureus. Majalah Kedokteran Gigi Indonesia. (2017) 3:10–4. doi: 10.22146/majkedgiind.17498
195. Quelemes P, De Araújo A, Plácido A, Delerue-Matos C, Maciel J, Bessa L, et al. Quaternized cashew gum: an anti-staphylococcal and biocompatible cationic polymer for biotechnological applications. Carbohydr Polym. (2017) 157:567–75. doi: 10.1016/j.carbpol.2016.10.026
196. Ashraf M, Rathinasamy K. Antibacterial and anticancer activity of the purified cashew nut shell liquid: implications in cancer chemotherapy and wound healing. Nat Prod Res. (2018) 32:2856–60. doi: 10.1080/14786419.2017.1380022
197. Dos Santos GHF, Amaral A, Da Silva EB. Antibacterial activity of irradiated extracts of Anacardium occidentale L. on multiresistant strains of Staphylococcus aureus. Appl Radiat Isotopes. (2018) 140:327–32. doi: 10.1016/j.apradiso.2018.07.035
198. De Araujo JSC, De Castilho ARF, Lira AB, Pereira AV, De Azevedo TKB, De Brito Costa EMM, et al. Antibacterial activity against cariogenic bacteria and cytotoxic and genotoxic potential of Anacardium occidentale L. and Anadenanthera macrocarpa (Benth) Brenan extracts. Arch Oral Biol. (2018) 85:113–9. doi: 10.1016/j.archoralbio.2017.10.008
202. Sajeevan SE, Chatterjee M, Paul V, Baranwal G, Kumar VA, Bose C, et al. Impregnation of catheters with anacardic acid from cashew nut shell prevents Staphylococcus aureus biofilm development. J Appl Microbiol. (2018) 125:1286–95. doi: 10.1111/jam.14040
203. Pereira EM, Gomes RT, Freire NR, Aguiar EG, Brandao M, Santos VR. In vitro antimicrobial activity of Brazilian medicinal plant extracts against pathogenic microorganisms of interest to dentistry. Planta Med. (2011) 77:401–4. doi: 10.1055/s-0030-1250354
204. Araújo C, Pereira M, Higino J, Pereira J, Martins A. Atividade antifúngica in vitro da casca do Anacardium occidentale linn. sobre leveduras do gênero candida. Arq Cent Estud Curso Odontol Univ Fed Minas Gerais. (2005) 41:263–70.
205. Bahadur A, Singh UP, Singh DP, Sarma BK, Singh KP, Singh A, et al. Control of Erysiphe pisi causing powdery mildew of pea (Pisum sativum) by cashewnut (Anacardium occidentale) shell extract. Mycobiology. (2008) 36:60–5. doi: 10.4489/MYCO.2008.36.1.060
206. Santos R, Sá R, Marinho M, Martins J, Teixeira E, Alves F, et al. Compositional analysis of cashew (Anacardium occidentale L.) peduncle bagasse ash and its in vitro antifungal activity against Fusarium species. Rev Bras Biociênc. (2011) 9.
207. Harsini H. Pengaruh Ekstrak Etanolik Kulit Batang Jambu Mete (Anacardium occidentale Linn) sebagai Bahan Kumur terhadap Daya Perlekatan C. albicans pada Plat Resin Akrilik. Majalah Kedokteran Gigi Indonesia. (2016) 18:137–40. doi: 10.22146/majkedgiind.15398
208. Mahata D, Mandal SM, Bharti R, Gupta VK, Mandal M, Nag A, et al. Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability. Int J Biol Macromol. (2014) 69:5–11. doi: 10.1016/j.ijbiomac.2014.05.017
209. Iacopetta D, Grande F, Caruso A, Mordocco RA, Plutino MR, Scrivano L, et al. New insights for the use of quercetin analogs in cancer treatment. Future Med Chem. (2017) 9:2011–28. doi: 10.4155/fmc-2017-0118
210. Fazio A, Iacopetta D, La Torre C, Ceramella J, Muia N, Catalano A, et al. Finding solutions for agricultural wastes: antioxidant and antitumor properties of pomegranate Akko peel extracts and beta-glucan recovery. Food Funct. (2018) 9:6618–31. doi: 10.1039/C8FO01394B
211. Ceramella J, Loizzo MR, Iacopetta D, Bonesi M, Sicari V, Pellicano TM, et al. Anchusa azurea Mill. (Boraginaceae) aerial parts methanol extract interfering with cytoskeleton organization induces programmed cancer cells death. Food Funct. (2019) 10:4280–90. doi: 10.1039/C9FO00582J
213. Zhang S, Won YK, Ong CN, Shen HM. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. (2005) 5:239–49. doi: 10.2174/1568011053765976
214. Scotti MT, Fernandes MB, Ferreira MJP, Emerenciano VP. Quantitative structure-activity relationship of sesquiterpene lactones with cytotoxic activity. Bioorg Med Chem. (2007) 15:2927–34. doi: 10.1016/j.bmc.2007.02.005
216. De Souza J, Fernandes C, Grivicich I, Brondani A, De Carvalho MG. Antitumor activity of biflavonoids from Ouratea and Luxemburgia on human cancer cell lines. Indian J Pharmacol. (2007) 39:184–6. doi: 10.4103/0253-7613.36536
217. Grynberg NF, Carvalho MG, Velandia JR, Oliveira MC, Moreira IC, Braz-Filho R, et al. DNA topoisomerase inhibitors: biflavonoids from Ouratea species. Braz J Med Biol Res. (2002) 35:819–22. doi: 10.1590/S0100-879X2002000700009
218. Konan NA, Lincopan N, Collantes Díaz IE, De Fátima Jacysyn J, Tanae Tiba MM, Pessini Amarante Mendes JG, et al. Cytotoxicity of cashew flavonoids towards malignant cell lines. Exp Toxicol Pathol. (2012) 64:435–40. doi: 10.1016/j.etp.2010.10.010
219. Kishore H, Vedamurthy B, Mantelingu K, Agrawal S, Ashok R, Roy S. Kundu specific small-molecule activator of aurora kinase a induces autophosphorylation in a cell-free system. J Med Chem. (2008) 51:792–7. doi: 10.1021/jm700954w
221. Davidson SM, Townsend PA, Carroll C, Yurek-George A, Balasubramanyam K, Kundu TK, et al. The transcriptional coactivator p300 plays a critical role in the hypertrophic and protective pathways induced by phenylephrine in cardiac cells but is specific to the hypertrophic effect of urocortin. Chembiochem. (2005) 6:162–70. doi: 10.1002/cbic.200400246
222. Schultz DJ, Wickramasinghe NS, Ivanova MM, Isaacs SM, Dougherty SM, Imbert-Fernandez Y, et al. Anacardic acid inhibits estrogen receptor alpha-DNA binding and reduces target gene transcription and breast cancer cell proliferation. Mol Cancer Ther. (2010) 9:594–605. doi: 10.1158/1535-7163.MCT-09-0978
223. Sukumari-Ramesh S, Singh N, Jensen M, Dhandapani K, Vender J. Anacardic acid induces caspase-independent apoptosis and radiosensitizes pituitary adenoma cells laboratory investigation. J Neurosurg. (2011) 114:1681–90. doi: 10.3171/2010.12.JNS10588
Keywords: Anacardium, cashew nut, phytotherapy, antioxidant, antimicrobial, anticancer
Citation: Salehi B, Gültekin-Özgüven M, Kirkin C, Özçelik B, Morais-Braga MFB, Carneiro JNP, Bezerra CF, Silva TG, Coutinho HDM, Amina B, Armstrong L, Selamoglu Z, Sevindik M, Yousaf Z, Sharifi-Rad J, Muddathir AM, Devkota HP, Martorell M, Jugran AK, Cho WC and Martins N (2020) Antioxidant, Antimicrobial, and Anticancer Effects of Anacardium Plants: An Ethnopharmacological Perspective. Front. Endocrinol. 11:295. doi: 10.3389/fendo.2020.00295
Received: 24 February 2020; Accepted: 20 April 2020;
Published: 12 June 2020.
Edited by:Wen Zhou, Case Western Reserve University, United States
Reviewed by:Domenico Iacopetta, University of Calabria, Italy
Giovanni Luca, University of Perugia, Italy
Copyright © 2020 Salehi, Gültekin-Özgüven, Kirkin, Özçelik, Morais-Braga, Carneiro, Bezerra, Silva, Coutinho, Amina, Armstrong, Selamoglu, Sevindik, Yousaf, Sharifi-Rad, Muddathir, Devkota, Martorell, Jugran, Cho and Martins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Javad Sharifi-Rad, email@example.com; Miquel Martorell, firstname.lastname@example.org; Arun Kumar Jugran, email@example.com; William C. Cho, firstname.lastname@example.org; Natália Martins, email@example.com