Anacardic Acid Research Articles

Profile of phenolic compounds and antimicrobial potential of hydroalcoholic extracts from cashew-apple coproducts

Phytochemicals from tropical fruits and their by-products have shown the potential to use as antimicrobial natural. This study aimed to optimize the recovery of phenolic compounds (total polyphenols and flavonoids) from cashew apple using ultrasound-assisted extraction to promote the functional attributes to its coproducts and to evaluate their antioxidant and antimicrobial potential. An experimental design applying a response surface methodology was used for the extraction process. The ethanol concentration (13.76 % to 56.21 %) and the ultrasonic bath time (21.71 to 78.28 min.) were considered as independent variables, and the polyphenols content, total flavonoids as dependent variables. The phenolic profile of optimized hydroalcoholic extracts (UPLC-QToF-MSE) and their antimicrobial potential against foodborne pathogenic bacteria was assessed. The optimized conditions for a total phenolic extract of 750 mg GAE 100 g-1 were 42.16 % ethanol and 37.34 min in an ultrasonic bath, and for total flavonoids of 479.07 mg of quercetin per 100 g-1 were 37.15 % ethanol and 25.13 min. A total of 15 compounds including quercetin and myricetin derivatives, gallic acid, and anacardic acid were identified. The extracts displayed effective action against Staphylococcus aureus and Listeria monocytogenes. The extracts were effective against foodborne pathogenic bacteria thus demonstrating their potential to be a good natural alternative to synthetic additives in the food industry.

Development of anacardic acid-loaded zein nanoparticles: Physical chemical characterization, stability and antimicrobial improvement

Anacardic acid (AA) has gained interest regarding its extraordinary antimicrobial activity. Nanotechnology based delivery systems are a modern approach to improve both pharmacological and functional properties of therapeutic agents. In this paper we aimed to design and characterize AA loaded-zein nanoparticles and evaluate its antimicrobial efficiency in vitro using microdilution and antibiofilm assays. AA nanoparticles were spherical, stable, with an average size of 381.6 nm and negative ζ potential. The saturation transfer difference-NMR analysis demonstrated the association of zein and AA in two different conformations, enlightening its enhanced pharmacological activity. Bacteriostatic concentrations were 0.05 and 3.12 μg/ml for Staphylococcus aureus and Pseudomonas aeruginosa, while bactericide activity was observed only for S. aureus at 0.2 μg/ml. Fungistatic/fungicide concentrations for Candida rugosa were 1.17/2.34 μg/ml, for Candida albicans and Candida parapsilosis 2.34/4.69 μg/ml and for Candida tropicalis, Candida jardinii, Candida glabratta and Candida auris 4.69/4.69 μg/ml. Furthermore, nanoencapsulated AA was more efficient in reducing S. aureus and C. albicans biofilms viability than AA solution, while they presented a similar inhibition against P. aeruginosa biofilm. Therefore, AA loaded-zein nanoparticles could represent an alternative for potential applications where the low concentrations of this phytochemical are useful to prevent or treat bacterial and fungical infections.

Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases

BackgroundIn the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds.ResultsWe herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations.ConclusionsOur finding provides two novel natural products as promising SARS-CoV-2 antivirals.

In vitro antileishmanial activity of Anacardium othonianum and isolated compounds against Leishmania amazonensis

This study analyzes the antileishmanial activity of the crude ethanol extract, fractions, and isolated compounds of A. othonianum nuts. Antileishmanial activity was evaluated against Leishmania amazonensis promastigotes in vitro. The phytochemical study was performed by high-performance liquid chromatography-high-resolution mass spectrometry-diode array detector (HPLC-HRMS-DAD) and by preparative HPLC. HPLC-HRMS-DAD analysis of the bioactive extract confirmed the presence of ten alkyl phenol derivatives that had previously been isolated from A. occidentale. Bioassay-guided isolation afforded cardanol triene, cardanol diene, cardanol monoene, cardol triene, anacardic acid triene, anacardic acid diene, and anacardic acid monoene. Cardol triene gave an IC50 of 80.66 µM. The obtained data suggest that the evaluated extract, fractions, and cardol triene had moderate activity against L. amazonensis promastigotes. This is the first description of alkyl phenols in A. othonianum.

Anacardic Acid: A Promising Building Block for the Sustainable Preparation of Vesicular Nanosystems

Anacardic acid is a renewable product extracted, under mild conditions, from the cashew nuts. Its importance is growing with time thanks to various high-value biotechnological applications. In this research, anacardic acid has been used both in pristine form, and as the main component combined with cholesterol, to prepare three different nanoformulations through an environmentally friendly procedure. Physicochemical characterization shown stable and well-shaped spherical nanomorphologies with a mean diameter of about 220 nm. Stability studies in aqueous solution involving different anacardic acid-based formulations at different temperatures allowed to find the optimal combinations for obtaining vesicular nanosystems, the composition of which remains unchanged up to 28 days. These results are promising to refine the development of potential bioactive nanocarriers to be applied in the biomedical and pharmaceutical fields.

Growth and morphologic response of rumen methanogenic archaea and bacteria to cashew nut shell liquid and its alkylphenol components.

The growth and morphology of rumen methanogenic archaea (15 strains of 10 species in 5 genera, including 7 strains newly isolated in the present study) and bacteria (14 species in 12 genera) were investigated using unsupplemented in vitro pure cultures and cultures supplemented with cashew nut shell liquid (CNSL) and its phenolic compound components, anti-methanogenic agents for ruminant animals. Growth of most of the methanogens tested was inhibited by CNSL and alkylphenols at different concentrations ranging from 1.56 to 12.5μg/ml. Of the alkylphenols tested, anacardic acid exhibited the most potent growth inhibition. Three gram-negative bacterial species involved in propionate production were resistant to CNSL and alkylphenols (>50 μg/ml). All the methanogens and bacteria that were sensitive to CNSL and alkylphenols exhibited altered morphology; disruption of the cell surface was notable, possibly due to surfactant activity of the tested materials. Cells division was inhibited in some organisms, with cell elongation and unclear septum formation observed. These results indicate that CNSL and alkylphenols, particularly anacardic acid, inhibit both rumen bacteria and methanogens in a selective manner, which could help mitigate rumen methane generation.

Feeding cashew nut shell liquid decreases methane production from feces by altering fecal bacterial and archaeal communities in Thai local ruminants.

The effect of feeding cashew nut shell liquid (CNSL) on fecal fermentation products and microbiota was investigated in Thai native cattle and swamp buffaloes. Four of each animal were fed rice straw and concentrate diet with control pellets without CNSL for 4weeks, followed by the same diet with pellets containing CNSL for another 4weeks, so that CNSL was administered at a level of 4g/100kg body weight. Feces were collected the last 2days in each feeding period. CNSL alkyl phenols were recovered from feces (16%-28%) in a similar proportion to those in the diet, indicating that most functional anacardic acid was not selectively removed throughout the digestive tract. In vitro production of gas from feces, particularly methane, decreased with CNSL feeding. The proportion of acetate in feces decreased with CNSL feeding, whereas that of propionate increased, without affecting total short-chain fatty acid concentration. CNSL feeding changed fecal microbial community, particularly in swamp buffaloes, which exhibited decreases in the frequencies of Treponema, unclassified Ruminococcaceae, and Methanomassiliicoccaceae. These results suggest that CNSL feeding alters not only rumen fermentation but also hindgut fermentation via modulation of the microbial community, thereby potentially attenuating methane emission from the feces of ruminant animals.

Cashew nutshell liquid catalyzed green chemistry approach for synthesis of a Schiff base and its divalent metal complexes: molecular docking and DNA reactivity

Cashew Nut Shell Liquid (CNSL) anacardic acid was used, for the first time, as a green and natural effective catalyst for the synthesis of a quinoline based amino acid Schiff base ligand from the condensation of 2-hydroxyquinoline-3-carbaldehyde with l-tryptophan via solvent-free simple physical grinding technique. The use of the nontoxic CNSL natural catalyst has many benefits over toxic reagents and the desired product was obtained in high yield in a short reaction time. The procedure employed is simple and does not involve column chromatography. Moreover, a series of metal(II) complexes (metal = iron(II), cobalt(II), nickel(II), and copper(II)) supported by the synthesized new quinoline based amino acid Schiff base ligand (L) has been designed and the compositions of the metal(II) complexes were examined by various analytical techniques. The findings imply that the 2-hydroxyquinoline-3-carbaldehyde amino acid Schiff base (L) serves as a dibasic tridentate ONO ligand and synchronizes with the metal(II) in octahedral geometry in accordance with the general formula [M(LH)2]. Molecular docking study of the metal(II) complexes with B-DNA dodecamer has revealed good binding energy. The conductivity parameters in DMSO suggest the existence of nonelectrolyte species. The interaction of these metal complexes with CT-DNA has shown strong binding via an intercalative mode with a different pattern of DNA binding, while UV-visible photo-induced molecular cleavage analysis against plasmid DNA using agarose gel electrophoresis has revealed that the metal complexes exhibit photo induced nuclease activity.

Anacardic 6-pentadecyl salicylic acid induces apoptosis in breast cancer tumor cells, immunostimulation in the host and decreases blood toxic effects of taxol in an animal model

Many antineoplastic agents induce myelosuppression and leukopenia as secondary effects in patients. The development of anticancer agents that simultaneously provoke antitumor immune response represents an important therapeutic advance. The administration of 6-pentadecyl salicylic acid (6SA) contributes to the antitumor immunity using 4T1 breast cancer cells in Balb/c female mice, with Taxol as a positive control and in cotreatment with 6SA (6SA + Taxol; CoT).Our results show that 6SA reduces tumor volume and size by inducing caspase-8-mediated apoptosis without reducing tumor infiltrated lymphocytes. Also, 6SA reduced lung metastasis and increased the proportion of immune cells in blood, lymph nodes and bone marrow; more evidently, in the proportion of tumor-infiltrated natural killer (NK) cells and cytotoxic T lymphocytes. Taxol reduces helper and cytotoxic lymphocytes causing systemic immunosuppression and myelosuppression in bone marrow, whereas 6SA does not decrease any immune cell subpopulations in circulating blood and lymph nodes. More importantly, the CoT decreased the Taxol-induced cytotoxicity in circulating T cells and bone marrow. Treatment with 6SA increases the secretion of IL-2, IL-12, GM-CSF, TNF-α and IFN-γ and significantly reduces IL-10 and IL-17 secretion, suggesting that the reduction of regulatory T cells and tumor-associated macrophages contribute to the host control of tumor development.Finally, 6SA has an effective antineoplastic activity against breast cancer cells in an immunocompetent animal, reduces the myelosuppression and leukopenia that Taxol produces, improves the antitumoral immunological microenvironment and increases the overall survival of the animals improving the quality of life of patients with cancer.

Exogenous hormone on episperm development and ginkgolic acid accumulation in Ginkgo biloba L

Ginkgolic acid is an anacardic acid specifically distributes in the seeds, leaves and episperms of Ginkgo biloba L. Ginkgolic acid possesses multiple biological functions on disease resistance and pesticide. Ginkgolic acid is enriched in the episperm of G. biloba, which is usually disposed as garbage. Although enriched, the content of ginkgolic acid in episperm is still low, and the extraction process is tedious and costly, which limits its application. In this study, we systematically observed the development process of G. biloba episperm, and detected the variation of endogenous hormone and ginkgolic acid levels therein. The results indicated that auxin, cytokinin and gibberellin (GA1 and GA3) content dramatically varied during the whole development process, indicating their regulation roles in episperm development. Remarkably, the salicylic acid (SA) content showed a significantly positive correlation with ginkgolic acid content. Based on these findings, we implemented exogenous hormone treatment with an optimized combination (300 mg/L NAA + 100 mg/L 6-BA + 200 mg/L SA) on the developing fruits of G. biloba, which resulted in a 53.92% increase of episperm yield and a 21.63% increase of ginkgolic acid content. Our study not only clarified the key development events of G. biloba episperm, the ginkgolic acid content profile, and their relationship, but also provides a cheap and easy way to improve ginkgolic acid accumulation in G. biloba seeds.

Anacardic Acid Complexes as Possible Agents Against Alzheimer's Disease Through Their Antioxidant, In vitro, and In silico Anticholinesterase and Ansiolic Actions.

The frequency of Alzheimer's disease (AD) is growing rapidly with longer life expectancy and the consequent increase of people with a high risk of neurodegenerative diseases. Anacardic acid (AA) has several pharmacological actions, such as antioxidants, anticholinesterase, and anti-inflammatory, which are related to the protection against aging disorders. Also, the metals copper and zinc are co-factors of antioxidant enzymes that can be associated with AA to improve brain-protective action. This study aimed to evaluate the potential of AA metal complexes using copper and zinc chelators to produce potential agents against Alzheimer's disease. For this purpose, Cu and Zn were linked to AA in the ratio of 1:1 in a basic medium. The complexes' formation was confirmed by ultraviolet and visible spectroscopy. The toxicity was evaluated in the zebrafish model, and other information related to AD was obtained using the zebrafish model of anxiety. AA-Zn and AA-Cu complexes showed better antioxidant action than free AA. In the anti-AChE activity, AA was like the AA-Cu complex. In models using adult zebrafish, no toxicity for AA complexes was found, and in the locomotor model, AA-Cu demonstrated possible anxiolytic action. In in silico experiments comparing AA and AA-Cu complex, the coupling energy with the enzyme was lower for the AA-Cu complex, showing better interaction, and also the distances of the active site amino acids with this complex were lower, similar to galantamine, the standard anti-AChE inhibitor. Thus, AA-Cu showed interesting results for more detailed study in experiments related to Alzheimer's disease.

Anacardic acid-mediated regulation of osteoblast differentiation involves mitigation of inflammasome activation pathways.

Disruption of the finely tuned osteoblast-osteoclast balance is the underlying basis of several inflammatory bone diseases, such as osteomyelitis, osteoporosis, and septic arthritis. Prolonged and unrestrained exposure to inflammatory environment results in reduction of bone mineral density by downregulating osteoblast differentiation. Earlier studies from our laboratory have identified that Anacardic acid (AA), a constituent of Cashew nut shell liquid that is used widely in traditional medicine, has potential inhibitory effect on gelatinases (MMP2 and MMP9) which are over-expressed in numerous inflammatory conditions (Omanakuttan et al. in Mol Pharmacol, 2012 and Nambiar et al. in Exp Cell Res, 2016). The study demonstrated for the first time that AA promotes osteoblast differentiation in lipopolysaccharide-treated osteosarcoma cells (MG63) by upregulating specific markers, like osteocalcin, receptor activator of NF-κB ligand, and alkaline phosphatase. Furthermore, expression of the negative regulators, such as nuclear factor-κB, matrix metalloproteinases (MMPs), namely MMP13, and MMP1, along with several inflammatory markers, such as Interleukin-1β and Nod-like receptor protein 3 were downregulated by AA. Taken together, AA expounds as a novel template for development of potential pharmacological therapeutics for inflammatory bone diseases.

Larvicidal Activity of Aedes Aegypti from a Simple Preparation of Cashew (Anacardium occidentale L.) Nut Shell Extract for Community Level Use

Dengue fever is a major risk to public health due to the recent worldwide spread. Chemical vector control areusually considered, therefore, negative consequences are commonly occurred due to chemical resistance andenvironmental effects. Volume of cashew nut shell is become increasing as by-product after nut processing.This study was aimed to evaluate larvicial activity and toxicity of cashew shell extract with simple preparationfor community use. Fresh cashew nut shell was dried and grinded in powder form. Material was immersed inwater tank for 72 h and ratio of flavor and material and water ratio was 100 g/L (10% W/V). The supernatantof stock solution was diluted to 1:5, 1:10, 1:20, 1:50 and 1:100 of larvicidal solution for phenolic contentmeasurement, analysis of alkyl phenols by gas chromatography-mass spectrometry (GC/MS) and larvicialactivity test. Larvicidal activity was effective at LC50 = 3.8 mg of GAE/ml; LC90 = 11.5 mg of gallic acidequivalent (GAE) /ml. The solution was contained five alkyl phenols, which included saturated cardol,monounsaturated cardol, anacardic acid, diunsaturated cardanol and monounsaturated cardanol. Anacardicacid was major active compound, which was correlated to mass spectra. This larvicidal solution preparationwas simple and cost effectiveness, which may useful in community level especially in cashew cultivatingarea. Field application and public training on this study will be conduct on controlling of mosquito-bornediseases.

Electrosynthesized metal-organic framework: a dual-modality readout platform for Cu(II), coenzyme A and histone acetyltransferase analysis

A novel dual-modality readout biosensing method is developed for Cu(II), coenzyme (CoA) and histone acetyltransferase (HAT) analysis based on an electrosynthesized tris(bipyridine)ruthenium(II)-functionalized metal-organic framework (Ru-MOF). In this protocol, the Ru-MOF with a delicate structure serves as both an electrochemiluminescent (ECL) and fluorescent (FL) probe. Interestingly, Cu(II) can hinder the two distinct processes favorably, thus realizing bidirectional detection of Cu(II) via an “on-off” method. Simultaneously, CoA, which contains a sulfhydryl group, can ignite a reverse “off-on” process due to the polymeric interaction of CoA and Cu(II) (2: 1). Similarly, abundant CoA molecules could also be generated regularly by a typical HAT p300-driven acetylation reaction, hence accomplishing HAT p300 activity analysis. Subsequently, an ingenious “on-off” route is exhibited again by the introduction of some small molecules (including anacardic acid and C646), which present an inhibiting effect on HAT p300 activity. Furthermore, quantitative analysis of Cu(II), CoA and HAT p300 (ECL/FL) is achieved brightly with detection limits of 0.19/0.76 nM, 1.3/6.5 nM and 1.5/8.8 nM, respectively. Ultimately, this two-channel biosensor with excellent analytical performance is applied successfully in real samples, demonstrating its potential use in bioanalysis.

High glucose-induced oxidative stress accelerates myogenesis by altering SUMO reactions

Skeletal muscle preservation is a dynamic process that involves constant repair and regeneration. However, the regenerative capacity of muscle cells declines in hyperglycemia. This study aimed to explore the molecular mechanisms underlying this glucotoxicity during myoblast differentiation. C2C12 cells were exposed to different concentrations of glucose, to recapitulate the development of skeletal muscles in vivo in normo- and hyperglycemic conditions. In high glucose conditions, we found significant increases in levels of total cellular reactive oxygen species (ROS) and a reorganization of SUMO enzyme transcripts and SUMOylated proteins. Furthermore, in anticipation of the ROS-induced damage to newly formed myotubes, we observed acceleration of myogenesis. Interestingly, we found a tight relationship between SUMOylation of the Histone methyltransferase SET7/9 and the maintenance of sarcomeric structures of newly formed myotubes. Finally, treatment with the antioxidant anacardic acid preserved the function and activity of myotubes generated in high-glucose conditions by interfering with both ROS and SUMO pathways. Combined, these results suggest that increased oxidative stress and modulation of SUMO reactions are key mediators of glucotoxicity and inhibition of these perturbations using antioxidants might improve muscle regeneration in hyperglycemia.

Anacardic acid induces IL-33 and promotes remyelination in CNS

Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anacardic acid to cultured oligodendrocyte precursor cells (OPCs) rapidly increased expression of myelin genes and myelin proteins, suggesting a direct induction of genes involved in myelination by anacardic acid. Also, when added to OPCs, anacardic acid resulted in the induction of IL-33. In vivo, treatment of with anacardic acid in doses which ranged from 0.025 mg/kg to 2.5 mg/kg, improved pathologic scores in experimental allergic encephalitis (EAE) and in the cuprizone model of demyelination/remyelination. Electron microscopic studies performed in mice fed with cuprizone and treated with anacardic acid showed lower g-ratio scores when compared to controls, suggesting increased remyelination of axons. In EAE, improvement in paralytic scores was seen when the drug was given prior to or following the onset of paralytic signs. In EAE and in the cuprizone model, areas of myelin loss, which are likely to remyelinate, was associated with a greater recruitment of IL-33-expressing OPCs in mice which received anacardic acid when compared to controls.

Sodium oleate, arachidonate, and linoleate enhance fibrinogenolysis by Russell's viper venom proteinases and inhibit FXIIIa; a role for phospholipase A2 in venom induced consumption coagulopathy

Life-threatening symptoms produced by Russell's viper (RV, Daboia russelii) envenomation result largely from venom induced consumption coagulopathy (VICC). VICC is thought to be mediated to a large degree by venom serine and metalloproteinases, as well as by snake venom phospholipase A2 (svPLA2), the most abundant constituent of RV venom (RVV). The observation that the phenolic lipid anacardic acid markedly enhances proteolytic degradation of fibrinogen by RVV proteinases led us to characterize the chemical basis of this phenomenon with results indicating that svPLA2 products may be major contributors to VICC. ResultsOf the chemical analogs tested, the anionic detergents sodium dodecyl sulfate, sodium deoxycholate, N-lauryl sodium sarcosine, and the sodium salts of the fatty acids arachidonic, oleic and to a lesser extend linoleic acid were able to enhance fibrinogenolysis by RVV proteinases. Enhanced Fibrinogenolysis (EF) was observed with various venom size exclusion fractions containing different proteinases, and also with trypsin, indicating that conformational changes of the substrate and increased accessibility of otherwise cryptic cleavage sites are likely to be responsible for EF. In addition to enhancing fibrinogenolysis, sodium arachidonate and oleate were found to partially inhibit thrombin induced, factor XIIIa (FXIIIa) mediated ligation of fibrin chains. In clotting experiments with fresh blood RVV was found to disrupt normal coagulation, leading to small, partial clot formation, whereas RVV pretreated with the PLA2 inhibitor Varespladib induced rapid and complete clot formation (after 5 min) compared to blood alone. ConclusionThe observations that fatty acid anions and anionic detergents induce conformational changes that render fibrin(ogen) more susceptible to proteolysis by RVV proteinases and that RVV-PLA2 activity (which produces FFA) is required to render blood incoagulable in clotting experiments with RVV indicate a mechanism by which the activity of highly abundant RVV-PLA2 promotes degradation and depletion of fibrin(ogen) resulting in incoagulable blood seen following RVV envenomation (VICC).

Poison ivy hairy root cultures enable a stable transformation system suitable for detailed investigation of urushiol metabolism.

Poison ivy (Toxicodendron radicans) is best known for causing exasperating allergenic delayed‐contact dermatitis symptoms that last for weeks on persons who have contacted the plant. Urushiols are alkylcatechols produced by poison ivy responsible for causing this dermatitis. While urushiol chemical structures are well known, the metabolic intermediates and genes responsible for their biosynthesis have not been experimentally validated. A molecular genetic characterization of urushiol biosynthesis in poison ivy will require stable genetic transformation and subsequent regeneration of organs that retain the capacity synthesize urushiol. To this end, Agrobacterium rhizogenes was used to generate hormone‐independent poison ivy hairy root cultures. Optimal conditions for hairy root formation were skotomorphic poison ivy hypocotyls prick‐inoculated with A. rhizogenes, and preferential propagation of cultures with an atypical clumpy hairy root growth habit. The origin of the poison ivy accession used for A. rhizogenes prick‐inoculation did not affect the initial formation of calli/hairy root primordia, but rather significantly influenced the establishment of long‐term hormone‐independent hairy root growth. A. rhizogenes harboring a recombinant T‐DNA binary plasmid with an intron‐containing Firefly Luciferase gene produced stable transgenic hairy root lines expressing luciferase activity at high frequency. Poison ivy hairy root lines produced significantly lower steady‐state urushiol levels relative to wild‐type roots, but higher urushiol levels than a poison ivy undifferentiated callus line with undetectable urushiol levels, suggesting that urushiol biosynthesis requires intact poison ivy organs. The lower urushiol levels in poison ivy hairy root lines facilitated the first identification of anacardic acid metabolites initially in hairy roots, and subsequently in wild‐type roots as well. This study establishes a transformation hairy root regeneration protocol for poison ivy that can serve as a platform for future reverse‐genetic studies of urushiol biosynthesis in poison ivy hairy roots.

Anti-Inflammatory, Antinociceptive, and Antioxidant Properties of Anacardic Acid in Experimental Models.

Anacardic acid (AA), a compound extracted from cashew nut liquid, exhibits numerous pharmacological activities. The aim of the current investigation was to assess the anti-inflammatory, antinociceptive, and antioxidant activities of AA in mouse models. For this, Swiss albino mice were pretreated with AA (10, 25, 50 mg/kg, intraperitoneally, ip) 30 min prior to the administration of carrageenan, as well as 25 mg/kg of prostaglandin E2, dextran, histamine, and compound 48/80. The antinociceptive activity was evaluated by formalin, abdominal, and hot plate tests, using antagonist of opioid receptors (naloxene, 3 mg/kg, ip) to identify antinociceptive mechanisms. Results from this study revealed that AA at 25 mg/kg inhibits carrageenan-induced edema. In addition, AA at 25 mg/kg reduced edema and leukocyte and neutrophilic migration to the intraperitoneal cavity, diminished myeloperoxidase activity and malondialdehyde concentration, and increased the levels of reduced glutathione. In nociceptive tests, it also decreased licking, abdominal writhing, and latency to thermal stimulation, possibly via interaction with opioid receptors. Taken together, these results indicate that AA exhibits anti-inflammatory and antinociceptive actions and also reduces oxidative stress in acute experimental models, suggesting AA as a promising compound in the pharmaceutical arena.

The Anti-Inflammatory Effects of Anacardic Acid on a TNF-α - Induced Human Saphenous Vein Endothelial Cell Culture Model.

Coronary bypass operations are commonly performed for the treatment of ischemic heart diseases. Coronary artery bypass surgery with autologous human saphenous vein maintains its importance as a commonly used therapy for advanced atherosclerosis. Vascular inflammation-related intimal hyperplasia and atherosclerotic progress have major roles in the pathogenesis of saphenous vein graft disease. In our study, we investigated the effect of anacardic acid (AA), which is a bioactive phytochemical in the shell of Anacardium occidentale, on atherosclerosis considering its inhibitory effect on NF-κB. We observed relative ICAM-1 and NF-κB mRNA levels by qRT-PCR method in a TNF-α- induced inflammation model of saphenous vein endothelial cell culture after 0.1, 0.5, 1 and 5 μM of AA were applied to the cells. In addition, protein levels of ICAM-1 and NF-κB were evaluated by immunofluorescent staining. The results were compared between different concentrations of AA, and also with the control group. It was found that 5 μM, 1 μM and 0.5 μM of AA had toxic effects, while cytotoxicity decreased when 0.1 μM of AA was applied both alone and with TNF-α. When AA was applied with TNF-α, there was a decrease and suppression in NF-κB expression compared with the TNF-α group. TNF-α-induced ICAM-1 expression was significantly reduced more in the AA-applied group than in the TNF-α group. In accordance with our results, it can be said that AA has a protective role in the pathogenesis of atherosclerosis and hence in saphenous vein graft disease.