Ninety-day toxicity and genotoxic effects of synthetically derived fully saturated forms of anacardic acid in mice.

Organically synthesized fully saturated form of Anacardic acid (AA) has previously shown to be effective in the treatment of inflammatory autoimmune disease. In this study, organically synthesized fully saturated form of AA was orally administered to male and female Swiss albino mice for 90 consecutive days at doses of 25, 50 and 100 mg/kg BW (n = 20 per sex/group). Administration of AA was well tolerated at all dose levels. The treated animals did not show a dose-response toxicity in their hematology, liver, or metabolic profile. Minimally significant changes in serum biochemistry and hematology parameters were noted, but these were not considered to be of biological or toxicological importance and were not outside the known accepted ranges. Sporadic differences in organ weights were observed between groups, but all were minimal (<10%) and unlikely to indicate toxicity. The incidence of histopathological lesions was comparable between treated and control groups across all tested organs. Based upon these findings, the no-observed-adverse-effect level was determined to be ≥ 100 mg/kg BW, which was the highest dose tested. There were no genotoxic (mutagenic and clastogenic) effects seen in In-vivo micronucleus test, In-vitro chromosomal aberration test and Bacterial reverse mutation test. These results support, no genotoxicity and no toxicity associated with oral consumption of AA in mice as a dietary supplement for beverages and food.

Synergy of histone acetyltransferase inhibitor (HATi) with quercetin inhibits biofilm formation in Candida tropicalis.

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid (AA), and quercetin, a known flavonoid, significantly prevented biofilm formation by C. tropicalis. We further show that C. tropicalis exhibited a considerable downregulation of drug-resistance gene expression (CDR1 and MDR1) when co-administrated. Additionally, in silico studies revealed that the AA interacts strongly with a histone acetyltransferase, Rtt109, which may account for the observed biofilm inhibitory effect. In conclusion, the study illustrates how HATi may be used to potentiate the inhibitory action of phytoactives or antifungals against drug-resistant yeast infections.

Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability.

Anacardic acid (AnAc) inhibits the growth of estrogen receptor α (ERα)-positive MCF-7 breast cancer (BC) cells and MDA-MB-231 triple-negative BC (TNBC) cells, without affecting primary breast epithelial cells. RNA sequencing (seq) and network analysis of AnAc-treated MCF-7 and MDA-MB-231 cells suggested that AnAc inhibited lipid biosynthesis and increased endoplasmic reticulum stress. To investigate the impact of AnAc on cellular metabolism, a comprehensive untargeted metabolomics analysis was performed in five independent replicates of control versus AnAc-treated MCF-7 and MDA-MB-231 cells and additional TNBC cell lines: MDA-MB-468, BT-20, and HCC1806. An analysis of the global metabolome identified key metabolic differences between control and AnAc-treated within each BC cell line and between MCF-7 and the TNBC cell lines as well as metabolic diversity among the four TNBC cell lines, reflecting TNBC heterogeneity. AnAc-regulated metabolites were involved in alanine, aspartate, glutamate, and glutathione metabolism; the pentose phosphate pathway; and the citric acid cycle. Integration of the transcriptome and metabolome data for MCF-7 and MDA-MB-231 identified Signal transduction: mTORC1 downstream signaling in both cell lines and additional cell-specific pathways. Together, these data suggest that AnAc treatment differentially alters multiple pools of cellular building blocks, nutrients, and transcripts resulting in reduced BC cell viability.

Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-High-Resolution Mass Spectrometry for Distinguishing the Origin of Ellagic Acid Extracts: Pomegranate Peels or Gallnuts.

Ellagic acid, known for its various biological activities, is widely used. Ellagic acid from pomegranate peels is safe for consumption, while that from gallnuts is only suitable for external use. However, there is currently no effective method to confirm the source of ellagic acid. Therefore, this study establishes an analysis method using ultra-high-performance liquid chromatography-electrospray ionization-high-resolution mass spectrometry (UHPLC-ESI-HR-MS) to identify the components of crude ellagic acid extracts from pomegranate peels and gallnuts. The analysis revealed that there was a mix of components in the crude extracts, such as ellagic acid, palmitic acid, oleic acid, stearic acid, and 9(10)-EpODE. Furthermore, it could be observed that ellagic acid extracted from gallnuts contained toxic substances such as anacardic acid and ginkgolic acid (15:1). These components could be used to effectively distinguish the origin of ellagic acid from pomegranate peels or gallnuts. Additionally, a rapid quantitative analysis method using UHPLC-ESI-MS with multiple reaction monitoring (MRM) mode was developed for the quality control of ellagic acid products, by quantifying anacardic acid and ginkgolic acid (15:1). It was found that one of three ellagic acid health care products contained ginkgolic acid (C15:1) and anacardic acid at more than 1 ppm.

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.

Treatment with anacardic acid modulates dendritic cell activation and alleviates the disease development of autoimmune neuroinflammation in mice.

Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.

Calcium anacardate as source of anacardic acid in laying Japanese quail diet.

Anacardic acid is naturally found in various parts of the cashew tree (Anacardium occidentale L.) and marketed as calcium anacardate. This product has antibacterial, antifungal and antioxidant activity, and has been used in humans in the treatment and prevention of cardiovascular and cerebrovascular diseases and tumors. In meat and egg production systems, anacardic acid is used as a substitute for growth-promoting antibiotics. The study objective was to evaluate effects of adding calcium anacardate as source of anacardic acid in laying Japanese quail diet on bird performance and eggs quality. A total of 252 Japanese quail with 22 week-old were studied, using a completely randomized design composed of six treatments with six replicates and seven quails per experimental unit. Treatments applied were: diet without growth promoter; diet with 0,1% growth promoter; and four diets without growth promoter and addition of 0.25; 0.50; 0.75 and 1.0% calcium anacardate (CA), respectively. The data were submitted to analysis of variance and treatment means compared with a SNK test (5%). The data from treatments containing CA were submitted to regression analysis. Treatments did not influence feed intake, egg production, egg weight, egg volume, feed conversion ratio and eggs quality parameters. The addition up to 1% of calcium anacardate in laying Japanese quail diet, does not influence their performance and egg quality.

Anacardic Acid Derivatives Affect the in Vitro Reactions of Photosynthesis.

The dichloromethane extract of the cashew nuts from Anacardium occidentale was fractionated by rotation locular countercurrent chromatography aimed at discovering metabolites that could be useful as new models for photosynthesis inhibitors. The chemical fractionation afforded a complex mixture of anacardic acids, which upon catalytic hydrogenation yielded anacardic acid (1). Methylation of 1 via reaction with diazomethane afforded an ester 2. Both compounds were evaluated using polarographic approaches and fluorescence studies of chlorophyll a (ChL a). The in vitro assays informed the decision for the classification of 1 and 2 as Hill reaction inhibitors. Besides that, 1 inhibited the donor side of the PSII, while 2 acted as an energy transfer inhibitor. Therefore, this study is important for the development of herbicides.

Cashew (Anacardium occidentale) Nut-Shell Liquid as Antioxidant in Bulk Soybean Oil.

Recently, natural antioxidants for the food industry have become an important focus. Cashew nut-shell liquid (CNSL) is composed of compounds that can act as natural antioxidants in food systems. The aim of this work was to evaluate the potential of CNSL and its components to act as natural antioxidants in a bulk oil system. CNSL was treated with calcium hydroxide to obtain two fractions [cardol/cardanols acid fraction (CCF) and anacardic acid fraction (AF)]. CNSL, FF and AF were analyzed by thin-layer chromatography and Fourier-transform infrared spectroscopy. The protective effects of CNSL, CCF and AF were tested in terms of the peroxide value of bulk soybean oil in accelerated assays and were compared against controls with and without synthetic antioxidants (CSA and CWA). CNLS, CCF, AF and CSA were tested at 200 mg/kg soybean oil by incubation at 30, 40, 50 and 60 °C for five days. The activation energy (Ea) for the production of peroxides was calculated by using the linearized Arrhenius equation. Thin-layer chromatography and Fourier-transform infrared spectroscopy revealed that (i) CNSL contained cardanols, anacardic acids, and cardols; (ii) CCF contained cardanols and cardols; and (iii) AF contained anacardic acids. CSA (Ea 35,355 J/mol) was the most effective antioxidant, followed by CCF (Ea 31,498 J/mol) and by CNSL (Ea 26,351 J/mol). AF exhibited pro-oxidant activity (Ea 8339 J/mol) compared with that of CWA (Ea 15,684 J/mol). Therefore, cardols and cardanols from CNSL can be used as a natural antioxidant in soybean oil.

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.

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-1ß 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.

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 Acids from Amphipterygium adstringens Confer Cytoprotection against 5-Fluorouracil and Carboplatin Induced Blood Cell Toxicity While Increasing Antitumoral Activity and Survival in an Animal Model of Breast Cancer.

Amphipterygium adstringens (cuachalalate) contains anacardic acids (AAs) such as 6-pentadecyl salicylic acid (6SA) that show immunomodulatory and antitumor activity with minimal or no secondary adverse effects. By contrast, most chemotherapeutic agents, such as 5-fluorouracil (5-FU) and carboplatin (CbPt), induce myelosuppression and leukopenia. Here, we investigated the myeloprotective and antineoplastic potential of an AA extract or the 6SA as monotherapy or in combination with commonly used chemotherapeutic agents (5-FU and CbPt) to determine the cytoprotective action of 6SA on immune cells. Treatment of Balb/c breast tumor-bearing female mice with an AA mixture or 6SA did not induce the myelosuppression or leukopenia observed with 5-FU and CbPt. The co-administration of AA mixture or isolated 6SA with 5-FU or CbPt reduced the apoptosis of circulating blood cells and bone marrow cells. Treatment of 4T1 breast tumor-bearing mice with the AA mixture or 6SA reduced tumor growth and lung metastasis and increased the survival rate compared with monotherapies. An increased effect was observed in tumor reduction with the combination of 6SA and CbPt. In conclusion, AAs have important myeloprotective and antineoplastic effects, and they can improve the efficiency of chemotherapeutics, thereby protecting the organism against the toxic effects of drugs such as 5-FU and CbPt.

Purified anacardic acids exert multiple neuroprotective effects in pesticide model of Parkinson's disease: in vivo and in silico analysis.

Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1ß, cleaved IL-1ß, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1ß, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1ß in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1ß and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.

Anacardic acid inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo.

Postmenopausal osteoporosis is the most common form of primary osteoporosis, and the incidence of the condition is rapidly increasing. In consideration of the limitations of current therapeutic options for the treatment of postmenopausal osteoporosis, there is an urgent need to develop safer alternatives. Anacardic acid, a natural phenolic acid compound extracted from cashew nut shell, possesses potent antitumor and anti-inflammatory effects and inhibits NF-κB signaling. However, its effect on osteoclasts remains unknown. This study reports the first evidence for the antiosteoclastogenic and antiresorptive effects of anacardic acid on bone marrow-derived macrophage-derived osteoclasts. Mechanistically, anacardic acid disrupts the phosphorylation of TGF-ß activated kinase 1 and subsequently suppresses multiple receptor activator of NF-κB ligand-induced signaling cascades, ultimately inhibiting the induction and activation of the crucial osteoclast transcriptional factor nuclear factor of activated T-cell cytoplasmic 1. Consistent with cellular results in vitro, anacardic acid treatment improves bone density in the murine model of ovariectomy-induced bone loss. Taken together, our study provides promising evidence for the therapeutic application of anacardic acid as a new potential pharmacological treatment for osteoporosis.-Zhao, K., Jia, Y., Peng, J., Pang, C., Zhang, T., Han, W., Jiang, J., Lu, X., Zhu, J., Qian, Y. Anacardic acid inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo.

Differential lethal action of C17:2 and C17:0 anacardic acid derivatives in Trypanosoma cruzi - A mechanistic study.

The n-hexane extract from leaves of Schinus terebinthifolius (Anacardiaceae) induced 100% of death of trypomastigote forms of T. cruzi at 300 µg/mL and was subjected to a bioactivity-guided fractionation to afford a C17:2 derivative of anacardic acid [6-(8'Z,11'Z)-heptadecadienyl-salicylic acid, 1]. Additionally, compound 1 was subjected to hydrogenation procedures to afford a C17:0 derivative (6-heptadecanyl-salicylic acid, 1a). Compounds 1 and 1a were effective in killing trypomastigote forms of T. cruzi with IC50 values of 8.3 and 9.0 µM, respectively, while a related compound, salicylic acid, was inactive. Furthermore, no cytotoxicity was observed for the highest tested concentration (CC50 > 200 µM) for all evaluated compounds. Due to the promising results, the mechanism of parasite death was investigated for compounds 1 and 1a using flow cytometry and spectrofluorimetry. The cell membrane permeability assay with SYTOX Green indicated that compound 1 significantly altered this parameter after 40 min of incubation, while compound 1a caused no alteration. Considering that the hydrogenation rendered a differential cellular target in parasites, additional assays were performed with 1a. Despite no permeabilization of the plasma membrane, compound 1a induced depolarization of the electric potential after two hours of incubation. The mitochondria of the parasite were also affected by compound 1a, with depolarization of the mitochondrial membrane potential, and reduction of reactive oxygen species (ROS) levels. The Ca2+ levels were not affected during the time of incubation. Considering that the mitochondrion is a single organelle in Trypanosoma cruzi for ATP generation, compounds affecting the bioenergetic system are of interest for drug discovery against Trypanosomatids.

Anacardic acid attenuates pressure-overload cardiac hypertrophy through inhibiting histone acetylases.

Cardiac hypertrophy has become a major cardiovascular problem wordwide and is considered the early stage of heart failure. Treatment and prevention strategies are needed due to the suboptimal efficacy of current treatment methods. Recently, many studies have demonstrated the important role of histone acetylation in myocardium remodelling along with cardiac hypertrophy. A Chinese herbal extract containing anacardic acid (AA) is known to possess strong histone acetylation inhibitory effects. In previous studies, we demonstrated that AA could reverse alcohol-induced cardiac hypertrophy in an animal model at the foetal stage. Here, we investigated whether AA could attenuate cardiac hypertrophy through the modulation of histone acetylation and explored its potential mechanisms in the hearts of transverse aortic constriction (TAC) mice. This study showed that AA attenuated hyperacetylation of acetylated lysine 9 on histone H3 (H3K9ac) by inhibiting the expression of p300 and p300/CBP-associated factor (PCAF) in TAC mice. Moreover, AA normalized the transcriptional activity of the heart nuclear transcription factor MEF2A. The high expression of cardiac hypertrophy-linked genes (ANP, ß-MHC) was reversed through AA treatment in the hearts of TAC mice. Additionally, we found that AA improved cardiac function and survival rate in TAC mice. The current results further highlight the mechanism by which histone acetylation is controlled by AA treatment, which may help prevent and treat hypertrophic cardiomyopathy.

The antineoplastic agent anacardic 6-pentadecyl salicylic acid produces immunomodulation in vivo via the activation of MAPKs.

Anacardic 6-pentadecyl salicylic acid (6SA) is the active component of Amphipterygium adstringens, a plant used in traditional medicine for the treatment of malaria and vascular diseases and as an anti-bacterial and immune-modulatory agent. However, the effect of 6SA on the immune system remains unclear. In this study, we examined the immune-stimulatory activity of 6SA in 6-8-week-old female BALB/c mice. We found that treatment with 2 mg/kg of 6SA increased the proportions of macrophages after 7 and 14 days of treatment and of natural killer (NK) cells after 14 days of treatment in circulating blood. In lymph nodes, treatment with 6SA for 14 days increased the number of macrophages. In addition, 6SA increases in the systemic levels of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-12, IL-6 and IL-1ß and of nitric oxide (NO). We observed an increase in the secretion of Granulocyte/Macrophage Colony Stimulation Factor (GM-CSF) that could explain the increase in the proportion of macrophages. Moreover, 6SA induced the classical activation of macrophages by increasing their expression of MHC-II and their production of TNF-α. These M1-polarised macrophages presented enhanced phagocytosis and NO secretion. This activation was due to induction of the phosphorylation of MAPKs such as ERK, JNK and p38 because specific inhibitors of the phosphorylation of these MAPKs reduced the 6SA-induced phagocytosis and NO and particularly, the secretion of GM-CSF in macrophages by inhibition of ERK. Despite these effects on macrophages, 6SA does not have any direct effect on the proportion of lymphocytes.

Effect of anacardic acid against echinococcosis through inhibition of VEGF-induced angiogenesis.

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)-induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.

A highly sensitive GC-MS method for simultaneous determination of anacardic acids in cashew (Anacardium occidentale) nut shell oil in the presence of other phenolic lipid derivatives.

The commercial value of cashew nut shell liquid (CNSL) has become a cornerstone of the agrowaste industry. It is the by-product of the cashew industry and has an 1/8 inch thickness of soft honeycomb structure. CNSL contains phenolic lipids with aliphatic chains such as anacardic acid, cardanol, cardol and methyl cardol, and their derivatives. The developed GC-MS method is rapid, accurate and selective using a selected derivatizing reagent, namely N-methyl-N-(trimethylsilyl)-trifluoroacetamide that was previously diluted 1:1% with anhydrous pyridine. The proposed GC-MS method was applied for the analysis of different CNSL samples. The results showed that all classes of CNSL compounds were detected. The four alkyl phenols were detected with their different alkyl sidechains without any interference. This method is also specified for the detection of fatty acids of saturated and unsaturated chains. Silylation did not cause any alteration in the chemical structure of CNSL compounds regardless of esterification action. Silylation is considered a safe derivatizing agent compatible with GC chromatography and specific for all volatile and nonvolatile polar and nonpolar CNSL compounds that could be detected in CNSL samples.