Anxiolytic effect of anacardic acids from cashew (Anacardium occidentale) nut shell in mice

Antianxiety drugs currently in use are associated with a number of serious side effects. Present study was designed to evaluate the efficacy of anacardic acids (AAs) isolated from cashew nut (Anacardium occidentale L.) shell liquid (CNSL) to treat anxiety as well as its role in oxidative stress in mice model. Anxiolytic effect of AA was evaluated using rota-rod and a set of behavioral tests in male Swiss albino mice at the doses of 10, 25, and 50 mg/kg. Flumazenil was used to evaluate the possible involvement of GABAergic system in the mechanism of action of AA. The effect of AA on oxidative stress in mice was evaluated by determining the concentration of malondialdehyde (MDA), reduced glutathione, and catalase (CAT) activity. The detection of DNA damage of the treated animals was performed using alkaline comet test in the hippocampus and frontal cortex of the animals. The results demonstrated that AA did not produce myorelaxant and sedative effects, nor did it cause a decrease in locomotor activity. The anxiolytic effect of AA was well-evident in all tests, especially at higher dose levels (25 and 50 mg/mg). Flumazenil reversed the anxiolytic effect of AA at all doses. In addition, AA reduced oxidative stress by decreasing the concentration of MDA and increasing the levels of reduced glutathione (GSH) and CAT activity. Statistical analysis by Pearson's correlation indicated a positive correlation between anxiolytic effect of AA to its antioxidant and lipid peroxidation inhibitory activity. Furthermore, increased CAT activity and GSH concentrations in the hippocampus and frontal cortex of mice was also complementary to the reduced genotoxic damage observed in the study. In comet assay, AA did not increase in DNA damage. In conclusion, the results supported that AA possesses GABA_A receptor mediated anxiolytic activity with the lack of myorelaxation and genotoxicity. © 2018 IUBMB Life, 70(5):420-431, 2018.