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OBJECTIVE: Stress exacerbates the pathophysiology of major neurodegenerative disorders. In this study, the zebrafish ( Danio rerio ), the frequently used model for experimental studies of stress and other central nervous system disorders, was used to evaluate the anxiolytic potential of flavonoids, namely silibinin and naringenin on alleviating acute stress-induced anxiety. MATERIALS AND METHODS: A molecular docking study with Molegro Virtual Docker software was done to assess the binding potential of flavonoids on serotonin and dopamine receptors. To determine the bioactivity and investigate the toxicity of the flavonoids, silibinin, and naringenin, brine shrimp lethality assay, and an acute toxicity study was conducted according to Organization for Economic Co-operation and Development (OECD) Test Guideline 203. The effect of silibinin and naringenin was assessed using behavioral tasks such as the novel tank assay and the light-dark test on the zebrafish model of acute stress. RESULTS: Molecular docking studies showed a higher affinity of silibinin and naringenin for the serotonin and dopamine receptors. In comparison to the LC 50 value, 13.15 μg/ml of the reference standard potassium dichromate, silibinin, and naringenin yielded higher LC 50 values, 34.10 μg/ml and 91.33 μg/ml, respectively. The LC 50 value of silibinin and naringenin was observed to be >100 mg/l from the acute toxicity study on adult zebrafish. After transferring to a novel tank, silibinin and naringenin-treated zebrafish groups were found to explore the upper level of the tank, similar to standard drugs, and spent a long time in the upper level of the tank compared to the control group ( p < 0.01). Both silibinin and naringenin treatment group spent increased amounts of time in the tank's illuminated part in contrast to that of the dark side as evidenced by the number of zebrafish entering or remaining in the illuminated part of the tank through the light-dark test. Silibinin and naringenin treated groups were found to spend increased time in the light side significantly on the day 15 th of evaluation as compared to the control group ( p < 0.05 and p < 0.001, respectively). CONCLUSION: The flavonoids, silibinin, and naringenin were found to mitigate acute stress-induced anxiety, owing to their anxiolytic properties in the zebrafish model and may be explored as the potential therapeutic agents for treating anxiety.

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Objectives: To study the larvicidal effect of Vitex negundo Linn against mosquito larvae by larvicidal bioassay and in silico molecular docking studies. Methods: The larvicidal bioassay of Vitex negundo Linn was assessed by using WHO standard protocol and an in silico molecular docking study was performed by using Molegro Virtual Docker against Culex quinquifasciatus. The early third instar larvae of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus were exposed to the extract concentrations in three replicates and different temephos concentration were taken as positive control and solvent control was also used. Results:The study results shows that of Vitex negundo Linn possess the potential larvicidal activity against third instar larvae of Culex quinquifasciatus when compared to Aedes aegypti L and Aedes albopictus. Percentage mortality and half-maximal effective concentration (EC 50 ) value were calculated against the above mentioned three species like wise Culex quinquifasciatus (83.77 ppm), Aedes aegypti (341.7 ppm), and Aedes albopictus (487.9 ppm). The highest larval mortality was found against Culex quinquifasciatus of 100 % at 500 parts per million. In silico molecular docking studies using Molegro Virtual Docker against Odorant binding protein (PDB: 2L2C) of Culex quinquifasciatus was performed as it showed better results in in vitro study. The results reveal that phytoconstituent like Vitexicarpin showed good docking scores against the Odorant Binding Protein 2L2C and the moldock score of Vitexicarpin was found to be -87.3733, whereas moldock score of standard Azadirachtin was found to be -110.77. Conclusion: The present study reveal that the Vitex negundo Linn possess the potential larvicidal activity against the Culex quinquifasciatus species.