The Ayurvedic medical system uses fruits of the Benincasa hispida plant to treat mental diseases, including schizophrenia. The goal of the current study was to assess the aqueous extract of B. hispida fruit's ability to relieve stress and anxiety induced in zebrafish models using neuropharmacological evaluation, which included determining behavioral parameters in tests such as the T-maze, open tank test (OTT), and light-dark preference test (LDPT). After measuring the zebrafish survival rate for 96 h, the LC50 was found to be 5 µg. AChE (acetylcholinesterase) inhibitory activity and the status of antioxidant enzymes (SOD, CAT, and LDH) were also used to evaluate the toxicity. Furthermore, the administration of the aqueous extract of B. hispida fruit increased the frequency of entry and duration of time spent in the bright section, suggesting a noteworthy reduction in levels of stress and anxiety. Additionally, the antistress and antianxiety activity was confirmed by the docking studies' mechanism of action, which involves the AChE receptor binding stability of the homogalactaconan molecule found in the aqueous extract of B. hispida fruit. Overall, the findings of this study demonstrated that the aqueous extract of B. hispida fruit is a viable therapeutic molecule for the creation of novel drugs and the treatment of stress since it has the therapeutic advantage of reversing the negative effects of stress and anxiety.
Keywords: Benincasa hispida; antianxiety; antistress; behavioral parameters; therapeutic molecule.