Evaluation of Anxiolytic Potential of Ethanolic Extract of Manilkara Zapota L. Leaves in Rat Models

Background: Anxiety disorders, marked by persistent fear and excessive worry, significantly affect daily life. While conventional anxiolytics are effective, their long-term use often leads to side effects, prompting the search for safer, plant-based alternatives. Manilkara zapota L is a traditional medicinal plant used for various ailments. Objective: This study explored the anxiolytic effects of ethanolic extract of Manilkara zapota L. leaves in rats, focusing on its impact on anxiety through behavioral and biochemical assessments Methodology: Powdered leaves of Manilkara zapota L. were extracted using Soxhlet extraction with the 70% ethanol at a 1:10 w:v ratio and 60°C. Phytochemical screening and an acute oral toxicity study were conducted per OECD guidelines 423 over 28 days on four groups of rats: control, standard (diazepam), low dose (100 mg/kg), and high dose (200 mg/kg). Behavioral assessments, including the Elevaed Plus Maze (EPM), Open Field Test (OFT), Hole Board Test (HBT), and rotarod, were conducted weekly to evaluate anxiety and motor function. On day 29, biochemical assays on rat brain homogenates measured monoamine oxidase-A (MAO) activity and lipid peroxidation to assess oxidative stress and neurochemical effects Result: The EEMZ achieved a yield of 15.16% and was confirmed to contain various Phytochemicals such as alkaloids, glycosides, flavonoids, and others. Acute oral toxicity testing, following OECD guidelines 423, showed no mortality at a dose of 2000 mg/kg, leading to the selection of 100 mg/kg and 200 mg/kg for further studies. The study found that a high dose of the extract (200 mg/kg) showed potential anxiolytic effects, comparable to diazepam. Behavioural tests indicated reduced anxiety, evidenced by increased time in open arms of the EPM and central zone of the OFT, enhanced exploratory behaviour, and HBT and Rota-rod performance, indicating no sedation. Biochemical analysis revealed significant MAO activity and lipid peroxidation reductions, suggesting protective effects against oxidative stress, especially in the high-dose group. Conclusion: The ethanolic extract of Manilkara zapota L showed significant anxiolytic effects, improving behavioural and biochemical parameters. This suggests its potential as a natural anxiolytic effect, requiring further exploration to understand its active constituents and mechanisms of action.