Antidepressant Effects of Betulin: Mechanistic Insights and Therapeutic Potential

Objective: The present study demonstrates the antidepressant-like effects of Betulin, a natural compound, across multiple behavioral paradigms in mice, including the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Material and Method Reagents and Chemicals Used in the Study: The study utilized high-purity reagents and chemicals for sample preparation, behavioral testing, and biochemical analysis. Standardized Betulin (90% purity, Code: B 1724) was procured from Ottokemi Pvt. Ltd. (Mumbai, India). Sample Preparation: Standardized Betulin (90%), Code: B 1724, was purchased from Ottokemi Pvt. Ltd., located at No. 603, 6th Floor, Tardeo AC Market Building, 87, Tardeo Road, Mumbai-400 034, India (Bharat). The Betulin sample was used in its 90% pure form for the preparation of stock solutions and subsequent animal testing to assess antidepressant activity Dose administration: The required volumes for each group were calculated based on the weight of the animals and the intended doses. For Group 1 (50 mg/kg), 1.5 mL of the solution was withdrawn to administer 250 μL per mouse. Similarly, for Group 2 (100 mg/kg), 3.0 mL of the solution was withdrawn to inject 500 μL per mouse, and for Group 3 (200 mg/kg), 6.0 mL of the solution was used to inject 1000 μL per mouse. The injections were administered intraperitoneally for 21 days to the respective mice in each group, based on the required dose per mouse Result and Discussion: The results from the FST and TST revealed that Betulin administration significantly reduced immobility time in a dose-dependent manner. The highest dose (200 mg/kg) of Betulin produced the most robust antidepressant-like effect. Neurochemical analysis of whole-brain tissue revealed significant, dose-dependent increases in serotonin, dopamine, and norepinephrine levels following Betulin administration. The highest dose (200 mg/kg) produced the most pronounced increases in all three neurotransmitters. Summary and Conclussion: The present study systematically evaluated the antidepressant-like effects of Betulin in murine models, demonstrating its efficacy through behavioral and neurochemical analyses. In the forced swim test (FST) and tail suspension test (TST), Betulin administration significantly reduced immobility time in a dose-dependent manner, with the highest dose (200 mg/kg) showing comparable effects to the reference antidepressants imipramine and desipramine.