Antidepressant Potential of Hispidulin Present in S. barbata D. Don: Mechanistic Insights through Neurochemical and Behavioral Assessments

Background and Aim: This study aims to investigate the antidepressant properties of Hispidulin, a flavonoid present in Scutellaria barbata D. Don. The selection of Hispidulin stems from its notable inhibitory activity against Xanthine Oxidase (XO), a parameter in the pathophysiology of depression. Material and Methods: Mice were subjected to a rigorous evaluation using a murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression for 21 days and antidepressant properties were rigorously assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Imipramine and fluoxetine were used as standard drugs. Additionally, neurochemical analyses were conducted to quantify serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels in the cortex, hippocampus, and hypothalamus. Further mechanistic insights were sought through the estimation of monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in the brain. Plasma nitrite and corticosterone levels were also measured to delineate the underlying mechanism of action. Results: Hispidulin demonstrated significant antidepressant effects, as evidenced by reduced immobility time in TST and FST and increased exploratory behavior in OFT. Neurochemical analysis revealed restoration of 5-HT, NE, and DA levels in key brain regions. Furthermore, Hispidulin modulated MAO activity and enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were elevated, indicating enhanced nitric oxide synthesis, while corticosterone levels were reduced. Conclusion: Our findings indicate that Hispidulin exerts potent antidepressant effects, potentially mediated through its influence on monoaminergic neurotransmitters, MAO activity, and antioxidant defenses. These results provide valuable mechanistic insights into the antidepressant action of Hispidulin, supporting its potential therapeutic application in depressive disorders.