In vivo and computational investigation of the antidepressant-like activity of boldine from Peumus boldus in mice subjected to chronic unpredictable mild stress.

Boldine, an aporphine alkaloid mainly isolated from the bark and leaves of Peumus boldus, is reported to possess neuroprotective, antioxidant, and nootropic activities. Due to its antioxidant and neuroprotective potential, this study explored the antidepressant-like effects of boldine. Boldine (1.5, 3.0, and 6.0 mg/kg, p.o.) was evaluated for antidepressant-like activity in unstressed and stressed Swiss young male albino mice, while molecular docking (Autodock Vina) and pharmacokinetic predictions (SwissADME) provided mechanistic insights. In stressed mice, boldine significantly decreased the immobility time in the tail suspension test at doses of 1.5 and 3.0 mg/kg (p.o.). It also significantly restored the reduced sucrose preference at doses of 1.5, 3.0, and 6.0 mg/kg (p.o.), indicating significant antidepressant-like activity of boldine in mice subjected to chronic unpredictable mild stress (CUMS). Further, boldine significantly reversed the stress-induced increases in brain thiobarbituric acid-reactive substances (TBARS), plasma nitrite, and corticosterone levels, and increased the levels of reduced glutathione and catalase. Boldine inhibited brain MAOA activity at doses of 1.5 and 3.0 mg/kg (p.o.) in stressed mice. Moreover, the results of in silico studies were also correlated with in vivo antidepressant-like activity of boldine. In conclusion, boldine showed significant antidepressant-like activity in mice subjected to CUMS, by alleviating oxidative stress, decreasing plasma corticosterone levels and altering MAOA enzyme.