The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR/AMPK/ULK1 pathway

The present study aimed to investigate whether apigenin elicits antidepressant effects in depressant-like mice via the regulation of autophagy. The depressant-like behaviors were established in a chronic restraint stress model. Male BALB/c mice were subjected to restraint stress for 6 h/day for a period of 21 days, and deficits in sucrose preference, tail suspension and forced swim tests were confirmed to be improved following oral apigenin. To investigate the underlining mechanisms, the hippocampal levels of p62 and microtubule-associated protein light chain 3-II/I (LC3-II/I) were measured using western blot analysis. The expression levels of LC3-II/I and p62 indicated that the significantly inhibited autophagy level induced by chronic restraint stress can be increased following apigenin treatment. Similar to the level of autophagy, the expression levels of adenosine monophosphate-activated protein kinase (AMPK) and Unc-51 like autophagy activating kinase-1 were downregulated after chronic restraint stress stimulation and, subsequently upregulated following treatment with apigenin. Conversely, the levels of mammalian target of rapamycin (mTOR) were increased in chronic restraint stress mice and inhibited by apigenin. Collectively, the present findings indicated that apigenin potentially promotes autophagy via the AMPK/mTOR pathway and induces antidepressive effects in chronic restraint stress mice.