Antidepressant Effects of a Plant-Derived Flavonoid Baicalein Involving Extracellular Signal-Regulated Kinases Cascade

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNIF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action.