Antidepressant-like effects of Bupleuri Radix extract

Study aims: Some oriental herbal medicines have been used to treat neuropsychiatric disorders. We found previously that Kami-shoyo-san (KSS) possesses antidepressant-like effects at both the behavioral and molecular levels. Bupleuri Radix (BR), a major component of KSS, has affinity for both dopamine D-2 and 5-HT1A receptors, which may be responsible for its antidepressant-like effects. In the present study, we investigated the antidepressant-like effects of BR in rats using the forced swimming test (FST) and the potential mechanisms of BR action in SH-SY5Y cells. Materials and methods: The immobility time of rats treated with BR extract was measured in the FST. Western blotting was performed to examine the expression of proteins involved in the cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)-mediated signaling pathway, thought to be a major target of antidepressant drug action. Results: BR extract (900 mg/kg) significantly reduced immobility time in the FST. Treatment with BR extract (10, 100 and 1000 mu g/mL) significantly increased CREB phosphorylation and elevated BDNF levels in SH-SY5Y cells. BR extract increased phosphorylation of Akt and glycogen synthase kinase-3 beta (GSK-3 beta). Moreover, BDNF small interfering RNA (siRNA) reduced elevated Akt and GSK-3 beta phosphorylation induced by BR extract. A phosphatidylinositol 3-kinase (PI3K) inhibitor blocked the BR-induced increase in phosphorylated Akt levels. Conclusions: These findings suggest that an aqueous extract of BR can exert antidepressant-like effects in behavioral and molecular assays. These results demonstrate that BR may exert its effects through actions on CREB and BDNF activation, leading to stimulation of the PI3K/Akt/GSK-3 beta signaling pathway. (C) 2012 Elsevier GmbH. All rights reserved.