title: Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways.
abstract: Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS. In total, 24 male Wistar rats were randomly divided into three groups, including control (n=8, no treatment), induced with chronic unpredictable mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for cell survival and proliferation assays. In KXS rats, increased protein expression levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the hippocampus and prefrontal cortex, compared with the CMS model group. Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3β were also detected in the hippocampus and prefrontal cortex of KXS-treated rats compared with CMS model rats and in primary hippocampal neuronal cells treated with KXS. These results suggest that pCREB and upstream components, including TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect induced by KXS. Further studies are required to confirm these findings.
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Xian-Zhe
authors.initials: XZ
authors.lastname: Dong
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Dong-Xiao
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China.
authors.forename: Bing-Ying
authors.initials: BY
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
keywords: Kai-Xin-San; antidepressant effect; brain-derived neurotrophic factor; extracellular signal-regulated kinase signal pathway; traditional Chinese medicinal formula