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.

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer’s Disease Based on Systems Biology

“…The application of the KXS formula has been retrospected to the Tang dynasty, and the explanation of the basis of its potential pharmacodynamic material could also be achieved by modern analytical techniques [52]. At the small molecule level, the LC-Q-TOF-MS method with high resolution and sensitivity was established to analyze the transitional components of KXS in vivo.…”

Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

“…As an indicator of depression, 9 (23.7%) studies (Wang et al, 2007;Dang, 2008;Dong et al, 2013Dong et al, , 2016Dong et al, , 2017Liu W. W. et al, 2015;Yan et al, 2016;Zhang et al, 2016;Zhang, 2018) reported the number of rearing events in the open-field test. Kaixinsan induced a marked increase in the number of rearing events in the open-field test compared with that in the control group (P = 0.0003; SMD = 0.57, 95% CI [0.26, 0.88]; Heterogeneity: χ2 = 15.39, df = 9 (P = 0.05); I 2 = 48%, Figure 3A).…”

“…The pooled data showed that KXS treatment resulted in a marked drop in the duration of immobility in the forced swimming test compared with that in the control groups (P < 0.00001; SMD=-1.92, 95% CI [−2.38, −1.47]; Heterogeneity: χ2 =9.89, df = 5 (P = 0.08); I 2 = 49%, Figure 3C). Thirteen (34.2%) studies (Wang et al, 2007;Dang, 2008;Dang et al, 2009;Dong et al, 2013Dong et al, , 2016Dong et al, , 2017Huang et al, 2014;Liu W. W. et al, 2015;Fonarow, 2016;Yan et al, 2016;Dou, 2017;Zhang, 2018) evaluated sucrose consumption or sucrose preference index in the sucrose preference test. Treatment with KXS resulted in significantly different sucrose consumption or sucrose preference than that in the control group (P < 0.00001; SMD = 1.67, 95% CI [1.37, 1.97];…”

“…Two (5.3%) studies (Dang et al, 2009; showed that KXS treatment resulted in decreased AchE activity (P < 0.0001; SMD = −1.49, 95% CI [−2.19, −0.78]; Heterogeneity: χ2 = 1.09, df = 1 (P = 0.30); I 2 = 9%, Figure 6C). Six studies in 4 (10.5%) articles (Dang, 2008;Dong et al, 2016;Fonarow, 2016) showed decreased levels of brain-derived neurotrophic factor (BDNF) in response to KXS treatment (P < 0.00001; SMD = 1.48, 95% CI [1.11, 1.86]; Heterogeneity: χ2 = 1.19, df = 6 (P = 0.98); I 2 = 0%, Figure 6D). Ten studies in 6 (15.8%) articles (Wang et al, 2005;Dang et al, 2009;Liu W. W. et al, 2015;Yan et al, 2016) showed increased levels of NE in response to KXS (P < 0.00001; SMD = 2.99, 95% CI [1.99, 4.00]; Heterogeneity: χ2 = 47.15, df = 9 (P < 0.00001); I 2 = 81%, Figure 7A).…”

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Buyang Huanwu Decoction in the treatment of Ischemic Stroke

“…A large number of experimental studies and clinical observations have con rmed that Chinese medicine has unique advantages in treating IS. Various empirical prescriptions, single drugs and active ingredient extracts have been shown clear neuroprotective effects on IS [4][5][6].…”