Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats

Abstract

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg–1·day–1; and oral KXS at a dose of 676 mg·kg–1·day–1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg–1·day–1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg–1·day–1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

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];…”

“…Heterogeneity: χ2 = 23.66, df = 12 (P = 0.02); I 2 = 49%, Figure 3D). Six (15.8%) studies (Wang et al, 2007;Dang, 2008;Dong et al, 2013Dong et al, , 2017Yan et al, 2016;Zhang, 2018) that compared KXS with positive drug treatments reported the number of rearing events in the open-field test. There were no significant differences between the experimental groups and the drug groups (P = 0.90; SMD = −0.02, 95% CI [−0.38, 0.34]; Heterogeneity: χ2 = 0.25, df = 5 (P = 1.00); I 2 = 0%, Figure 4A).…”

“…The pooled data showed that there were no differences between the KXS treatment groups and the positive drug groups (P = 0.26; SMD = 0.21, 95% CI [−0.15, 0.56]; Heterogeneity: χ2 =7.10, df = 5 (P = 0.21); I 2 = 30%, Figure 4C). Ten (26.3%) studies (Wang et al, 2007;Dang, 2008;Dang et al, 2009;Dong et al, 2013Dong et al, , 2017Huang et al, 2014;Fonarow, 2016;Yan et al, 2016;Zhang, 2018) reported sucrose consumption or sucrose preference index in the sucrose preference test. There were no significant differences between the KXS treatment groups and the positive drug groups (P = 0.29; SMD = 0.15, 95% CI [−0.13, 0.42]; Heterogeneity: χ2 =8.67, df = 9 (P = 0.47); I 2 = 0%, Figure 4D).…”

Mechanisms of Panax ginseng action as an antidepressant

“…108 It is possible that Rg3 could be used to treat these disorders based on the regulation of BDNF expression, which needs to be further studied. 61 Increases the protein levels of BDNF, NGF and GDNF, as well as the mRNA expressions of Trk receptors [92][93][94] Promotes neurogenesis and synaptogenesis 92,95 Influences the inflammatory processes via reduction of COX-2, IL-2, IL-6, TNF-α levels and increase of IL-10, IFN-γ levels 97 SYG GTS, PTG GTS, PTG Modulates the levels of 5-HT, DA, NE and ACh 99 XD Bupleurum, Scutellaria, Panax ginseng, Pinellia, Ginger, Glycyrrhiza, Jujube…”