AUTHOR=Du Qiaohui , Gao Chong , Tsoi Bun , Wu Meiling , Shen Jiangang 

TITLE=Niuhuang Qingxin Wan ameliorates depressive-like behaviors and improves hippocampal neurogenesis through modulating TrkB/ERK/CREB signaling pathway in chronic restraint stress or corticosterone challenge mice

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1274343

DOI=10.3389/fphar.2023.1274343

ISSN=1663-9812

ABSTRACT=Chronic stress associated hormonal imbalance impairs hippocampal neurogenesis, contributing to depressive and anxiety behaviors. Targeting neurogenesis becomes a promising antidepressant therapeutic strategy. Niuhuang Qingxin Wan (NHQXW) is a herbal formula for mental disorders in Traditional Chinese Medicine (TCM) practice, but its anti-depressant efficacies and mechanisms remain unverified. In the present study, we tested the hypothesis that NHQXW could ameliorate depressive-like behaviors and improves hippocampal neurogenesis through modulating TrkB/ERK/CREB signaling pathway by utlizing two depressant mouse models including chronic restraint stress (CRS) mouse model and chronic corticosterone (CORT) stress (CCS) induced mouse model. NHQXW was orally treated to the depression like mouse models whereas fluoxetine was used as positive control group.We evaluated the effects of NHQXW on depressive-and anxiety-like behaviors and determined the effects of NHQXW on inducing hippocampal neuorogenesis. NHQXW treatment significantly ameliorated depressive-like behaviors in those chronic stress mouse models. NHQXW significantly improved hippocampal neurogenesis in the CRS mice and CCS mice. The potential neurogenic mechanism of NHQXW was identified through regulating the expression levels of BDNF, TrkB, p-ERK (T202/T204), p-MEK1/2 (S217/221) and p-CREB (S133) in the hippocampus area of the CCS mice.NHQXW revealed its antidepressant and neurogenic effects that were similar with fluoxetine. Moreover, NHQXW treatment revealed long term effects on preventing the withdrawal associated rebound symptoms in the CCS mice. Furthermore, in bioactivityguided quality control study, Liquiritin was identified as one of the bioactive compounds of NHQXW with the bioactivities of neurogenesis-promoting effects.Taken together, NHQXW could be a promising TCM formula to attenuate the depressive and anxiety like behaviors against chronic stress and depression. The underlying anti-depressant mechanisms could be correlated with its neurogenic activities by stimulating TrkB/ERK/CREB signaling pathway.