Zuogui Wan slowed senescence of bone marrow mesenchymal stem cells by suppressing Wnt/β-catenin signaling

Wnt信号通路 间充质干细胞 衰老 干细胞 细胞生物学 生物 老年性骨质疏松症 信号转导 癌症研究 内分泌学 骨质疏松症
作者
Xiaohong Kang,Long Chen,Shu‐Chen Yang,Zhangbin Gong,Haiyan Hu,Zhang Xue-li,Chao Liang,Yanwu Xu
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:294: 115323-115323 被引量:21
标识
DOI:10.1016/j.jep.2022.115323
摘要

In traditional Chinese medicine (TCM), Zuogui Wan (ZGW) is a classical prescription for senile disorders and delay aging. Modern studies show that ZGW promotes central nerve cell regeneration, prevents and cures osteoporosis, enhances the body's antioxidant capacity, regulates the body's immune function, and promotes mesenchymal stem cells (MSCs) proliferation.It has been shown that MSCs aging is closely associated with organism's aging and age-related disorders. The study aimed to define the effects of ZGW on the aging bone marrow mesenchymal stem cells (BMSCs) and to identify the mechanisms of ZGW delaying BMSCs senescence.Network pharmacology analysis combined with GEO data mining, molecular docking and experimental validation were used to evaluate the mechanisms by which ZGW delays MSCs senescence (MSCS). LC-MS was used for quality control analysis of ZGW.PPI network analysis revealed that EGF, TNF, JUN, MMPs, IL-6, MAPK8, and MYC are components of the core PPI network. GO and KEGG analyses revealed that oxidative stress, regulation of response to DNA damage stimuli, and Wnt signaling were significantly enriched. GEO database validation also indicated that Wnt signaling closely correlated with MSCs aging. Molecular docking analysis of the top-13 active components in the "ZGW-Targets-MSCS" network indicated that most components have strong affinity for key proteins in Wnt signaling, suggesting that modulation of Wnt signaling is an important mechanism of ZGW activity against MSCS. Further experimental validation found that ZGW indeed regulates Wnt signaling and suppresses the expression of age-related factors to enhance cell proliferation, ameliorate DNA damage, and reduce senescence-related secretory phenotype (SASP) secretion, thereby maintaining multidirectional differentiation of rat BMSCs. Similar results were obtained using the Wnt inhibitor, XAV-939.Together, our data show that ZGW slows BMSCs aging by suppressing Wnt signaling.
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