Erxian Decoction‐induced serum exosomes slowed bone marrow mesenchymal stem cell senescence through mitophagy

Objective Erxian Decoction (EXD) is traditionally employed in the treatment of menopausal syndromes, although its underlying mechanisms remain largely undefined. Given that the senescence of bone marrow mesenchymal stem cells (BMSCs) is intertwined with organismal aging and associated diseases, this...

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Published in:The journal of gene medicine 2024-01, Vol.26 (1), p.e3617-n/a
Main Authors: Huang, Haoqiang, Qian, Yinhua, Feng, Ye, Wang, Yitao, Qian, Pingkang, Xu, Feng, Wang, Qing
Format: Article
Language:English
Subjects:
Animals
BMSC
Disulfides
Drugs, Chinese Herbal
Erxian Decoction
Exosomes - metabolism
Mesenchymal Stem Cells - metabolism
Mitophagy
Osteogenesis
osteogenic differentiation
Rats
senescence
serum exosomes
Thiones
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Summary:Objective Erxian Decoction (EXD) is traditionally employed in the treatment of menopausal syndromes, although its underlying mechanisms remain largely undefined. Given that the senescence of bone marrow mesenchymal stem cells (BMSCs) is intertwined with organismal aging and associated diseases, this study endeavored to elucidate the influence of EXD on aging BMSCs and uncover the mechanisms through which EXD impedes BMSC senescence. Methods Initially, we probed the anti‐senescent mechanisms of EXD on BMSCs via network pharmacology. We subsequently isolated and identified exosomes from the serum of EXD‐fed rats (EXD‐Exos) and administered these to H2O2‐induced aging BMSC. Assays were conducted to assess BMSC senescence indicators and markers pertinent to mitochondrial autophagy. Treatments with mitophagy inhibitors and activators were then employed to substantiate our findings. Results Protein–protein interaction (PPI) network analyses spotlighted AKT1, TP53, TNF, JUN, VEGFA, IL6, CASP3 and EGFR as focal targets. Gene Ontology and Kyoto Encylcopedia of Genes and Genomes pathway analyses underscored oxidative stress, mitophagy and cell proliferation as pivotal processes. Our cellular assays ascertained that EXD‐Exos mitigated H2O2‐induced senescence phenotypes in BMSCs. Moreover, EXD‐Exos ameliorated disrupted mitophagy in BMSCs, as evidenced by enhanced cellular membrane potential and diminished reactive oxygen species levels. Intriguingly, EXD‐Exos also preserved the osteogenic differentiation potential of BMSCs while curtailing their adipogenic propensity. Conclusion Our findings compellingly suggest that EXD counteracts BMSC senescence by fostering mitophagy. Schematic depiction of this work. EXD improved mitophagy to slow BMSC senescence through a serum exosome‐dependent mechanism. Its effects include promoting mitochondrial autophagy by increasing membrane potential and reducing ROS levels, promoting osteogenic differentiation of BMSCs, and inhibiting adipose differentiation of BMSCs.
ISSN:1099-498X
1521-2254
DOI:10.1002/jgm.3617