Cortex Mori Radicis[Morus Alba L. (Moraceae)] extract alleviates senescence via PI3K/Akt signaling in COPD fibroblasts.

Xiaobo Zeng, Dong-sheng Gao, Furong Zhang

Phytomedicine

Dec 1, 2024

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Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is marked by prolonged exposure to cigarette smoke, which accelerates senescence in lung fibroblasts and contributes to lung fibrosis. Cortex Mori Radicis [Morus albal. (Moraceae)], a traditional Chinese medicinal herb known for its antitussive properties, has emerged as a potential therapeutic agent for COPD. This study aims to elucidate the immunological mechanisms by which Cortex Mori Radicis mitigates COPD progression, utilizing a mouse model and the MRC-5 cell line. METHODS AND RESULTS: COPD mouse models were established through chronic cigarette smoke (CS) exposure, followed by isolation of lung fibroblasts. Senescence markers and inflammatory mediators were assessed in both the isolated cells and the mice. Lung fibroblasts and bleomycin (Bleomycin)-treated MRC-5 cells exhibited elevated expression of senescence markers, including senescence-associated beta-galactosidase activity, p16INK4A, p21, p38 MAPK, and p53, along with increased levels of senescence-associated secretory phenotype (SASP) mRNA, such as IL-6 and IL-8. Treatment with Cortex Mori Radicis significantly attenuated the protein levels of these senescence markers and reduced SASP mRNA expression. Furthermore, integration of transcriptomic data from lung tissues and primary fibroblasts, combined with network pharmacology analysis, indicated that Cortex Mori Radicis inhibits fibroblast senescence via the PI3K/Akt pathway, thereby ameliorating lung pathology in COPD mice. CONCLUSION: Through the application of transcriptomics and network analysis, this study identifies that Cortex Mori Radicis suppresses cigarette smoke-induced senescence in pulmonary tissues and bleomycin (Bleomycin)-exposed MRC-5 cells by targeting the PI3K/Akt signaling pathway. These findings underscore the therapeutic potential of Cortex Mori Radicis as a novel intervention for COPD.