Ginsenoside Rb1 Relieves Cellular Senescence and Pulmonary Fibrosis by Promoting NRF2/QKI/SMAD7 Axis.

Zheng, Qing; Lei, Feng-Ping; Hui, Shan; Tong, Ming; Liang, Li-Hui

Cellular senescence is an adverse factor in the development of pulmonary fibrosis (PF). Ginsenoside Rb1 has been found to inhibit both cellular senescence and PF. This study aimed to elucidate the molecular mechanisms by which ginsenoside Rb1 regulates cellular senescence and PF. A PF mouse model was established by Bleomycin (BLM) administration, and a cell model of senescence was constructed using MRC-5 cells treated with Adriamycin RD (ARD) administration. Hematoxylin and Eosin (HE) staining and Masson staining were employed to evaluate cellular structure and collagen fiber content. RT-qPCR and western blotting were used to detect mRNA and protein expression of the target genes. Enzyme-linked Immunosorbent Assay (ELISA) was applied to measure the protein concentration of IL-1 β and IL-18. SA- β -gal staining was used to evaluate cellular senescence. Our results show that ginsenoside Rb1 effectively suppressed BLM-induced PF in mice. ARD administration to induce cellular senescence reduced NRF2, QKI, and SMAD7 expression in MRC-5 cells. By inducing NRF2 overexpression, ARD-induced cellular senescence and fibrosis in MRC-5 cells were relieved. Notably, NRF2 knockdown abolished the mitigating effects of ginsenoside Rb1 on ARD-induced cellular senescence and fibrosis in MRC-5 cells. Mechanistically, NRF2 increased SMAD7 mRNA stability through the transcriptional regulation of QKI. As expected, ginsenoside Rb1 alleviated ARD-induced senescence and fibrosis in MRC-5 cells by activating the NRF2/QKI/SMAD7 axis. Therefore, it was found that ginsenoside Rb1 mitigates cellular senescence and fibrosis during PF progression by activating the NRF2/QKI/SMAD7 axis. This study provides a potential therapeutic strategy for the treatment of PF and elucidates its mechanism of action.

BIOLOGICAL models; CARRIER proteins; T-test (Statistics); STATISTICAL significance; CELLULAR aging; HERBAL medicine; MICRORNA; ENZYME-linked immunosorbent assay; CELLULAR signal transduction; REVERSE transcriptase polymerase chain reaction; DESCRIPTIVE statistics; MICE; CELL culture; GENE expression; BLEOMYCIN; GLYCOSIDES; ANIMAL experimentation; DOXORUBICIN; WESTERN immunoblotting; ONE-way analysis of variance; DATA analysis software; PULMONARY fibrosis; NUCLEAR factor E2 related factor; INTERLEUKINS

American Journal of Chinese Medicine, 2024, Vol 52, Issue 8, p2491

0192-415X

Academic Journal

10.1142/S0192415X24500952