Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression. (31st December 2023)

• Record Type: Journal Article
• Authors: Ji-hong, Yuan; Yu, Ma; Ling-hong, Yuan; Jing-jing, Gong; Ling-li, Xu; Lv, Wang; Yong-mei, Jin
• Is Part Of: Pharmaceutical biology. Volume 61:Number 1(2023)
• Page Start: 288
• Page End: 297
• Publication Date: 2023-12-31
• Subjects: TGF-β1 -- idiopathic pulmonary fibrosis -- Smad; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2022.2160767
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context: Fibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF. Objective: This study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence. Materials and methods: Institute of Cancer Research (ICR) mice were randomly assigned to control, bleomycin (BLM), baicalein and BLM + baicalein groups. Lung fibrosis was established by a single intratracheal dose of BLM (3 mg/kg). The baicalein group received baicalein orally (100 mg/kg/day). Sirtuin 3 (Sirt3) siRNA (50 μg) was injected through the tail vein once a week for 2 weeks to explore its effect on the anti-pulmonary fibrosis of baicalein. Results: BLM-treated mice exhibited obvious lung fibrosis and fibroblast senescence by showing increased levels of collagen deposition (27.29% vs. 4.14%), hydroxyproline (208.05 vs. 40.16 ng/mg), collagen I (25.18 vs. 9.15 μg/mg), p53, p21, p16, MCP-1, PAI-1, TNF-α, MMP-10 and MMP-12 in lung tissues, which were attenuated by baicalein. Baicalein also mitigated BLM-mediated activation of TGF-β1/Smad signalling pathway. Baicalein restored the BLM-induced downregulation of Sirt3 expression in lung tissues and silencing of Sirt3 abolished the inhibitory role of baicalein against BLM-induced lung fibrosis, fibroblast senescence and activation of TGF-β1/Smad signalling pathway. Conclusions: Baicalein preserved the BLM-induced downregulation of lung Sirt3 expression, and thus the suppression of TGF-β1/Smad signalling pathway and lung fibrosis, which might provide an experimental basis for treatment of IPF.