Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression.

Content Provider	Europe PMC
Author	Ji-hong, Yuan Yu, Ma Ling-hong, Yuan Jing-jing, Gong Ling-li, Xu Lv, Wang Yong-mei, Jin
Copyright Year	2023
Abstract	ContextFibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF.ObjectiveThis study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence.Materials and methodsInstitute 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.ResultsBLM-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.ConclusionsBaicalein 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.
Page Count	10
ISSN	13880209
Journal	Pharmaceutical Biology
Volume Number	61
PubMed Central reference number	PMC9970214
Issue Number	1
PubMed reference number	36815239
e-ISSN	17445116
DOI	10.1080/13880209.2022.2160767
Language	English
Publisher	Taylor & Francis
Publisher Date	2023-12-01
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Subject Keyword	TGF-β1 idiopathic pulmonary fibrosis Smad
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Pharmacology Complementary and Alternative Medicine Pharmaceutical Science