Inhibitory effects of umbelliferone on carbon tetrachloride-induced hepatic fibrosis in rats through the TGF‑&beta;1‑Smad signaling pathway

Liang,Lijuan; Dong,Zhiheng; Shen,Ziqing; Zang,Yifan; Yang,Wenlong; Wu,Lan; Bao,Lidao

doi:10.3892/mmr.2025.13536

Inhibitory effects of umbelliferone on carbon tetrachloride-induced hepatic fibrosis in rats through the TGF‑β1‑Smad signaling pathway

Authors:
- Lijuan Liang
- Zhiheng Dong
- Ziqing Shen
- Yifan Zang
- Wenlong Yang
- Lan Wu
- Lidao Bao
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Affiliations: College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China, Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010030, P.R. China, Mongolia Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China, Department of Pharmacy, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region 010030, P.R. China
Published online on: April 14, 2025 https://doi.org/10.3892/mmr.2025.13536
Article Number: 171
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatic fibrosis (HF) is a critical marker of advanced‑stage chronic liver disease and involves pivotal contributions from hepatic stellate cells (HSCs). Currently, there are no effective treatments for HF. Umbelliferone (7‑hydroxycoumarin; UMB) is a natural compound with significant anti‑inflammatory, antioxidant and anti‑tumor activities. However, its potential efficacy in treating HF has not been studied. The present study explored the protective effects of UMB against HF, targeting the TGF‑β1‑Smad signaling pathway to explore the underlying mechanisms of UMB. Carbon tetrachloride (CCl₄) was injected intraperitoneally to induce HF in rats and primary HSCs were treated in vitro with UMB to investigate the improvement effect of UMB on HF. The levels of fibrosis markers, inflammation, oxidative stress and TGF‑β1‑Smad signaling pathway in the rat liver tissue and HSCs were detected using hematoxylin and eosin staining, enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR, Cell Counting Kit‑8 and western blotting. The improvement in liver histopathology, liver function indexes and fibrosis markers demonstrated that UMB markedly inhibited the CCl4‑induced HF and inflammation in the rats. Additionally, UMB prominently reduced the pro‑inflammatory factors and oxidative stress levels. In vitro, UMB markedly inhibited primary HSC activation and decreased alpha‑smooth muscle actin and collagen I expression. The mechanism experiment proved that UMB inhibited the TGF‑β1‑Smad signaling pathway and ameliorated HF. The present study was the first to demonstrate, to the best of the authors' knowledge, that UMB might be a promising natural active compound for treating HF. Its therapeutic effect is associated with its modulation of the TGF‑β1‑Smad signaling pathway.

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