Liang Lijuan, Dong Zhiheng, Shen Ziqing, Zang Yifan, Yang Wenlong, Wu Lan, Bao Lidao
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.
Mol Med Rep. 2025 Jul;32(1). doi: 10.3892/mmr.2025.13536. Epub 2025 Apr 17.
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 (CCl) was injected intraperitoneally to induce HF in rats and primary HSCs were treated 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. , 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.
肝纤维化（HF）是晚期慢性肝病的关键标志物，肝星状细胞（HSCs）在其中起关键作用。目前，尚无有效的HF治疗方法。伞形酮（7-羟基香豆素；UMB）是一种具有显著抗炎、抗氧化和抗肿瘤活性的天然化合物。然而，其在治疗HF方面的潜在疗效尚未得到研究。本研究探讨了UMB对HF的保护作用，靶向转化生长因子-β1-Smad信号通路以探究UMB的潜在作用机制。腹腔注射四氯化碳（CCl）诱导大鼠肝纤维化，并使用UMB处理原代HSCs，以研究UMB对肝纤维化的改善作用。采用苏木精-伊红染色、酶联免疫吸附测定、逆转录-定量PCR、细胞计数试剂盒-8和蛋白质印迹法检测大鼠肝组织和HSCs中纤维化标志物、炎症、氧化应激及转化生长因子-β1-Smad信号通路的水平。肝组织病理学、肝功能指标和纤维化标志物的改善表明，UMB显著抑制了CCl4诱导的大鼠肝纤维化和炎症。此外，UMB显著降低了促炎因子和氧化应激水平。UMB还显著抑制了原代HSC的激活，并降低了α-平滑肌肌动蛋白和I型胶原蛋白的表达。机制实验证明，UMB抑制了转化生长因子-β1-Smad信号通路并改善了肝纤维化。据作者所知，本研究首次证明UMB可能是一种有前途的治疗肝纤维化的天然活性化合物。其治疗效果与其对转化生长因子-β1-Smad信号通路的调节有关。
