Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Salah Salim St., Beni-Suef, 62514, Egypt.
Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Inflammation. 2019 Jun;42(3):1103-1116. doi: 10.1007/s10753-019-00973-8.
Umbelliferone (UMB) is a natural coumarin that has diverse biological activities. However, its potential to protect against liver fibrosis has not been reported yet. This study aimed to investigate the protective effect of UMB against carbon tetrachloride (CCl)-induced liver fibrosis in rats. Rats received CCl and UMB for 8 weeks and samples were collected for analyses. CCl induced a significant increase in serum levels of liver function markers and pro-inflammatory cytokines. Treatment with UMB significantly ameliorated liver function markers and pro-inflammatory cytokines and prevented CCl-induced histological alterations. CCl promoted significant upregulation of α-smooth muscle actin (SMA), collagen I, collagen III, NF-κB p65, TGF-β1, and p-Smad3. Masson's trichrome staining revealed a significant fibrogenesis in CCl-induced rats. Treatment with UMB suppressed TGF-β1/Smad3 signaling and downregulated α-SMA, collagen I, collagen III, and NF-κB p65. In addition, UMB diminished malondialdehyde and nitric oxide levels, boosted reduced glutathione and antioxidant enzymes, and upregulated the expression of PPARγ. In conclusion, our results demonstrated that UMB prevented CCl-induced liver fibrosis by attenuating oxidative stress, inflammation, and TGF-β1/Smad3 signaling, and upregulating PPARγ. Therefore, UMB may be a promising candidate for preventing hepatic fibrogenesis, given that further research is needed to delineate the exact molecular mechanisms underlying its antifibrotic efficacy.
香豆素（UMB）是一种天然香豆素，具有多种生物活性。然而，其预防肝纤维化的潜力尚未被报道。本研究旨在探讨 UMB 对四氯化碳（CCl）诱导的大鼠肝纤维化的保护作用。大鼠接受 CCl 和 UMB 治疗 8 周后收集样本进行分析。CCl 导致血清肝功能标志物和促炎细胞因子水平显著升高。UMB 治疗可显著改善肝功能标志物和促炎细胞因子，并预防 CCl 诱导的组织学改变。CCl 促进α-平滑肌肌动蛋白（α-SMA）、I 型胶原、III 型胶原、NF-κB p65、TGF-β1 和 p-Smad3 的显著上调。Masson 三色染色显示 CCl 诱导的大鼠有明显的纤维化。UMB 抑制 TGF-β1/Smad3 信号通路，并下调α-SMA、I 型胶原、III 型胶原和 NF-κB p65。此外，UMB 降低丙二醛和一氧化氮水平，增加还原型谷胱甘肽和抗氧化酶，并上调 PPARγ 的表达。总之，我们的结果表明，UMB 通过减轻氧化应激、炎症和 TGF-β1/Smad3 信号通路以及上调 PPARγ 来预防 CCl 诱导的肝纤维化。因此，鉴于需要进一步研究来阐明其抗纤维化功效的确切分子机制，UMB 可能是预防肝纤维化的有前途的候选药物。
