Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China; School of Pharmacy, Jinan University, Guangzhou, 510632, PR China.
School of Pharmacy, Guangdong Medical University, Dongguan, 523808, PR China.
J Ethnopharmacol. 2024 Nov 15;334:118557. doi: 10.1016/j.jep.2024.118557. Epub 2024 Jul 14.
Ficus hirta Vahl., a traditional Chinese medicine commonly used in the Lingnan region, has been extensively used for liver disease treatment in China. Its notable antioxidant and anti-inflammatory properties have been reported in previous studies. However, its potential effect and underlying mechanism on liver fibrosis remains unclear.
This study was aimed to investigate the effect and its underlying mechanism of Ficus hirta Vahl on liver fibrosis in vitro and in vivo.
The main components of Ficus hirta Vahl in blood were investigated by using UPLC-Q/TOF-MS/MS. Two animal models of liver fibrosis, the CCl and MCD induced mice, were used to assess the efficacy of Ficus hirta Vahl on liver fibrosis. Metabolomics was used to detect the level of metabolites in the serum of liver fibrosis mice after Ficus hirta Vahl treatment. Furthermore, the mechanism was validated in vitro using the human liver stellate cell line LX-2. The binding affinities of the active ingredients of Ficus hirta Vahl to the main targets of liver fibrosis were also determined. Finally, we identified the key active ingredients responsible for the treatment of liver fibrosis in vivo.
Fibrosis and inflammatory markers were significant down-regulation in both CCl and MCD induced liver fibrosis mice after Ficus hirta Vahl administration in a dose-dependent manner. We found that Ficus hirta Vahl may primarily exert its effect on liver fibrosis through the glutathione metabolic pathway. Importantly, the glutathione metabolic pathway is closely associated with ferroptosis, and our subsequent in vitro experiments provided evidence supporting this association. Ficus hirta Vahl was found to modulate the GSH/GPX4 pathway, ultimately leading to the amelioration of liver fibrosis. Moreover, using serum pharmacochemistry and molecular docking, we successfully identified apigenin as a probable efficacious monomer for the management of liver fibrosis and subsequently validated its efficacy in mice with CCl-induced hepatic fibrosis.
Ficus hirta Vahl triggered the ferroptosis of hepatic stellate cell by regulating the GSH/GPX4 pathway, thereby alleviating liver fibrosis in mice. Moreover, apigenin is a key compound in Ficus hirta Vahl responsible for the effective treatment of liver fibrosis.
榕树叶，一种在中国岭南地区广泛应用的传统中药，已被广泛用于治疗肝脏疾病。先前的研究报道了其显著的抗氧化和抗炎特性。然而，其对肝纤维化的潜在作用和机制尚不清楚。
本研究旨在探讨榕树叶对体内外肝纤维化的作用及其潜在机制。
采用 UPLC-Q/TOF-MS/MS 研究榕树叶的主要血液成分。采用 CCl 和 MCD 诱导的小鼠两种肝纤维化动物模型，评估榕树叶对肝纤维化的疗效。代谢组学用于检测榕树叶处理后肝纤维化小鼠血清中的代谢物水平。此外，在人肝星状细胞系 LX-2 中进行体外验证。还测定了榕树叶的活性成分与肝纤维化主要靶点的结合亲和力。最后，我们在体内鉴定了负责治疗肝纤维化的关键活性成分。
榕树叶在剂量依赖性的方式下，可显著下调 CCl 和 MCD 诱导的肝纤维化小鼠的纤维化和炎症标志物。我们发现榕树叶可能主要通过谷胱甘肽代谢途径发挥其对肝纤维化的作用。重要的是，谷胱甘肽代谢途径与铁死亡密切相关，我们随后的体外实验提供了支持这一关联的证据。榕树叶被发现调节 GSH/GPX4 途径，最终改善肝纤维化。此外，采用血清药理学和分子对接，我们成功鉴定出芹菜素是一种可能有效的单体，用于管理肝纤维化，并随后在 CCl 诱导的肝纤维化小鼠中验证了其疗效。
榕树叶通过调节 GSH/GPX4 途径触发肝星状细胞的铁死亡，从而减轻小鼠的肝纤维化。此外，芹菜素是榕树叶中负责有效治疗肝纤维化的关键化合物。
