Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; Sichuan Provincial Engineering Research Center of Innovative Re-development of Famous Classical Formulas, Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Chengdu 611930, China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan, China.
J Ethnopharmacol. 2024 Nov 15;334:118593. doi: 10.1016/j.jep.2024.118593. Epub 2024 Jul 19.
Treatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive.
This study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings.
Tetrachloromethane (CCl) was used to induce hepatic fibrosis in male rats. In vitro, activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo, liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated.
GFW alleviated CCl-induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination.
GFW attenuates Ccl-induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis.
目前，治疗肝纤维化的方法有限，肝纤维化是一种常见的肝脏疾病，与肝硬化密切相关。虽然桂枝茯苓丸（GFW）是一种从中药中提取的药丸，已被报道具有保肝作用，但它在肝纤维化中的治疗效果和机制仍不清楚。
本研究旨在评估 GFW 在体内和体外环境中抗纤维化的影响及其潜在机制。
四氯化碳（CCl）用于诱导雄性大鼠肝纤维化。体外，血小板衍生生长因子-BB（PDGF-BB）激活肝星状细胞（HSCs）。在体内，评估了肝功能、病理改变和 HSC 激活情况。此外，还研究了 GFW 对体外激活的 Lieming Xu-2（LX-2）细胞的影响。网络药理学用于鉴定 GFW 在肝纤维化中的潜在靶点。最后，研究了 GFW 对 HSCs 中 PTEN/AKT/mTOR 通路和 PTEN 泛素化的影响。
GFW 以剂量依赖的方式减轻 CCl 诱导的大鼠肝损伤和瘢痕形成，并抑制体内 HSC 激活。此外，GFW 抑制了体外激活的 HSCs 的增殖、迁移、分化和细胞外基质（ECM）产生。GFW 还促进了 HSCs 的自噬和凋亡。同时，网络药理学和体外研究表明，GFW 通过抑制泛素化来阻止 PTEN 降解，从而抑制 AKT/mTOR 通路。
GFW 通过调节 PTEN/AKT/mTOR 信号通路减轻雄性大鼠 Ccl 诱导的肝纤维化，使其成为治疗肝纤维化的潜在候选药物。
