School of Pharmacy, Qiqihar Medical University, China.
School of Pharmacy, Qiqihar Medical University, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Oct 15;1209:123416. doi: 10.1016/j.jchromb.2022.123416. Epub 2022 Aug 22.
Hepatic fibrosis (HF) is a kind of chronic epidemic liver disease. Glycyrrhiza Uralensis and Salvia Miltiorrhiza (GUSM), traditional Chinese medicine, has the obvious clinical treatment of liver fibrosis. This study aimed to investigate the mechanisms of GUSM against HF by an integrated strategy combining untargeted metabolomics with network pharmacology. The results showed that GUSM prescription can improve the morphology and structure of liver tissue, inhibit the proliferation of collagen fibers and reducing the inflammatory response of the liver and so on. Endogenous metabolites and HF-related potential biomarkers in serum and urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The metabolic pathways were enriched by MetaboAnalyst. GUSM prescription showed an antifibrotic effect on rats by regulating metabolic pathways, mainly pentose and glucuronate interconversions and arachidonic acid metabolism. Network pharmacology was then applied to find 42 overlapping targets of GUSM-HF. Quercetin was found to be the main active component and STAT3 was the main active target in GUSM prescription. Molecular docking showed high affinities between quercetin and STAT3. Therefore, GUSM has protective effects on HF by regulating the metabolism and different signaling pathways. The work also shows that the metabolomic and network pharmacology methods are promising tools to gain insight into the efficacy and mechanism research of traditional Chinese medicines.
肝纤维化（HF）是一种慢性流行肝病。甘草和丹参（GUSM），作为传统中药，对肝纤维化具有明显的临床治疗作用。本研究旨在通过结合非靶向代谢组学和网络药理学的综合策略，探讨 GUSM 抗 HF 的机制。结果表明，GUSM 处方可以改善肝组织的形态和结构，抑制胶原纤维的增殖，减轻肝脏的炎症反应等。通过超高效液相色谱-四极杆飞行时间质谱联用仪（UPLC-Q-TOF/MS）检测血清和尿液中的内源性代谢物和与 HF 相关的潜在生物标志物。使用 MetaboAnalyst 对代谢途径进行富集。GUSM 处方通过调节代谢途径对大鼠表现出抗纤维化作用，主要涉及戊糖和葡糖醛酸相互转化以及花生四烯酸代谢。然后应用网络药理学寻找 GUSM-HF 的 42 个重叠靶点。槲皮素被发现是 GUSM 处方中的主要活性成分，STAT3 是主要的活性靶点。分子对接显示槲皮素与 STAT3 之间具有高亲和力。因此，GUSM 通过调节代谢和不同的信号通路对 HF 具有保护作用。这项工作还表明，代谢组学和网络药理学方法是深入了解中药功效和机制研究的有前途的工具。
