Deng Kaili, Li Min, Xiang Liangliang, Wang Yuhua, Li Yamei, Wen Junya, Li Yuanyuan, Kuang Shanshan, Wen Jinjie, Zhou Chuying, Huang Sha, Lv Zhiping
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
Auckland Bioengineering Institute, The University of Auckland, Auckland, 1010, New Zealand.
Phytomedicine. 2025 Feb;137:156363. doi: 10.1016/j.phymed.2025.156363. Epub 2025 Jan 2.
Early intervention in hepatic fibrosis (HF) is critical to reducing the risk of cirrhosis-related mortality and hepatocellular cancer. However, treating fibrosis has proven to be more challenging, with no approved anti-fibrotic therapies currently available for HF. Traditional Chinese medicines (TCMs) hold significant potential for the management of HF.
This study aims to propose a systematic approach for investigating the pharmacological basis of Baoganning (BGN) Decoction, providing empirical evidence to support future research on its targets and mechanisms of BGN.
Ultrahigh-performance liquid chromatography coupled with high- resolution mass spectrometry (UPLC-HRMS) was employed to analyze the chemical composition of BGN. Key compounds were investigated using disease databases to predict relevant targets, followed by molecular docking and molecular dynamics simulations to explore molecular-level interactions. The efficacy and critical targets of BGN were validated through in vivo and in vitro experiments.
UPLC-HRMS was used to identify the chemical composition of the BGN, and serum pharmacology determined the active chemical constituents in rat plasma. Zebrafish, HSC-T6 cells, JS-1 cell line and mice served as experimental models to evaluate the antifibrotic effects of BGN.
BGN demonstrated significant antifibrotic effect in vivo and in vitro models. A total of 757 compounds were identified in BGN, with 18 prototypical components and metabolites detected. Three compounds-quillaic acid, methyl cholate, and 3β-hydroxy-5-cholenoic exhibited dose-dependent inhibitory effects on HF. Molecular docking studies revealed stable interactions between these compounds and predicted targets. Additionally, the screened components effectively reduced the expression of α-SMA and COL-I in both a cellular model and a zebrafish fibrosis model in a dose-dependent manner.
The comprehensive analysis of BGN's chemical composition and its metabolic processes provides valuable insights into its pharmacological effects. These findings support the potential clinical and international application of BGN in treating hepatic fibrosis and improving patient outcomes.
肝纤维化（HF）的早期干预对于降低肝硬化相关死亡率和肝细胞癌风险至关重要。然而，事实证明治疗纤维化更具挑战性，目前尚无批准用于HF的抗纤维化疗法。中药在HF管理方面具有巨大潜力。
本研究旨在提出一种系统方法来研究保肝宁（BGN）汤的药理基础，为未来对BGN的靶点和作用机制的研究提供实证依据。
采用超高效液相色谱-高分辨率质谱联用（UPLC-HRMS）分析BGN的化学成分。利用疾病数据库研究关键化合物以预测相关靶点，随后通过分子对接和分子动力学模拟探索分子水平的相互作用。通过体内和体外实验验证BGN的疗效和关键靶点。
采用UPLC-HRMS鉴定BGN的化学成分，血清药理学确定大鼠血浆中的活性化学成分。斑马鱼、HSC-T6细胞、JS-1细胞系和小鼠作为实验模型评估BGN的抗纤维化作用。
BGN在体内和体外模型中均表现出显著的抗纤维化作用。在BGN中总共鉴定出757种化合物，检测到18种原型成分和代谢产物。三种化合物——齐墩果酸、胆酸甲酯和3β-羟基-5-胆烯酸对HF表现出剂量依赖性抑制作用。分子对接研究揭示了这些化合物与预测靶点之间的稳定相互作用。此外，筛选出的成分在细胞模型和斑马鱼纤维化模型中均以剂量依赖性方式有效降低α-SMA和COL-I的表达。
对BGN化学成分及其代谢过程的综合分析为其药理作用提供了有价值的见解。这些发现支持BGN在治疗肝纤维化和改善患者预后方面的潜在临床和国际应用。
