State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118840. doi: 10.1016/j.jep.2024.118840. Epub 2024 Sep 21.
Alcoholic liver disease (ALD) is a growing public health concern caused by excessive alcohol consumption, but effective treatments are limited. Ge-Zhi-Jie-Jiu decoction (JJY) is a modified traditional Chinese herbal remedy that aims to alleviate ALD. This formula contains various components such as Ge Hua, Ge Gen, Zhi Ju Zi, and other medicinal-food herbs. However, the specific pharmacotherapeutic compounds of JJY and its pharmacological mechanisms remain unclear.
This study aimed to elucidate the molecular mechanism and pharmacodynamic basis of JJY in treating ALD.
UPLC-Q-Orbitrap HRMS, HPLC fingerprinting, and LC-MS techniques were used for the composition identification and quality control of JJY. The pharmacological components and molecular mechanisms of JJY in anti-ALD were then predicted using network pharmacology and molecular docking approaches. Ultimately, an acute alcoholic liver injury mouse model was developed, and the potential mechanisms were verified by hematoxylin-eosin (H&E), Oil Red O, and TUNEL staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking analysis.
The results showed that the main components of JJY are organic acids, flavonoids, and isoflavonoids, in which puerarin, daidzein, glycitein, ononin, quercetin, and tectorigenin can be used as the indicator components of JJY. In addition, JJY might ameliorate ALD through several pathways, including potentially promoting alcohol metabolism via alcohol-metabolizing enzymes, and possibly inhibiting oxidative stress, inflammation and apoptosis via the Nrf2/Keap1/HO-1 and MAPK signaling pathways. Furthermore, JJY may also alleviated hepatic lipid accumulation through the PPARα signaling pathway.
JJY has significant anti-ALD efficacy with multiple mechanisms. This study offers a solid experimental foundation for JJY's development as a medicine with anti-ALD characteristics and elucidates its probable active components.
酒精性肝病 (ALD) 是一种由过量饮酒引起的日益严重的公共卫生问题，但有效的治疗方法有限。葛栀解酒汤 (JJY) 是一种改良的传统中草药方剂，旨在缓解 ALD。该配方含有各种成分，如葛花、葛根、枳椇子和其他药食同源的草药。然而，JJY 的具体药效化合物及其药理机制尚不清楚。
本研究旨在阐明 JJY 治疗 ALD 的分子机制和药效基础。
采用 UPLC-Q-Orbitrap HRMS、HPLC 指纹图谱和 LC-MS 技术对 JJY 的成分进行鉴定和质量控制。然后，采用网络药理学和分子对接方法预测 JJY 抗 ALD 的药理成分和分子机制。最终，建立急性酒精性肝损伤小鼠模型，通过苏木精-伊红 (H&E)、油红 O 和 TUNEL 染色、实时荧光定量 PCR (RT-qPCR)、Western blot (WB) 和分子对接分析验证潜在机制。
结果表明，JJY 的主要成分是有机酸、黄酮类和异黄酮类，其中葛根素、大豆苷、大豆苷元、染料木苷、槲皮素和染料木素可以作为 JJY 的指标成分。此外，JJY 可能通过多种途径改善 ALD，包括通过酒精代谢酶促进酒精代谢，可能通过 Nrf2/Keap1/HO-1 和 MAPK 信号通路抑制氧化应激、炎症和细胞凋亡。此外，JJY 还可能通过 PPARα 信号通路缓解肝脂质堆积。
JJY 具有显著的抗 ALD 疗效，作用机制多样。本研究为 JJY 作为具有抗 ALD 特性的药物的开发提供了坚实的实验基础，并阐明了其可能的活性成分。
