Yang Lu, Bao Yuchen, Fu Qinwen, Fu Yue, Tian Qingqing, Tang Yu, Xia Zihan, Zhou Huifang, Wu Chuyue, Sun Jilin, Huang Qinwan
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Sichuan Fuzheng Pharmaceutical Co., Ltd., Sichua, China.
Comb Chem High Throughput Screen. 2025;28(7):1153-1169. doi: 10.2174/0113862073278353231226100219.
ALD is a chronic liver disease caused by chronic excessive alcohol consumption, for which there are no drugs with better efficacy. Ancient literature and modern studies have shown that Massa Medicata Fermentata (MMF) has a hangover effect and ameliorates hepatic inflammation, so we believe that MMF has a potential role in the treatment of alcoholic liver disease.
UPLC-Q-Orbitrap HRMS was used to characterize the chemical constituents in MMF. The database was utilized to collect targets for the components and diseases, and cross-targeting analysis of the targets was performed. PPI, KEGG, GO enrichment analysis and molecular docking were performed using the core cross-targeting information to preliminarily validate the mechanism of action of MMF on disease. Finally, animal validation was carried out using male KM mice of the alcoholic liver injury model.
MMF could play a role in the therapeutic prevention of alcoholic liver disease through the core targets AKT1, TNF, TP53, IL6 and CASP3 to regulate cancer pathways, lipid, and atherosclerosis, targeting IL-17 signaling, TNF signaling pathway, and hepatitis C, which was confirmed by animal pharmacodynamic experiments.
This study serves as a rationale to support MMF in the treatment of ALD and meets the urgent need for clinical treatment of ALD. At the same time, it broadens the scope of clinical application of MMF.
酒精性肝病(ALD)是一种由长期过量饮酒引起的慢性肝病,目前尚无疗效更佳的药物。古代文献和现代研究表明,六神曲具有解酒作用并能减轻肝脏炎症,因此我们认为六神曲在酒精性肝病的治疗中具有潜在作用。
采用超高效液相色谱-四极杆-轨道阱高分辨质谱(UPLC-Q-Orbitrap HRMS)对六神曲中的化学成分进行表征。利用数据库收集成分和疾病的靶点,并对靶点进行交叉靶向分析。使用核心交叉靶向信息进行蛋白质-蛋白质相互作用(PPI)、京都基因与基因组百科全书(KEGG)、基因本体(GO)富集分析和分子对接,以初步验证六神曲对疾病的作用机制。最后,使用酒精性肝损伤模型的雄性昆明(KM)小鼠进行动物验证。
六神曲可通过核心靶点蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)、白细胞介素6(IL6)和半胱天冬酶3(CASP3)在酒精性肝病的治疗预防中发挥作用,调节癌症通路、脂质和动脉粥样硬化,靶向白细胞介素-17信号通路、肿瘤坏死因子信号通路和丙型肝炎,动物药效学实验证实了这一点。
本研究为支持六神曲治疗酒精性肝病提供了理论依据,满足了酒精性肝病临床治疗的迫切需求。同时,拓宽了六神曲的临床应用范围。