基于肝脂调控和肝毒性的大黄蒽醌机制研究进展  

Research Progress in Mechanisms of Rhubarb Anthraquinone Based on Hepatic Lipid Regulation and Hepatotoxicity

作　　者：刘颖 宋绪钰 孙蓉 LIU Ying;SONG Xuyu;SUN Rong(Academy of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan Shandong 250033,China;Department of Orthopaedic Trauma Surgery,the Second Hospital of Shandong University,Jinan Shandong 250033,China;Advanced Medical Research Institute,Shandong University,Jinan Shandong 250012,China)

机构地区：[1]天津中医药大学中医药研究院,天津301617 [2]山东大学第二医院基础医学研究所,山东济南250033 [3]山东大学第二医院创伤骨科,山东济南250033 [4]山东大学高等医学研究院,山东济南250012

出　　处：《中国药物警戒》2024年第12期1432-1440,共9页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2022YFC3502100);国家重点研发计划课题五(2022YFC3502105)。

摘　　要：目的针对肝脂代谢异常疾病,细分大黄的效-毒物质基础,对大黄蒽醌的肝脂调控及其肝毒性机制进行综述,以期为治疗肝脂代谢异常疾病提供参考。方法通过检索建库至2024年9月5日使用中国知网、PubMed、Web of Science、Wiley、Google scholar等数据库,对各数据库所收录近10年内发表的有关大黄蒽醌调控肝脂及其导致肝毒性相关文献进行检索,并对其作用机制进行整理和总结。结果大黄蒽醌中的大黄素、大黄酸、大黄酚、芦荟大黄素、大黄素甲醚为大黄调控肝脂的物质基础,其作用机制主要与降低细胞外基质(Extracellular Matrix,ECM)相关I型胶原蛋白、α-平滑肌肌动蛋白(α-Smooth Muscle Actin,α-SMA)的表达、抑制肝纤维化,降低丙二醛(Malondialdehyde,MDA)、细胞内活性氧(Reactive Oxygen Species,ROS)表达水平、抑制肝脏氧化,降低白细胞介素-1α(Interleukin-1α,IL-1α)、肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)等炎症介质的表达、减轻肝脏炎症等相关。同时,蒽醌类化合物的肝毒性作用机制主要与改变线粒体膜电位、破坏氧化磷酸化通路;增加ROS水平、引起细胞内氧化应激;引起胆红素代谢异常等相关。结论大黄蒽醌类化合物通过多成分、多靶点、多途径来调控肝脂代谢和诱发肝毒性。因此,应进一步探究大黄蒽醌类化合物在改善肝脂代谢相关疾病中的安全剂量范围,尽量减少潜在风险,以期优化其临床应用并获得更广泛的应用前景。Objective To review the efficacy and toxicity material basis of rhubarb,especially the regulation of liver lipids by rhubarb anthraquinones,and the mechanisms of hepatotoxicity in order to facilitate the treatment of liver lipid metabolism disorders.Methods Literature published over the past 10 years(as of September 5,2024)was retrieved from such databases as CNKI,PubMed,Web of Science,Wiley and Google scholar.Studies related to the regulation of liver lipids and hepatotoxicity induced by rhubarb anthraquinones were analyzed,and the mechanisms of action were summarized.Results The main anthraquinone compounds in rhubarb that regulated liver lipids included emodin,chrysophanol,aloeemodin,and physcion.The mechanisms of action involved reducing the expressions of extracellular matrix(ECM)-related proteins such as type I collagen and a-smooth muscle actin(α-SMA)inhibiting liver fibrosis,reducing malondialdehyde(MDA)and reactive oxygen species(ROS)levels,and mitigating hepatic oxidative stress.Additionally,these anthraquinone compounds could reduce the expressions of inflammatory mediators,including interleukin-1α(IL-1α)and tumor necrosis factor-α(TNF-α)while alleviating liver inflammation.Meanwhile,the hepatotoxicity of anthraquinones was primarily linked to changes in mitochondrial membrane potential,disruption of oxidative phosphorylation,increased intracellular ROS,induction of oxidative stress,and abnormalities in bilirubin metabolism.Conclusion Rhubarb anthraquinones can regulate liver lipid metabolism and induce hepatotoxicity via multi-component,multi-target,and multi-pathway actions.More research is needed to determine the range of safe dosage,minimize risks,and optimize clinical applications for the treatment of liver lipid metabolism disorders.

关 键 词：大黄素 大黄酸 芦荟大黄素 大黄酚 大黄素甲醚 肝脂调控 肝毒性 作用机制 

分 类 号：R994.11[医药卫生—毒理学] R977[医药卫生—药学]