基于指纹图谱、网络药理学和定量分析的南五味子治疗药源性肝损伤的质量标志物研究  

Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology,fingerprint and quantitative analysis

作　　者：林路洁 张明晓 李化[1] 兰雪梅 魏晓露[1] 郭丛[1] 杨滨[1] LIN Lu-jie;ZHANG Ming-xiao;LI Hua;LAN Xue-mei;WEI Xiao-lu;GUO Cong;YANG Bin(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Southwestern University,Chongqing 400715,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]西南大学,重庆400715

出　　处：《中国中药杂志》2023年第20期5460-5473,共14页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82173964);中央级公益性科研院所基本科研业务费专项(ZXKT20021,ZXKT17065)。

摘　　要：根据中药质量标志物(Q-marker)的理念,采用超高效液相色谱法(UPLC)建立指纹图谱和多指标定量的方法,结合网络药理学研究,筛选南五味子保肝功效的潜在质量标志物。采用《中药色谱指纹图谱相似度评价系统》软件对15批不同产地的南五味子指纹图谱进行相似度分析,相似度在0.981~0.998。确定了18个共有成分,由聚类分析和主成分分析确定了3个差异性成分;构建“成分-靶点-通路”网络图,预测南五味子保肝的核心成分,筛选出14个与南五味子治疗药源性肝损伤(drug-induced liver injury,DILI)作用相关的核心成分,通过作用于AKT1、CCND1、CYP1A1、CYP3A4、MAPK1、MAPK3、NOS2、NQO1、PTGS2等靶点,调控脂质和动脉粥样硬化、乙型肝炎、白细胞介素-17、肿瘤坏死因子等信号通路发挥保肝作用。结合成分的可测性、特有性、有效性,预测五味子酯甲、安五脂素和五味子甲素是南五味子治疗DILI的质量标志物。15批样品中五味子酯甲、安五脂素和五味子甲素的质量分数分别为0.20%~0.57%、0.13%~0.33%、0.42%~0.70%。综上,该研究综合利用指纹图谱、网络药理学、含量测定等多技术的融合策略,科学合理地推测了南五味子治疗DILI的质量标志物,可为提升南五味子的质量评价标准、探索南五味子治疗DILI的作用机制提供依据。This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology.The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System,which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998.Eighteen common components were identified,from which 3 differential components were selected by cluster analysis and principal component analysis.The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects.Fourteen core components were screened by network pharmacology.They acted on the targets such as AKT1,CCND1,CYP1A1,CYP3A4,MAPK1,MAPK3,NOS2,NQO1,and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis,hepatitis B,interleukin-17,and tumor necrosis factor.Considering the chemical measurability,characteristics,and validity,schisantherin A,anwulignan,and schisandrin A were identified as the Q-markers.The content of schisantherin A,anwulignan,and schisandrin A in the test samples were 0.20%-0.57%,0.13%-0.33%,and 0.42%-0.70%,respectively.Combining the fingerprint,network pharmacology,and content determination,this study predicted that schisantherin A,anwulignan,and schisandrin A were the Q-markers for the hepatoprotective effect of SSF.The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.

关 键 词：南五味子 药源性肝损伤 指纹图谱 网络药理学 质量标志物 

分 类 号：R285[医药卫生—中药学] R284.1[医药卫生—中医学]