基于“成分-靶点-通路”桑叶质量标志物的辨识与测定  

Identification and determination of the quality marker of mulberry leaf based on“component-target-pathway”network

作　　者：董壮壮 刘文强 韩立华 赵晓茹 胡城龙 原红霞 DONG Zhuangzhuang;LIU Wenqiang;HAN Lihua;ZHAO Xiaoru;HU Chenglong;YUAN Hongxia(School of Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,China;Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation,Shanxi Universi ty of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]山西中医药大学中药与食品工程学院,山西晋中030619 [2]山西中医药大学基于炎性反应的重大疾病创新药物山西省重点实验室,山西晋中030619

出　　处：《沈阳药科大学学报》2024年第5期571-580,共10页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(82003881);山西省医学科技创新团队(2020TD02);山西中医药大学研究生创新创业教育项目(2022CX023);山西中医药大学2020年度科技创新能力培育计划“山西药茶的研制和开发”项目(2020PY-YC-07)。

摘　　要：目的基于“成分-靶点-通路”预测分析桑叶质量标志物(quality markers,Q-marker)并测定其含量。方法应用高效液相色谱法,建立15批桑叶药材的指纹图谱,对共有峰进行指认并进行相似度评价;通过多元统计分析结合网络药理学方法辨识桑叶质量标志物,且对相关成分进行含量测定。结果15批桑叶药材的指纹图谱共确认了9个共有峰,经对照品指认出6个色谱峰,各桑叶样品的相似度在0.908~0.999内。15批样品经聚类分析聚为两类,采用OPLS-DA以变量投影重要性(variable importance in projection,VIP)值>1为标准筛选出绿原酸、芦丁、异槲皮苷、紫云英苷、隐绿原酸、新绿原酸共6个成分,为潜在的生物标志物。基于网络药理学研究发现该6个成分主要通过T细胞受体信号通路、c型凝集素受体信号通路、MAPK信号通路等发挥降糖降脂、抗炎等作用,可作为桑叶的质量标志物。经测定,桑叶中新绿原酸、绿原酸、隐绿原酸、芦丁、异槲皮苷、紫云英苷共6个质量标志物的含量分别为0.075~1.463 mg·g^(-1)、2.511~11.940 mg·g^(-1)、0.842~2.921 mg·g^(-1)、0.214~2.546 mg·g^-1)、0.330~2.822 mg·g^(-1)、0.113~0.828 mg·g^(-1)。结论通过多元统计、“成分-靶点-通路”网络和多指标定量预测分析的桑叶质量标志物,为桑叶药材的质量评价体系建立以及药效物质研究奠定基础。Objective To explore potential quality markers(Q-Marker)of mulberry leaves based on“component-target-pathway”network,and determined the contents of Q-Marker.Methods The fingerprints of fifteen batches of mulberry leaves were established by HPLC.The common peaks were identified.The similarity evaluation was conducted.Then,the Q-Marker of mulberry leaves were identified by the multivariate statistical analysis methods and the network pharmacology.Meanwhile,The contents of related components were determined by HPLC.Results The nine common peaks were confirmed by fingerprints of fifteen batches of mulberry leaves.And six chromatographic peaks were identified by reference substances.The similarities were ranged from 0.908 to 0.999.The 15 batches of materials were grouped into two categories.The biomarker was screened by taking the variable importance in projection(VIP)value>1 as the standard,which were chlorogenic acid,rutin,isoquercitri n,astragaloside,cryptochlorogenic acid,and neochlorogenic acid.Based on network pharmacology,the six components may exert hypoglycemic,lipid-lowering and anti-inflammatory effect through T cell receptor signaling pathway,C-type lectin receptor signaling pathway,MAPK signaling pathway and other signal pathways.So they could be used as potential Q-Marker of mulberry leaves.The contents of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,rutin,isoquercitrin and astragaloside were determined.The contents of above 6 components were 0.075-1.463 mg·g^(-1)、2.511-11.940 mg·g^(-1)、0.842-2.921 mg·g^(-1)、0.214-2.546 mg·g^(-1)、0.330-2.822 mg·g^(-1)、0.113-0.828 mg·g^(-1).Conclusions The Q-marker of mulberry leaves are analyzed and predicted by multivariate statistical analysis and“component-target-pathway”network and multi-indicator quantification,which lays the foundation for the establishment of the quality evaluation system and the study of the medicinal substance.

关 键 词：桑叶 多元统计分析 网络药理学 含量测定 质量标志物 

分 类 号：R917[医药卫生—药物分析学]