基于网络药理学、含量测定及活性评价探讨沙棘叶质量标志物及其潜在药用价值  

Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology,content determination,and activity evaluation

作　　者：何倩 杨凯琳[2,3] 吴欣艳 张博 张春红[1] 何春年[2,3] 肖培根[2,3] HE Qian;YANG Kai-lin;WU Xin-yan;ZHANG Bo;ZHANG Chun-hong;HE Chun-nian;XIAO Pei-gen(Baotou Medical College,Baotou 014060,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China;Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,Ministry of Education,Beijing 100193,China;Institute for Interdisciplinary Information Sciences,Tsinghua University,Beijing 100193,China)

机构地区：[1]包头医学院,内蒙古包头014060 [2]中国医学科学院北京协和医学院药用植物研究所,北京100193 [3]教育部中草药物质基础与资源利用重点实验室,北京100193 [4]清华大学北京中医药交叉研究所,北京100193

出　　处：《中国中药杂志》2023年第20期5487-5497,共11页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2021YFE0190100);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-D-202005);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-071)。

摘　　要：药食两用植物沙棘Hippophae rhamnoides的叶,已被批准为普通食品原料,同时还具有传统药用记载和广泛的药理活性,显示出较好的药用价值潜力,但其潜在的药效物质和作用机制尚不清楚。同时,由于沙棘叶来源广泛,品质变异大,没有相应的质量评价标准。该研究采用网络药理学和分子对接技术预测沙棘叶的活性成分、核心靶点、关键通路及其潜在治疗疾病,同时结合UPLC-DAD含量测定、化学指纹图谱分析,遴选出沙棘叶潜在的质量标志物(Q-marker),并利用酶活性抑制方法进行初步验证。结果表明,沙棘叶对多种消化道疾病、代谢类疾病、肿瘤和自身免疫性疾病等均具有潜在干预作用,与传统应用和现代药理学活性研究结果相符,作用核心靶点包含PTPN11、AKT1、PIK3R1、ESR1、SRC等;关键信号通路主要涉及PI3K-AKT、MAPK、HIF-1等。沙棘叶发挥药效活性与其含有丰富且结构多样的黄酮类和鞣质类成分密切相关,其中槲皮苷、水仙苷和鞣花酸可作为沙棘叶的质量标志物。该研究为沙棘叶的质量控制和后续药用价值的深入开发利用提供参考。The leaves of sea buckthorn(Hippophae rhamnoides),considered as common food raw materials,have records of medicinal use and diverse pharmacological activities,showing a potential medicinal value.However,the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear.In addition,due to the extensive source and large variety variations,the quality evaluation criteria of sea buckthorn leaves remain to be developed.To solve the problems,this study predicted the main active components,core targets,key pathways,and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking.Furthermore,ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint,on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method.The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases,metabolic diseases,tumors,and autoimmune diseases,which were consistent with the ancient records and the results of modern pharmacological studies.The core targets of sea buckthorn leaves included PTPN11,AKT1,PIK3R1,ESR1,and SRC,which were mainly involved in the PI3K-AKT,MAPK,and HIF-1 signaling pathways.In conclusion,the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins,among which quercitrin,narcissoside,and ellagic acid can be used as the quality markers of sea buckthorn leaves.The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

关 键 词：沙棘叶 质量标志物 网络药理学 指纹图谱 

分 类 号：R284.1[医药卫生—中药学] R285[医药卫生—中医学]