基于指纹图谱-网络药理学-多指标定量分析预测树参中的差异活性成分  

Research on quality marker of Dendropanax dentiger for treatment of rheumatoid arthritis based on fingerprint-network pharmacology-multi-index quantification

作　　者：范欣荣 张乐怡 罗莎 袁宙新 李帆 薛畅 王慧玉 姜程曦 FAN Xinrong;ZHANG Leyi;LUO Sha;YUAN Zhouxin;LI Fan;XUE Chang;WANG Huiyu;JIANG Chengxi(Department of Pharmacy,Lishui Hospital of Traditional Chinese Medicine Affiliated Hospital of Zhejiang Chinese Medical University,Lishui 323000,China;School of Pharmacy,Wenzhou Medical University,Wenzhou 325035,China;School of Health Sciences,Chongqing Vocational Institute of Engineering,Chongqing 400000,China;Zhejiang Jolly Pharmaceutical Co.,Ltd.,Huzhou 313000,China)

机构地区：[1]浙江中医药大学附属丽水中医院药剂科,浙江丽水323000 [2]温州医科大学药学院,浙江温州325035 [3]重庆理工职业学院卫生健康学院,重庆400000 [4]浙江佐力药业股份有限公司,浙江湖州313000

出　　处：《中草药》2025年第6期2122-2134,共13页Chinese Traditional and Herbal Drugs

基　　金：丽水市自筹类公益性技术应用研究项目(2022SJZC037);浙江省中医药管理局共建科技计划项目(GZY-ZJ-KJ-23098);浙江省中医药科技计划项目(2024ZR205);灵泽片主成分温莪术药材质量提升及其真实世界临床研究(KJHX2206)。

摘　　要：目的基于指纹图谱和网络药理学方法,分析预测树参Dendropanax dentiger的差异活性成分,并建立其定量分析方法,为树参的质量控制提供参考。方法采用HPLC法建立树参的指纹图谱并结合化学计量学筛选不同产地树参的主要差异成分。通过网络药理学方法,确定树参特征成分治疗类风湿关节炎(rheumatoid arthritis,RA)的核心靶点和关键通路,绘制“成分-核心靶点-通路”网络图,以预测树参抗RA的差异活性成分。以28批树参药材为研究对象,对其差异活性成分进行含量测定,确定出树参的差异活性成分。结果建立了28批树参药材的指纹图谱,标定了13个共有峰,并指认出5个共有峰,分别为原儿茶酸、紫丁香苷、绿原酸、异绿原酸A、异绿原酸C。通过化学计量学分析,初步筛选出紫丁香苷、绿原酸、异绿原酸A和异绿原酸C为主要差异性成分。网络药理学分析显示,紫丁香苷、绿原酸、异绿原酸A、异绿原酸C可能通过前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)、半胱天冬酶-3(Caspase-3,CASP3)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP2)、基质金属蛋白酶-3(matrix metalloproteinase-3,MMP3)、E-选择素(E-selectin,SELE)、P-选择素(P-selectin,SELP)、前列腺素内过氧化物合酶1(prostaglandin-endoperoxide synthase 1,PTGS1)8个核心靶点,影响脂质与动脉粥样硬化、肾素-血管紧张素系统、白细胞介素-17(interleukin-17,IL-17)和肿瘤坏死因子(tumor necrosis factor,TNF)等信号通路,从而发挥治疗RA的作用。最终确定紫丁香苷、绿原酸、异绿原酸A、异绿原酸C可作为树参治疗RA的差异活性成分。结论建立的质量评价方法准确可靠,结合网络药理学筛选出的差异活性成分可为树参质量控制提供依据,并为其治疗RA的作用机制提供参考。Objective To analyze and predict the differential active components of Dendropanax dentiger using fingerprint and network pharmacology methods,establish quantitative analysis methods,and provide a reference for the quality control of D.dentiger.Methods High-performance liquid chromatography(HPLC)was used to establish the fingerprint of D.dentiger,and chemometric analysis was employed to screen the main differential components from different origins.Furthermore,network pharmacology was applied to identify the core targets and key pathways of the characteristic components of D.dentiger in the treatment of rheumatoid arthritis(RA).A“component-core target-pathway”network was constructed to predict the differential active components of D.dentiger for anti-RA effects.The content of the differential active components was determined in 28 batches of D.dentiger samples,and the final differential active components were identified.Results The HPLC fingerprint of 28 batches of D.dentiger samples was established,with 13 common peaks identified,including 5 peaks assigned as protocatechuic acid,syringin,chlorogenic acid,isochlorogenic acid A,and isochlorogenic acid C.Chemometric analysis preliminarily identified syringin,chlorogenic acid,isochlorogenic acid A,and isochlorogenic acid C as the main differential components.Network pharmacology analysis revealed that syringin,chlorogenic acid,isochlorogenic acid A,and isochlorogenic acid C might exert therapeutic effects on RA through 8 core targets,including prostaglandin-endoperoxide synthase 2(PTGS2),caspase 3(CASP3),epidermal growth factor receptor(EGFR),matrix metalloproteinase-2(MMP2),matrix metalloproteinase-3(MMP3),E-selectin(SELE),P-selectin(SELP),and prostaglandinendoperoxide synthase 1(PTGS1),influencing signaling pathways such as lipid and atherosclerosis,renin-angiotensin system,interleukin-17(IL-17),and tumor necrosis factor(TNF).Finally,syringin,chlorogenic acid,isochlorogenic acid A,and isochlorogenic acid C were determined as the differential active components

关 键 词：树参 差异活性成分 质量标志物 指纹图谱 网络药理学 多成分定量 原儿茶酸 紫丁香苷 绿原酸 异绿原酸A 异绿原酸C 

分 类 号：R286.2[医药卫生—中药学]