指纹图谱结合网络药理学及实验验证的黄连膏治疗特应性皮炎质量标志物(Q-marker)预测  

Prediction of quality markers(Q-marker)based on fingerprinting combined with network pharmacology and experimental validation of Huanglian ointment for atopic dermatitis

作　　者：林洁 李维[2] 曾山 黎霖 任建华 李丹阳 刘瑛[2] 邹亮[6] LIN Jie;LI Wei;ZENG Shan;LLin;REN Jian-hua;LI Dan-yang;LIU Ying;ZOU Liang(Department of Traditional Chinese,Affiliated Hospital ofChengdu University,Chengdu 610081,Sichuan;School of Preclinical Medicine,ChengduUniversity,Chengdu 610106,Sichuan;Drug Inspection and Research Institute of Chengdu,Chengdu 610041,Sichuan;Si Chuang Hou Sheng Tian Zuo Pharmaceutical Co.,Ltd.,Chengdu 611130,Sichuan;School of Clinical MedicineFood and Bioengineering,Chengdu University,Chengdu 610106,Sichuan;School of Food and Bioengineering,Chengdu University,Chengdu 610106,Sichuan)

机构地区：[1]成都大学附属医院中药剂科,四川成都610081 [2]成都大学基础医学院,四川成都610106 [3]成都市药品检验研究院,四川成都610041 [4]四川厚生天佐药业有限公司,四川成都611130 [5]成都大学临床医学院,四川成都610106 [6]成都大学食品与生物工程学院,四川成都610106

出　　处：《中药与临床》2023年第6期55-64,共10页Pharmacy and Clinics of Chinese Materia Medica

基　　金：四川省科技计划重点研发项目(2020YFN0152);成都市科技创新平台项目(2022-YF04-00126-JH);成都市卫生和计划生育委员会临床药学重点学科。

摘　　要：目的:建立黄连膏的指纹图谱,结合网络药理学和实验验证分析其治疗特应性皮炎(Atopic dermatitis,AD)的机制,预测其潜在的质量标志物(Q-Marker),为其质量控制和临床应用提供依据。方法:建立黄连膏的HPLC指纹图谱,对共有峰进行指认和归属,应用网络药理学筛选和分析黄连膏相关成分的作用靶点和通路,预测其抗AD潜在的Q-Marker;建立1-氯-2,4-二硝基苯(DNCB)诱导的AD小鼠模型,对预测结果进行验证。结果:指纹图谱共标定23个共有峰,并指认出5个色谱峰;将5个成分经网络药理学分析,筛选出EGFR、IL-10、PTGS2、VCAM1、STAT3、ICAM1等作用靶点,癌症的途径、脂质与动脉粥样硬化、TNF信号通路、细胞凋亡等关键信号通路,以“Q-Marker五原则”为核心,结合指纹图谱及网络药理学分析结果,初步预测小檗碱、姜黄素、藁本内酯、芝麻素、芝麻酚为黄连膏潜在的Q-Marker。动物实验验证,黄连膏能有效改善AD模型小鼠皮损(p<0.001),减少抓挠次数(p<0.001),降低血清炎症因子IL-6,IFN-γ,TNF-α水平(p<0.001),减轻皮肤角化过度和表皮及真皮的增厚,减少肥大细胞数量。结论:本研究建立的HPLC指纹图谱方法稳定可行,结合网络药理学及实验验证发现黄连膏中5个成分与其抗皮炎功效密切相关,为黄连膏的质量控制提供参考,同时也为黄连膏药效关联物质基础的研究及作用机制的探索奠定基础。Objective:This study established the fingerprint of Huanglian ointment.Through network pharmacology and experimental verification,The mechanism of Huanglian ointment treating atopic dermatitis(AD)was analyzed,and its potential quality marker(Q-marker)was predicted,which provided basis for its quality control and clinical application.Method:A method for HPLC fingerprint Huanglian ointment was developed which was applied to identify and assign the common peaks.Then network pharmacology methods was used to screen and analyze the action targets and pathways of related components of Huanglian ointment,and predicted the potential Q-marker of Huanglian ointment in anti-AD effect.Finally the mice model of AD induced by 1-chloro-2,4-dinitrobenzene(DNCB)was established to verify the prediction results.Result:The results showed that a total of 23 common peaks were calibrated in the ffngerprint,and 5 chromatographic peaks were identiffed.The ffve components were analyzed by network pharmacology,and the action targets of EGFR,IL-10,PTGS2,VCAM1,STAT3,ICAM1,cancer pathway,lipid and atherosclerosis,-TNF signaling pathway,apoptosis and other key signaling pathways were screened.Taking the"five principles of Q-marker"as the core,combined with the results of ffngerprint and network pharmacology analysis,it was preliminarily predicted that berberine,curcumin,ligustilide,sesamin and sesamol were the potential Q-markers of Huanglian ointment.Animal validation experiments showed that compared with the model group,Huanglian ointment can effectively improve the skin lesions of AD model mice(p<0.001),reduce the number of scratches(p<0.001),and reduce the serum inflammatory factors IL-6 and IFN-γ,TNF-α level(p<0.001),reduce skin hyperkeratosis and thickening of epidermis and dermis,and reduce the number of mast cells.Conclusion:The established HPLC ffngerprint method in our study is stable and feasible.Combined with network pharmacology and experimental veriffcation,it is found that the ffve components in Huanglian ointment are closely r

关 键 词：黄连膏 指纹图谱 特应性皮炎 网络药理学 经典名方 小檗碱 

分 类 号：R285.5[医药卫生—中药学]