基于数据挖掘与实验验证的抗湿疹中药筛选及活性研究  

Study on screening of traditional Chinese medicine with anti-eczema effect and their activity based on data mining and experimental verification

作　　者：张丹丹[1] 黄玉荣 范佳琪 孔祥鹏 ZHANG Dandan;HUANG Yurong;FAN Jiaqi;KONG Xiangpeng(Department of Pharmacy,Tianjin Hospital,Tianjin 300211,China;College of Traditional Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]天津市天津医院药学部,天津300211 [2]山西中医药大学中药与食品工程学院,山西晋中030619

出　　处：《中草药》2024年第10期3404-3419,共16页Chinese Traditional and Herbal Drugs

基　　金：山西省卫生健康委科研课题(2023096);山西省1331工程(技术)研究中心开放课题(2023-NPT-04);山西中医药大学科技创新培育计划太行本草专项“基础和应用研究专题”(2022PY-TH-10)。

摘　　要：目的通过数据挖掘与实验相结合,筛选抗湿疹中药并评价其活性。方法收集具有抗湿疹活性的中药方剂,筛选后录入Excel软件建立数据库,运用中医传承计算平台V3.0对其高频药物、复方配伍进行关联规则分析,挖掘核心药物及其组合,并对核心药物组合及单味药的抑菌作用进行测定。将40只昆明种小鼠随机分为空白组、模型组、基质组、阳性药组及核心药物组合凝胶组,并采用2,4-二硝基氯苯建立小鼠湿疹模型,验证核心药物组合的抗湿疹药效。应用超高效液相色谱-串联质谱代谢组学技术检测核心药物组合治疗湿疹小鼠前后血清中内源性代谢物,并采用主成分分析及正交偏最小二乘法判别分析等多元统计分析,结合人类代谢数据库(HMDB)等数据库和相关文献指认、鉴定差异代谢物,通过MetaboAnalyst平台富集相关代谢通路。结果筛选得到255首符合标准的抗湿疹中药方剂,包含中药347味,使用频次由高到低分别是黄柏、苦参、蛇床子、白鲜皮、枯矾等清热解毒、清热燥湿中药。通过用药模式分析,并结合《已使用化妆品原料目录(2021年版)》,得到“苦参-蛇床子”核心药物组合。抑菌实验结果表明,苦参抑菌活性优于蛇床子,而二者组合物的抗菌活性有所提高。皮肤形态学观察显示,苦参-蛇床子凝胶组能明显减轻皮损的严重程度,减少皮肤组织炎性细胞的浸润情况。从血清中筛选出与核心药物组合治疗湿疹相关的12种内源性差异代谢物,主要涉及甘油磷脂代谢、谷胱甘肽代谢、甘油酯代谢等代谢通路。结论基于数据挖掘方法从抗湿疹中医方剂中筛选得到14味核心药物,在此基础上进一步结合《已使用化妆品原料目录(2021年版)》确定的苦参-蛇床子组合物呈现较好的抗菌和抗湿疹活性,其抗湿疹药效与调节甘油磷脂代谢、谷胱甘肽代谢、甘油酯代谢等有关,这为其进一步�Objective To screen the traditional Chinese medicine(TCM)with anti-eczema and evaluate activity based on the combination of data mining and experiment.Methods The TCM prescriptions with anti-eczema activity were collected,screened and entered into Excel software to establish the database.The association rules of their high-frequency drugs and compound compatibility were analyzed by using the traditional Chinese Medicine Inheritance and calculation platform V3.0,and the core drugs and their combinations were mined.Moreover,the bacteriostasis of the core drug combinations and single drugs were determined.A total of 40 male Kunming mice were randomly divided into blank group,model group,matrix group,positive group and core drugs combinaton gel groups.The anti-eczema effect of core drugs combination was further verified by eczema model induced by 2,4-dinitrochlorobenzene(DNCB).The endogenous metabolites in serum of eczema mice were detected by ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC-MS)metabolomics.The multivariate statistical analysis was performed to analyze the different metabolites by principal component analysis(PCA)and orthogonal partial least square discriminant analysis(OPLS-DA).Combined with Human Metabolic Database(HMDB)and related literature,these metabolites were identified,and the relevant metabolic pathways were enriched through the MetaboAnalyst platform.Results A total of 255 TCM prescriptions with anti-eczema activity that meet the standard were screened,including 347 traditional Chinese medicines.The frequency of use from high to low was Huangbo(Phellodendri Chinensis Cortex),Kushen(Sophorae Flavescentis Radix,SFR),Shechuangzi(Cnidii Fructus,CF),Baixianpi(Dictamni Cortex),Kufan(Calcined Alumen),and et al.Most of them have the properties of clearing heat and removing toxin,clearing heat and drying dampness.The core drug combination of SFR-CF was obtained by drug association rule analysis and Catalog of Used Cosmetics Raw Materials(2021 edition).The anti-bacterial t

关 键 词：中药 数据挖掘 苦参 蛇床子 抗菌 抗湿疹 代谢组学 苦参-蛇床子 甘油磷脂代谢 谷胱甘肽代谢 甘油酯代谢 

分 类 号：R285[医药卫生—中药学]