天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (1): 137-154.doi: 10.16333/j.1001-6880.2024.1.016

• 数据研究 • 上一篇    下一篇

基于数据挖掘、网络药理学及实验验证探讨中药治疗变应性鼻炎的用药规律及相关药理分析

王笑雨1,王   召1,曹利华1,贺红娟1,王真真1,李秀敏2,苗明三1*   

  1. 1河南中医药大学中医药科学院,郑州 450046;2纽约医学院 微生物和免疫学科,纽约 10595
  • 出版日期:2024-01-23 发布日期:2024-01-23
  • 基金资助:
    河南省重大公益专项(201300310100);河南省药品监督管理局科技计划(2020DB050-55);河南省博士后科研项目(202103093);河南省高等学校重点科研项目(23A360016)

Medication rule analysis and pharmacological analysis of traditional Chinese medicine treating allergic rhinitis based on data mining,network pharmacology and experimental validation

WANG Xiao-yu1,WANG Zhao1,CAO Li-hua1,HE Hong-juan1,WANG Zhen-zhen1,LI Xiu-min2,MIAO Ming-san1*   

  1. 1 Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,China;2Microbiology and Immunology,New York Medical College,New York 10595,USA
  • Online:2024-01-23 Published:2024-01-23

摘要:

基于中国知网、万方、维普数据库,以“中药+变应性鼻炎”“中药+过敏性鼻炎”“中药+鼻鼽”为主题,选取2000年1月至2022年2月公开发表的期刊文献,按照纳入与排除标准筛选临床治疗AR的中药方剂,统计高频药物的用药频次、剂量、药味、药性、归经、功效等,并进行关联规则和系统聚类分析,共筛选符合标准的中药方剂有252首,共223味中药,其中用药频次 ≥ 30的高频中药有21种,以解表药和补虚药为主,药性以辛温为主,关联规则挖出21对频次 ≥ 64的药物组合,其中黄芪-辛夷药对出现频次最高。利用网络药理学对黄芪-辛夷药对的活性成分、靶点蛋白和通路等进行分析,结果显示黄芪-辛夷药对共有48个有效成分,对应的潜在靶点共306个,包括PTGS2、HSP90、CALM1、NOS2、CHRM1等;GO富集和KEGG通路分析显示核心靶点参与对外源性刺激的反应、氧化还原酶活性等多项进程,并通过神经活性配体-受体相互作用通路、钙离子信号通道等通路作用于AR,分子对接结果显示黄芪-辛夷可能通过细辛素、芒柄花素、山柰酚、槲皮素作用于PTGS2、CHRM1、CYP1B1等靶点发挥治疗AR的作用。基于上述结论进行体内实验验证,结果证实黄芪-辛夷药对能够有效降低AR小鼠血清、肺泡灌洗液以及鼻腔灌洗液中组胺、总IgE、RW特异性IgE、TNF-α和IL-6等炎性因子的水平,升高抗炎因子IL-10的水平,抑制炎症反应的发展,显著改善AR小鼠挠鼻和喷嚏症状,并降低肺组织中PTGS2、HSP90、NOS2蛋白的表达水平。因此,本研究表明黄芪-辛夷药对可能是通过抑制HSP90/PTGS2/NOS2通路进而抑制炎症反应、缓解AR小鼠的症状从而发挥治疗AR的作用。

关键词: 变应性鼻炎, 用药规律, 关联规则, 网络药理学, 分子对接, 体内实验验证

Abstract:

The full-text search was conducted with “traditional Chinese medicine (TCM)+allergic rhinitis” theme in CNKI, Wanfang and VIP database.The literature published from January 2000 to February 2022 were selected,and clinical TCM prescriptions for AR were collected under “inclusion and exclusion” criteria.The statistics processing of drug frequency,dosage,flavor,property, channel tropism,efficacy and association rule analysis were carried out.A total of 252 TCM prescriptions were obtained, including 223 different Chinese medicines.And there were 21 Chinese medicines used in the treatment of AR with high frequency ≥ 30,mainly with exterior-releasing and supplementing efficacies.Warm and pungent were main flavors among high-frequency TCM.In association rule analysis,21 combinations of TCM with high frequency ≥ 64 were found out;among them,Huangqi-Xinyi drug pair was utilized in the highest frequency.The network pharmacological analysis indicated that Huangqi-Xinyi has 48 active compounds and 306 corresponding protein targets,including PTGS2,HSP90,CALM1,NOS2,and CHRM1.Go and KEGG analysis revealed that core targets predominantly effected on AR by responsing to xenobiotic stimulus,oxidoreductase activity,neuroactive ligand-receptor interaction and calcium signaling pathway.Molecular docking results showed that Huangqi-Xinyi drug pair probably treated AR by acting on PTGS2,CHRM1,CYP1B1 targets through asarinin,formononetin,kaempferol and quercetin.In vivo experiment showed that Huangqi-Xinyi drug pair effectively decreased the level of histamine,total IgE,RW-specific IgE,TNF-α and IL-6 in serum,nasal lavage fluid and bronchoalveolar lavage fluid of AR mice,and increased the level of anti-inflammatory factor IL-10 in above-mentioned serum and fluids.Also,Huangqi-Xinyi drug pair significantly decreased rubbing and sneezing times of AR mice and inhibited the protein expression of PTGS2,HSP90 and NOS2.Thus,this study clarified that Huangqi-Xinyi drug pair had a therapeutic effect on AR by inhibiting HSP90/PTGS2/NOS2 pathway,thereby inhibited inflammation and relieved rubbing and sneezing symptoms of AR mice.

Key words: allergic rhinitis, medication rule, association rule, network pharmacology, molecular docking, in vivo experiment

中图分类号:  R285