天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (4): 662-676.doi: 10.16333/j.1001-6880.2023.4.014

• 数据研究 • 上一篇    下一篇

基于网络药理学的七首复方治疗溃疡性结肠炎的作用机制研究

黄   友1,李   莎1,吴秋红1,朱   芮1,林   夏1,杨莎莎1,傅超美1*,张   臻1,2*   

  1. 1成都中医药大学药学院 西南特色中药资源国家重点实验室,成都 611137;2四川新绿色药业科技发展有限公司 国家中医药管理局“中药配方颗粒质量与疗效评价重点研究室”,彭州 611930
  • 出版日期:2023-04-24 发布日期:2023-04-24
  • 基金资助:
    国家自然科学基金青年基金(81803742);四川省科技厅四川省科技计划(2021YJ0251);四川省中医药管理局中医药科研专项(2021MS109);成都中医药大学杏林学者青年学者专项(QNXZ2019031)

Study on the mechanism of seven classic prescriptions for treating ulcerative colitis based on network pharmacology

HUANG You1,LI Sha1,WU Qiu-hong1,ZHU Rui1,LIN Xia1,YANG Sha-sha1,FU Chao-mei1 *,ZHANG Zhen1,2 *   

  1. 1State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;2Key Laboratory of Quality Control and Efficacy Evaluation of Traditional Chinese Medicine Formula Granules,Sichuan New Green Medicine Science and Technology Development Co.,Ltd.,Pengzhou 611930,China
  • Online:2023-04-24 Published:2023-04-24

摘要: 利用网络药理学和生物信息学技术分析《溃疡性结肠炎中医诊疗专家共识意见》(2017)七首中医经典复方治疗溃疡性结肠炎(ulcerative colitis,UC)的作用机制,以筛选治疗UC的潜在共有的重要成分、靶点及通路,同时分析每首复方独有的重要成分、靶点及通路,并对重要证型脾肾阳虚型UC的重要靶点进行实验验证。通过网络药理学方法,筛选出7首中医经典复方的4个共有重要成分、42个共有重要靶点、30个独有重要成分、14个独有重要靶点;KEGG通路分析显示,共有重要靶点主要涉及炎症与疾病相关通路;每首复方独有通路主要涉及HIF-1、T细胞受体等炎症相关通路以及阿尔茨海默病等疾病相关通路;采用AutoDock vina 对重要成分和重要靶点进行分子对接验证;采用“饮食失节+劳倦过度+番泻叶灌胃+葡聚糖硫酸钠”建立病证结合的大鼠脾肾阳虚型UC模型,灌胃给予附子理中丸混悬液(1.2 g/kg)21 d后,采用ELISA验证其重要靶点。结果表明,附子理中丸能显著降低脾肾阳虚型UC模型大鼠血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平(P<0.001)。本研究初步提示了七首经典复方治疗UC的潜在共性作用机制为消除炎症、调节免疫、调节细胞凋亡及抗癌等作用;附子理中丸可以调控TNF、IL-6等重要靶点,发挥治疗脾肾阳虚型UC的作用,其机制可能与调控T细胞受体等炎症通路相关;β-谷甾醇、豆甾醇、白桦脂酸、山柰酚等参与不同UC中医证型的治疗,为治疗不同UC中医证型的潜在药物发现及临床精准治疗提供参考,也为UC辨证分型的潜在特异性评价指标提供新思路。

关键词: 共有靶点, 共有成分, 附子理中丸, 炎性细胞因子, 特异性评价指标

Abstract:

Network pharmacology and bioinformatics techniques were used to analyze the mechanisms of seven classic prescriptions of traditional Chinese medicine (TCM) syndrome types from The Expert Consensus on Traditional Chinese Medicine Diagnosis and Treatment of Ulcerative Colitis (2017) for treating ulcerative colitis (UC) to screen common and special important components,targets,and pathways in UC treatment.The important targets of UC with spleen and kidney Yang deficiency (SKYD-UC) were verified experimentally.Four common important components,42 common important targets,30 special important components,and 14 special important targets were screened from seven classic prescriptions for treating UC by network pharmacology.According to KEGG pathway analysis,common important targets mainly involved inflammation and disease-related pathways.The special pathways mainly involved disease-related pathways (such as Alzheimer′s disease) and inflammatory-related pathways (such as HIF-1 and T cell receptors).AutoDock Vina was employed for the molecular docking verification of important components and targets.Animal models of SKYD-UC were established by "diet deficiency + excess fatigue + senna leaf gavage + dextran sulfate sodium".Fuzi-Lizhong pill suspension (1.2 g/kg) was given for 21 days,and ELISA was carried out to verify the important targets.In animal experiments,compared with the SKYD-UC group,the Fuzi-Lizhong pill group can effectively reduce tumor necrosis factor-α (TNF-α),and interleukin-6 (IL-6) levels in the SKYD-UC rats (P<0.001).The common mechanism of the seven classic prescriptions for treating UC may be regulating immunity,eliminating inflammation,regulating apoptosis,anti-cancer,etc.Fuzi-Lizhong pill can regulate important targets such as TNF-α and IL-6 and participates in the treatment of SKYD-UC rats,where the mechanism may be related to the regulation of T cell receptors and other pathways.At the same time,β-sitosterol,stigmasterol,betulinic acid,kaempferol,and other important components may be involved in treating different TCM syndromes of UC.This provides a reference for the potential drug discovery and clinical precision treatment of UC with different TCM syndromes as well as for the potential specific evaluation index of UC syndrome differentiation.

Key words: common important targets, common important components, Fuzi-Lizhong pill, inflammatory cytokines, specific evaluation indexes

中图分类号:  R285