中国药物警戒 ›› 2022, Vol. 19 ›› Issue (11): 1196-1201.
DOI: 10.19803/j.1672-8629.20210361

• 基础与临床研究 • 上一篇    下一篇

黄芪甲苷治疗溃疡性结肠炎和肝脏损伤共病的分子机制网络药理学研究

臧凯宏1,2, 刘丽丽1, 吴建军1, 高甜甜1, 秦红岩3,*   

  1. 1甘肃中医药大学药学院,甘肃 兰州730000;
    2甘肃省中药药理与毒理学重点实验室,甘肃 兰州730000;
    3兰州大学第一医院药剂科,甘肃 兰州730000
  • 收稿日期:2021-04-19 发布日期:2022-11-17
  • 通讯作者: *秦红岩,女,主任药师,副教授,结肠炎性肝病药物治疗。E-mail:candyqinhy@163.com
  • 作者简介:臧凯宏,男,博士,副教授,中药药理。
  • 基金资助:
    国家自然科学基金资助项目（81860728,81770657）; 甘肃省自然科学基金资助项目（17JR5RA162）

Molecular mechanism of astragaloside IV in the treatment of ulcerative colitis and liver injury comorbidity based on network pharmacology

ZANG Kaihong1,2, LIU Lili1, WU Jianjun1, GAO Tiantian1, QIN Hongyan3,*   

  1. 1Gansu University of Traditional Chinese Medicine, Lanzhou Gansu 730000, China;
    2Gansu Key Laboratory of Pharmacology and Toxicology of Traditional Chinese Medicine, Lanzhou Gansu 730000, China;
    3Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou Gansu 730000, China
  • Received:2021-04-19 Published:2022-11-17

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摘要： 目的 研究黄芪甲苷治疗溃疡性结肠炎（UC）和肝脏损伤共病的药理作用机制,为黄芪甲苷临床应用提供理论依据。方法 利用PharmMapper和DRAR-CPI数据库分析黄芪甲苷活性作用靶点,利用GeneCards和OMIM数据库检索UC或肝脏损伤疾病靶点。将黄芪甲苷靶点分别与UC和肝脏损伤疾病靶点进行映射;应用Cytoscape软件构建黄芪甲苷治疗UC与肝脏损伤成分-疾病靶点网络,将结果导入STRING数据库构建蛋白-蛋白互作网络,分析黄芪甲苷治疗UC与肝脏损伤共同靶点;利用DAVID数据库进行GO富集分析和KEGG信号通路分析,利用分子对接技术对黄芪甲苷与关键靶点的结合进行验证。结果 共筛选得到黄芪甲苷活性靶点322个,其中抗UC靶点202个,抗肝脏损伤靶点219个,152个靶点为黄芪甲苷抗UC和肝脏损伤的共同作用靶点。KEGG分析结果显示,黄芪甲苷治疗UC和肝脏损伤的共同机制涉及磷脂酰肌醇3激酶-蛋白激酶B（PI3K-AKT）、叉头状转录因子O亚家族蛋白（FoxO）、JAK-STAT、过氧化物酶体激活物增殖受体（PPAR）及丝裂原活化蛋白激酶（MAPK）等信号通路对免疫应答反应、炎症因子表达、细胞增殖分化等过程的调控。结论 黄芪甲苷治疗UC和肝脏损伤共病的作用机制涉及AKT、FoxO、STAT、PPAR及MAPK等信号调节过程,免疫应答反应、炎症因子表达、细胞增殖分化调控等过程在黄芪甲苷治疗UC和肝损伤共病中发挥重要作用。

关键词: 黄芪甲苷, 溃疡性结肠炎, 肝脏损伤, 网络药理学, 作用机制

Abstract: Objective To explore the pharmacological mechanism of Astragaloside IV in the treatment of ulcerative colitis and liver injury so as to provide evidence for clinical use of Astragaloside IV. Methods The action targets of Astragaloside IV for treating ulcerative colitis or liver injury were analyzed by searching PharmMapper and DRAR-CPI databases. GeneCards and OMIM databases were used to search for and screen the targets of ulcerative colitis and liver injury. The targets of Astragaloside IV were mapped to the disease targets of ulcerative colitis and liver injury respectively. STRING database was used to construct a “component-target-disease” network of Astragaloside IV for the treatment of ulcerative colitis and liver injury. The obtained results were further input into STRING database to analyze the protein-protein interactions in order to find the same targets related to ulcerative colitis and liver injury, and the DAVID database was used to conduct GO classification enrichment and KEGG signal pathway enrichment analysis. The key targets Astragaloside IV bounds to were validated using molecular docking techniques. Results A total of 322 targets related to Astragaloside IV were screened, including 202 anti-ulcerative colitis targets and 219 anti-liver injury targets, and 152 targets were involved in treating both ulcerative colitis and liver injury. Results from KEGG analysis showed that the shared mechanisms of Astragaloside IV against both ulcerative colitis and liver injury involved PI3K-Aktsignaling, FoxO signaling, JAK-STAT signaling, PPAR signaling and MAPK signaling pathways, which might have some effect on the processes of immune response, production of inflammatory cytokines, cells proliferation and differentiation. Conclusion The common therapeutic mechanism of Astragaloside IV against ulcerative colitis and liver injury involve PI3K-AKT signaling, FoxO signaling, JAK-STAT signaling, PPAR signaling and MAPK signaling pathways. Immune response, expressions of inflammatory factors, cell proliferation and differentiation regulation play an important role in the treatment of UC and liver injury comorbidity with Astragaloside IV.

Key words: Astragaloside IV, ulcerative colitis, liver injury, network pharmacology, molecular mechanism

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