基于网络药理学及分子对接探究咖啡酰奎宁酸抗氧化应激作用机制

Probing the Mechanism of Anti-oxidative Stress Action of Caffeoylquinic Acid Based on Network Pharmacology and Molecular Docking

摘要

本文研究目的为使用网络药理学及分子对接技术分析咖啡酰奎宁酸类化合物（CQAs）抗氧化应激作用的相关机制。首先通过数据库获得咖啡酰奎宁酸类化合物作用靶点及氧化应激相关作用靶点，构建“咖啡酰奎宁酸-靶点”网络并进行化合物与靶点关系分析，将所得靶点进行基因本体论分析（GO）及京都基因与基因组百科全书（KEGG）通路分析，并将得到的关键靶点与咖啡酰奎宁酸类化合物进行分子对接验证。网络药理学结果表明咖啡酰奎宁酸类化合物发挥抗氧化应激作用涉及包括MMP9、MMP2、APP、REN、MMP1等潜在关键靶点蛋白67个，靶点间相互作用关系共194条，涉及膀胱癌、泛素-蛋白酶体通路、糖尿病并发症中的AGE-RAGE信号通路等40条相关通路。分子对接证明了咖啡酰奎宁酸类化合物可以与氧化应激作用的关键靶点以氢键等相互作用结合，发挥其抗氧化应激活性。本研究预测了咖啡酰奎宁酸类化合物发挥抗氧化应激作用的多个靶点和多条通路，并通过分子对接进行了初步验证，为咖啡酰奎宁酸类化合物抗氧化应激机制的研究和生物利用率的提高提供一定的理论依据。

Abstract

This study aims to analyze the mechanism of the antioxidative-stress effects of caffeoylquinic acid analogs through network pharmacology and molecular docking techniques. First, the targets of caffeoylquinic acid compounds and oxidative stress-related targets are retrieved from databases, and a "caffeoylquinic acid-target" network is constructed to analyze the relationship between compounds and targets. The obtained targets are then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The identified key targets are further validated through molecular docking with caffeoylquinic acid compounds. Network pharmacology results show that 67 potential key target proteins, including MMP9, MMP2, APP, REN, and MMP1, are involved in the antioxidative-stress effects of caffeoylquinic acid compounds. These targets exhibit 194 inter-target interactions and are associated with 40 related pathways, such as bladder cancer, the ubiquitin-proteasome pathway, and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking demonstrates that caffeoylquinic acid analogs bind to key oxidative stress-related targets through interactions such as hydrogen bonding, thereby exerting antioxidative-stress activity. This study predicts multiple targets and pathways through which caffeoylquinic acid analogs exert antioxidative-stress effects and provides preliminary validation through molecular docking. It offers a theoretical basis for further research on the antioxidative-stress mechanism and bioavailability of caffeoylquinic acid analogs.

关键词

网络药理学 / 咖啡酰奎宁酸类化合物 / 氧化应激 / 作用机制 / 分子对接

Key words

Network pharmacology / caffeoylquinic acid analogs / oxidative stress / mechanism of action / molecular docking

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基金资助

山东省重点研发计划(2024TZXD007)

山东省科技型中小企业创新能力提升工程(2024TSGC0483)