基于网络药理学探讨熟地黄治疗溃疡性结肠炎的作用机制

Discussion on the Mechanism of Action of Radix Rehmanniae Praeparata in Treating Ulcerative Colitis Using Network Pharmacology

摘要: 目的：利用网络药理学研究策略，结合中药对机体代谢的调控作用，探讨熟地黄防治溃疡性结肠炎的直接作用及间接调控机制。方法：通过网络数据库，筛选得到熟地黄中活性成分可直接作用的病理靶点，构建“活性成分–蛋白靶点–病理机制”直接交互网络；同时，从中药影响内源性物质代谢的角度，筛选出熟地黄参与代谢调控的通路及相关代谢酶。利用分子对接模拟实验，验证所筛选关键靶蛋白与熟地黄中有效成分的结合活性。结果：从数据库中共筛选得到熟地黄中20个潜在活性成分和25个核心靶点，主要涉及细胞表面离子通道等信号通路；分子对接及代谢通路富集分析显示，所筛选关键靶蛋白与熟地黄中有效成分具有良好的结合活性，熟地黄对脂质代谢具有调控作用，亦可作为防治溃疡性结肠炎的间接调控机制。结论：熟地黄防治溃疡性结肠炎有多成分、多靶点、多效性的作用特点，并可能通过调控机体代谢进而发挥防治功效。本研究为后续道地药材资源的开发、熟地黄防治溃疡性结肠炎的药效物质基础及作用机制研究提供了理论支撑。

Abstract: Objective: To explore the direct and indirect mechanisms of Radix Rehmanniae Praeparata (RRP) in preventing and treating ulcerative colitis by using the research strategy of network pharmacology, and by combining with the metabolic regulation of traditional Chinese medicines. Methods: Through the network database, we screened the pathological targets of the active ingredients in RRP, and constructed a direct interaction network of “active ingredient-protein target-pathological mechanism”. Meanwhile, we analyzed its metabolic regulation by evaluating the effects on endogenous substance metabolism. Additionally, endogenous substances and related metabolic enzymes involved in its regulatory effects were screened. The molecular docking simulation experiment was used to verify the binding activities of the screened target proteins with the active ingredients. Results: A total of 20 potential active ingredients and 25 core targets were identified from the database, which were mainly involved in cell surface ion channels and other signaling pathways; the molecular docking results and metabolic pathway enrichment analyses showed that the screened key target proteins had good binding activities with the active ingredients in RRP, and RRP had a regulatory effect on lipid metabolism. It can also be used as an indirect regulatory mechanism to prevent ulcerative colitis. Conclusion: The prevention and treatment of ulcerative colitis by RRP is characterized by multi-components, multi-targets, wide range of efficacy outputs, and it may exert preventive and curative effects through the modulation of organismal metabolism. The present study provides theoretical support for the development of local medicinal resources and the study of the pharmacological basis and mechanism of action of RRP in the prevention and treatment of ulcerative colitis.