基于药效学和网络药理学探讨乌梅丸治疗溃疡性结肠炎方剂精简的可行性

Feasibility of Simplification of Wumei Pill in The Treatment of Ulcerative Colitis Based on Pharmacodynamics and Network Pharmacology

目的:通过评价乌梅丸全方和精简方的药效和网络药理机制,探讨乌梅丸精简方是否可以代替全方治疗溃疡性结肠炎(ulcerative colitis,UC)。方法:以2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzenesulfonic acid,TNBS)诱导的UC大鼠为模型,通过结肠损伤情况、白细胞介素(interleukin,IL)-1β和环氧化酶(cyclooxygenase,COX)-2水平观察乌梅丸全方和精简方对UC大鼠的治疗效果;使用数据库检索乌梅丸全方和精简方的有效成分及其靶点和UC的靶点,取交集后绘制药物-成分-靶点-疾病网络图,构建乌梅丸全方和精简方作用于UC的蛋白互作网络并进行通路分析,分子对接验证乌梅丸全方和精简方的核心成分和核心靶点的结合能力。结果:药效学结果显示与正常组大鼠比较,模型组大鼠的结肠质量长度比升高,结肠组织中IL-1β和COX-2水平较高,差异有统计学意义(P<0.01);乌梅丸全方组、精简方组和阳性药组大鼠的结肠质量长度比下降,IL-1β和COX-2水平降低,差异有统计学意义(P<0.05);药理学结果显示乌梅丸全方和精简方分别有111和99个靶点作用于UC,拓扑分析和通路分析发现乌梅丸全方和精简方作用于UC的核心靶点和核心通路基本类似,分子对接结果显示槲皮素、山奈酚和黄连碱等成分与核心靶点的结合能力较强。结论:药效学和网络药理学结果表明,乌梅丸精简后治疗UC具有可行性。

Objective:To discuss whether Wumei Pills'simplified prescription could replace the full prescriptions in the treatment of ulcerative colitis(UC)by evaluating the pharmacological effects and network pharmacological mechanisms of Wumei Pills and its simplified prescription.Methods:The 2,4,6-trinitrobenzene sulfonic acid(TNBS)induced UC rats were used as the model.The colonic tissue damage,IL-1βand COX-2 levels were used to observe the treatment of Wumei Pills and its simplified prescription on UC rats.The effective components and its targets of Wumei Pills and its simplified prescription,and targets of UC were searched by the database.After taking the intersection,the network diagram of drug composition target disease was drawn.The protein interaction network of Wumei Pills and its simplified prescription acting on UC were constructed and the pathway analysis was performed.The molecular docking was used to verify the binding ability of the core components and core targets of Wumei Pills and its simplified prescription.Results The results of pharmacodynamic results showed that compared with the normal group of rats,the colon tissue of the model group was significantly thicker,the colon mass length ratio was significantly increased,and the levels of IL-1βand COX-2 in the colon tissue were increased.The difference was statistically significant(P<0.01).The intestinal tissue injury in the Wumei Pills group,the simplified prescription group and positive drug group were all improved.In the three groups,the colon mass length ratio was decreased,and the levels of IL-1βand COX-2 were also decreased.The difference was statistically significant(P<0.05).The network pharmacology showed that Wumei Pills and its simplified prescription has 111 and 99 targets respectively for UC.The topological analysis and pathway analysis found that the core targets and pathways of Wumei Pills and its simplified prescription on UC were similar.The molecular docking results showed quercetin,kaempferol and coptisine had strong binding ability to core targets.Conclusion:The results of pharmacodynamics and network pharmacology showed that the simplified prescription of Wumei Pills had feasibility for UC treatment.