基于网络药理学和分子对接技术探讨黄芪桂枝五物汤治疗糖尿病周围神经病变和类风湿性关节炎“异病同治”的作用机制

Exploration of the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of diabetic peripheral neuropathy and rheumatoid arthritis‘treating different diseases together’based on network pharmacology and molecular docking technology

目的 运用网络药理学方法和分子对接技术,从益气活血的角度探讨黄芪桂枝五物汤治疗糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)和类风湿性关节炎(rheumatoid arthritis, RA)“异病同治”的作用机制。方法 本研究运用网络药理学,从中医“同治异病”的角度探讨黄芪桂枝五物汤治疗DPN、RA的作用机制。结果 黄芪桂枝五物汤治疗DPN、RA都采用了益气温经、和血通痹的治疗方法,证实了DPN、RA在其证候特点的相同点,也推出了两者“异病同治”的客观存在性。黄芪桂枝五物汤对DPN和RA的治疗作用主要是通过整体调控晚期糖基化终末产物(advanced glycosylation end products, AGEs)—糖基化终末产物受体(receptor of AGEs, RAGE)信号通路实现的,但对不同病变有不同的侧重点。DPN的治疗主要通过抑制神经元凋亡和刺激突触再生来保护神经。RA的治疗往往依赖于对肿瘤坏死因子(transforming necrosis factor, TNF)信号通路、Toll样受体(Toll-like receptors, TLRs)信号通路、白介素17(interleukin 17,IL-17)信号通路等炎症相关通路的调节,以减少炎性因子,调节免疫。结论 黄芪桂枝五物汤可通过相同途径和不同途径治疗DPN、RA,两者虽有相通之处和内在联系,但也有不同之处,故应着眼于不同的方向,为研究提供新的启示。

Objective Using network pharmacology methods and molecular docking techniques,the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of diabetic peripheral neuropathy(DPN)and rheumatoid arthritis(RA)was investigated in terms of benefiting qi and activating blood.Methods In this study,the network pharmacology was used to explore the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of DPN and RA from the perspective of“treating different diseases with the same treatment”in traditional Chinese medicine.Results The treatment of DPN and RA with Huangqi Guizhi Wuwu Decoction both adopts the treatment method of benefiting qi and warming meridian,and harmonizing blood and dredging bi,which not only confirms the similarities of the DPN and RA in their syndrome characteristics,but also promotes the objective existence of the principle of“treating different diseases with the same treatment”.Huangqi Guizhi Wuwu Decoction’s therapeutic effects on DPN and RA are mainly achieved through the overall regulation of AGE-RAGE signaling pathway in diabetic complications,but it has different focuses on different lesions.DPN mainly protects the nerves by inhibiting neuronal apoptosis and stimulating synaptic regeneration.The treatment of RA often relies on the regulation of inflammation-related signaling pathways such as TNF signaling pathway,IL-17 signaling pathway,and Toll-like receptor signaling pathway to reduce inflammatory factors and regulate immunity.Conclusion The treatment of DPN and RA by Huangqi Guizhi Wuwu Decoction can be achieved through the same and different pathways,and although the two similar and intrinsically linked,they are also different and should be approached in different directions to provide new insights for research.