鸡血藤治疗糖尿病周围神经病变的网络药理学研究及机制探讨

Mechanism of Spatholobi Caulis in diabetic peripheral neuropathy based on network pharmacology

目的采用网络药理学及分子对接技术探究鸡血藤治疗糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的活性成分及机制。方法基于TCMSP、GeneCards、String、Uniprot等数据库获取鸡血藤活性成分及DPN靶点,利用GO、KEGG数据库进行功能富集分析,对预测的关键活性化合物和靶点进行分子对接实验。使用UPLC-MS/MS测定鸡血藤水提物化学成分,结合网络药理学推测鸡血藤对DPN可能发挥作用的成分,并通过细胞实验验证鸡血藤活性成分芒柄花黄素对高糖环境下雪旺细胞的保护作用。结果鸡血藤治疗DPN的可能机制是通过作用于白细胞介素6(interleukin 6,IL-6)、信号传导转录激活因子3(signal transducer and activator of transcription 3,STAT3)等靶点影响DPN的AGE-RAGE信号通路,黄酮类化合物是其发挥疗效的物质基础。鉴定出鸡血藤水提物中9种化学成分,包括芒柄花黄素、芒柄花苷等。细胞实验证实芒柄花黄素通过抑制STAT3-NFκB信号通路减轻高糖引起的雪旺细胞(schwann cell,SCs)炎症反应,减少SCs凋亡,具有抗DPN的潜力。结论鸡血藤中以芒柄花黄素为代表的黄酮类成分可能通过抑制AGE-RAGE通路中的炎症反应治疗DPN。

Objective The active components and mechanism of Spatholobi Caulis in the treatment of diabetic peripheral neuropathy(DPN)were explored by the network pharmacology and molecular docking technology.Methods The active components of Spatholobi Caulis and DPN targets were obtained based on TCMSP,GeneCards,String and Uniprot databases,then functional enrichment analysis was performed on GO and KEGG databases.Molecular docking experiments were carried out between the predicted key active compounds and targets.Next,the chemical constituents of Spatholobus Caulis water extraction were analyzed by UPLC-MS/MS system and combined with the results of network pharmacology,the active components were speculated.As for experiments,the protective effects of formononetin,the representative component of Spatholobus Caulis,on Schwann cells in high glucose environment were investigated.Results The results showed that Spatholobus Caulis mainly affected AGE-RAGE signaling pathway in diabetes and its flavonoids were the material basis in the treatment of DPN.9 chemical components including formononetin,ononin,were detected in the water extract of Spatholobus Caulis by UPLC-MS/MS.In vitro experiments,it was found that formononetin could reduce the inflammatory response and apoptosis in Schwann cells induced by high glucose by inhibiting STAT3-NFκB signaling pathway.Conclusion Spatholobus Caulis played a role in DPN treatment probably by inhibiting the inflammatory response in AGE-RAGE signaling pathway and its effective components were flavonoids represented by formononetin.