Abstract:
Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.
摘要:
绞股蓝(Thunb。)牧野(GP),一种药食同源的植物,作为中药,在预防和治疗2型糖尿病(T2DM)方面具有很好的生物学活性。然而,GP治疗T2DM的物质基础和作用机制尚未完全阐明。本研究旨在阐明活性成分,GP治疗T2DM的潜在靶点和信号通路。采用UPLC-HRMS分析和文献研究相结合的方法收集GP的化学成分。网络药理学显示,GP在治疗T2DM中有32种成分和326个潜在靶点。结果显示GP通过介导胰岛素抵抗信号通路影响T2DM,PI3K/Akt信号通路和FoxO1信号通路,与T2DM关系密切。分子对接结果显示,STAT3、PIK3CA、AKT1,EGFR,VEGFA和INSR与GP活性化合物具有较高的亲和力。体外,GP提取物明显增加IR-HepG2细胞的葡萄糖摄取和葡萄糖消耗。GP提取物增加了PI3K的水平,p-AKT,p-GSK3β和p-FoxO1的表达降低了p-IRS1、p-GS、PEPCK和G6Pase,这表明GP可以通过调节IRS1/PI3K/Akt信号通路促进糖原合成和抑制糖原异生。结果表明,GP可以通过调节IRS1/PI3K/Akt信号通路,促进葡萄糖摄取和糖原合成,抑制糖异生,从而改善胰岛素抵抗。这可能是T2DM的潜在替代疗法。