Network pharmacology, molecular docking and experimental validation to elucidate the anti-T2DM mechanism of Lanxangia tsaoko.

Lanxangia tsaoko (L. tsaoko) is a natural medicine which could be used to treat type 2 diabetes mellitus (T2DM). However, there is no systematic and comprehensive research on the its active compounds and mechanism. This study aimed to investigate the active ingredients and potential mechanism of L. tsaoko for the treatment of T2DM. The chemical constituents of L. tsaoko were identified by UPLC-Q-Exactive Orbitrap/MS. The active compounds and mechanism of L. tsaoko were predicted by network pharmacology. Then the docking modes of key components and core targets were analyzed by molecular docking. Finally, animal experiments were conducted to verify the efficacy and targets of L. tsaoko in T2DM treatment. 70 compounds from L. tsaoko were identified. We obtained 37 active components, including quercetin, genistein and kaempferol, 5 core targets were AKT1, INS, TP53, TNF and IL-6. Mainly involved in PI3K/Akt, MAPK, RAGE/AGE, HIF-1, FoxO signaling pathways. Molecular docking results showed that the L. tsaoko had good binding potential to TNF. Therefore, we took the inflammatory mechanism as the prediction target for experimental verification. Animal experiments showed that L. tsaoko could alleviated colon injury of T2DM mice, improve glucose metabolism and decrease inflammatory levels. L. tsaoko exerted therapeutic effects on T2DM through multi-component, multi-target and multi-pathway regulation. Its action mechanisms were related to PI3K/Akt, MAPK, RAGE/AGE, HIF-1 and FoxO signaling pathways. This study provided new insights for the clinical treatment of T2DM.