Mechanism of Trigonella Foenum-graecum L. against Type 2 Diabetes Mellitus: Research on Network Pharmacology & Experimental Verification

Objective: The aim of this study was to explore the mechanisms of Trigonella foenumgraecum L. (T. foenum-graecum) in the treatment of type 2 diabetes mellitus (T2DM). Methods: The TCSMP database was utilized to obtain the constituents and targets of T. foenumgraecum. The OMIM database was used at GeneCard to acquire T2DM targets. The STRING database was used to plot the PPI network. KEGG and GO analyses were performed using the DAVID database. HepG2 cells were induced to construct an insulin resistance (IR) model by a complex composed of glucose and oleic acid, and cell viability, inflammatory factors, and RAGE/PI3K/Akt signaling pathway were verified by in vitro cell experiments. Results: In the network pharmacology study, 14 active ingredients were screened, corresponding to 280 targets. There were 1477 targets associated with T2MD. These components may act on core targets of T2DM, such as AKT1, TNF, and IL-6, and regulate signaling pathways such as cancer pathway and AGE-RAGE to play an anti-T2DM role. In vitro results showed that quercetin and kaempferol with 5, 10, 25 μmol·L-1 and diosgenin with 0.5, 1, 2 μmol·L-1 could reduce the expression of TNF-α and IL-6 in IR-HepG2 cells, down-regulate the expression of RAGE, up-regulated the expression of p-PI3K/PI3K and p-Akt/Akt. Conclusion: The research explored the mechanism of T. foenum-graecum anti-T2DM, which may be helpful for the development of anti-T2DM drugs for T. foenum-graecum.