Ginsenoside Rd Ameliorates Glucose Metabolism by Regulating GLP-1/MAPK/NF-κB Signaling Pathway in db/db Mice

Ginsenoside Rd shows positive effects on T2DM, but its mechanism remains unclear. In this study, we explored its mechanism focusing on inflammation levels in the pancreas and intestine, and provided evidence that this is related to modulation of the GLP-1/MAPK/NF-κB signaling pathway. We recorded and compared changes in metabolic indicators of T2DM, and tested levels of GLP-1 and GLP-1R through immunohistochemistry, Western blotting, and PCR after the mice were euthanized. Additionally, we detected the effects of ginsenoside Rd on inflammatory related molecules such as AMPK, Sirt1, MAPK, and NF-κB by ELISA, transcriptomics, Western blot, and PCR, while also conducting in vitro experiments to investigate the GLP-1 signaling pathway. After treatment with ginsenoside Rd, blood glucose decreased and insulin resistance weakened in db/db mice, and the results showed an increase in the expression of GLP-1 and GLP-1R. Transcriptome analysis revealed differences in inflammatory response-related signaling pathways after treatment, and Western blot results showed increased AMPK phosphorylation and decreased MAPK phosphorylation. Consistent experimental results were also obtained in vitro. In conclusion, our data suggest that ginsenoside Rd may ameliorate T2DM in db/db mice, potentially through the inhibition of inflammatory responses in the intestine and pancreas, an effect that might be mediated by the promotion of GLP-1 secretion.