Ginsenoside Rd ameliorates glucose metabolism by regulating GLP-1/ MAPK/ NF-κB signaling pathway in db/db mice

Background: Ginsenoside Rd shows positive effects on T2DM, but its mechanism is still unknown. We explore its mechanism from inflammation levels in pancreas and intestine, and provide some evidences that this is related to modulate GLP-1/MAPK/NF-κB signaling pathway. Methods: We recorded and compared the changes in metabolic indicators about T2DM, and tested levels of GLP-1 and GLP-1R through immunohistochemistry, Western blotting, and PCR after the mice were euthanized. Moreover, 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. At the same time, we conducted in vitro experiments to investigate GLP-1 signaling pathway. Results: After treatment with ginsenoside Rd, blood glucose decreased and insulin resistance weakened in db/db mice. The results showed an increase in the expression of GLP-1 and GLP-1R. Transcriptome analysis shows differences in inflammatory response related signaling pathways after treatment. Western blot results showed an increase in AMPK phosphorylation and a decrease in MAPK phosphorylation. Consistent experimental results were also obtained in vitro experiments. 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.