Anti-inflammatory effects of Platycodin D on dextran sulfate sodium (DSS) induced colitis and E. coli Lipopolysaccharide (LPS) induced inflammation

Abstract

Platycodin D (PLD) is a saponin found in Platycodon grandiflorum, which has been reported to have anti-inflammatory effects. However, the effects of PLD on ulcerative colitis (UC) remain unknown. In this study, PLD showed the potential to reduce inflammation, ameliorate intestinal damage, and maintain intestinal integrity in DSS-induced colitis. However, the beneficial effect of PLD was reduced when macrophages were depleted, indicating the key role of macrophages in the beneficial effect of PLD in DSS-induced colitis. Meanwhile, we found that PLD inhibited the expression of M1 markers and promoted the expression of M2 markers in colon. Similarly, we found PLD significantly attenuated the levels of pro-inflammatory cytokines, increased the level of anti-inflammatory cytokine and altered macrophage proportions in LPS-stimulated RAW 264.7 cells in vitro. Moreover, treating LPS-stimulated RAW 264.7 cells with PLD increased the activation of the PI3K/Akt signaling pathway and decreased activation of NF-κB pathway. Furthermore, we found that the anti-inflammatory and macrophage polarization regulatory effects of PLD was Adenosine 5′-monophosphate-activated protein kinase (AMPK)-dependent. These results indicate that PLD attenuates DSS-induced colitis and LPS-induced inflammation, and the mechanism behind the phenomenon may be regulating macrophage polarization via activation of AMPK. Our study provides a theoretical basis for PLD to be used as a potential treatment of colitis.