Dendrobium officinale polysaccharide inhibits M1 macrophage polarization via activating SENP1-SIRT3 signaling and alleviates ulcerative colitis

Macrophage polarization is closely associated with the onset and progression of various diseases, including ulcerative colitis (UC). Previous studies have demonstrated that Dendrobium officinale polysaccharides (DOPS) exert a significant anti-inflammatory effect. However, the potential of DOPS to suppress inflammation by regulating macrophage polarization has not yet been reported. In this study, we aimed to investigate the effects of DOPS on macrophage polarization and to elucidate the underlying mechanisms. Our findings indicate that DOPS significantly promotes the polarization of macrophage from the M1 to the M2 phenotypes. Further research revealed that DOPS notably shifts the metabolic reprogramming of activated macrophages via suppressing glycolysis. Mechanistically, we discovered that DOPS primarily relies on activating SENP1-SIRT3 axis to regulate both the polarization and metabolic functions of activated macrophages. In vivo experimental results indicate that DOPS can promote the polarization of macrophages from M1 to M2 in the colonic tissue of UC mice, while also inhibiting the levels of glycolytic metabolic indicators in these mice, including glucose uptake, lactate dehydrogenase activity and lactate production. Importantly, DOPS can significantly inhibit the expression of proteins and genes within the SENP1-SIRT3 axis in UC mice. In summary, these results suggest that DOPS promotes the polarization of macrophage from the M1 to the M2 phenotypes through the activation of the SENP1-SIRT3 axis to inhibit macrophage glycolysis, thereby exerting its anti-inflammatory effects.