The Millettia speciosa Champ polysaccharide attenuates pyroptosis by suppressing the signaling pathway of caspase-1/gasdermin D/Interleukin-1β

Abstract

Abstract Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Studies have shown that the Millettia speciosa Champ polysaccharide(MSP)has anti-inflammatory effects, but there is no report on whether the MSP has an effect on pyroptosis from the anti-inflammatory mechanism. This study aims to investigate the inhibitory effects of a water-soluble polysaccharide was obtained from Millettia Speciosa Champ(MSP-1)on the pyroptosis of RAW264.7 cells induced bylipopolysaccharide(LPS)/adenosine triphosphate(ATP). The results showed that MSP-1 significantly inhibited the pyroptosis of RAW264.7 macrophages. MSP-1 inhibited the secretions of IL-6, IL-1β, IL-18, nitric oxide (NO), and lactic dehydrogenase(LDH)and reduced caspase-1, cleaved IL-1β, and cleaved gasdermin D(GSDMD) activation of the cleaved protein levels. MSP-1 ameliorated the scorching of RAW264.7 macrophages by a mechanism that may be related to the downregulation of each of the caspase-1/IL-1β/GSDMD signaling pathways. In addition, the structure of MSP-1 was characterized in this study. MSP-1 consisted of only glucose with an average molecular weight of 50.2 kDa. Moreover, the infrared spectroscopy, methylation, and nuclear magnetic resonance (NMR) results showed that MSP-1 consisted of →4)-α-D-Glcp-(1→, →4, 6)-α-D-Glcp-(1→and T-α-Glcp.