Alleviation of sepsis-induced lung and liver injury by polysaccharides from Tetrastigma hemsleyanum Diels et Gilg via suppression of TLR4/NF-κB/COX-2 pathway and modulation of immune checkpoint molecules

Abstract

Sepsis, a common clinical complication, leads to multi-organ damage due to systemic infection and currently lacks effective therapeutic drugs. Polysaccharide derived from Tetrastigma hemsleyanum Diels et Gilg (TH), abbreviated as THP, is a water-soluble component extracted from TH, exhibiting anti-inflammatory and immunomodulatory properties. This study aims to investigate the effects and mechanisms of THP in sepsis. Results demonstrated that THP reduced neutrophils in the peripheral blood of mice established by cecal ligation and puncture (CLP), and inhibited IL-6 and MCP-1 in plasma, thereby improving systemic inflammation. THP ameliorated pulmonary edema, mitigated lung and liver histopathological injuries, reduced infiltration of neutrophils and macrophages in the lung and liver, and inhibited the TNF-α, IL-6, IL-1β, and MCP-1 transcription in both organs. Additionally, THP decreased myeloid cells, neutrophils, monocytes, and Tregs in the spleens of septic mice, while increasing T cells, CD4⁺ T cells, and CD8⁺ T cells, thereby restoring immune imbalance. Mechanistically, THP attenuated sepsis by inhibiting the overactivation of the TLR4/NF-κB/COX-2 pathway, and reducing PD-1, PD-L1, IDO1 in the lung, and PD-1, PD-L1 in the liver of septic mice. In conclusion, this study provides theoretical support for the potential application of THP in sepsis treatment.