Paeoniflorin inhibited macrophage polarization via glycolysis pathway to protect against sepsis-induced intestinal injury

Sepsis, a severe immune response to infection, can cause life-threatening damage to organs, including the intestines. Researchers investigated whether the compound paeoniflorin, known for its anti-inflammatory properties, could protect against intestinal injury in sepsis by targeting macrophage glycolysis. Male mice were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis.

After administering paeoniflorin intraperitoneally, the mice showed increased survival rates. Blood tests revealed lower levels of inflammatory markers in the treated mice, and intestinal histology showed reduced damage. Paeoniflorin also promoted M2 macrophage polarization and decreased M1 macrophages in the intestine. Transcriptomic analysis confirmed that paeoniflorin rectified abnormal glycolysis and gluconeogenesis.

However, the compound's protective effects were diminished when combined with TEPP-46, a PKM2 activator. TEPP-46 treatment reversed the protective effects of paeoniflorin, leading to increased intestinal damage and inflammation. The researchers concluded that paeoniflorin protects against sepsis-induced intestinal injury by regulating macrophage glycolysis, maintaining a balance between M1 and M2 polarization, and preserving intestinal barrier function.