Suppressive activities of lupeol on sepsis mouse model

Abstract

Sepsis is a life-threatening condition triggered by the body’s extreme response to an infection, leading to widespread inflammation, organ dysfunction, and potentially fatal complications. While lupeol, a significant phytosterol found in various herbal plants, has been considered as a potential anti-cancer agent, its anti-septic activities and underlying molecular mechanisms remain unclear. The aim of this study is to investigate the effects of lupeol on a cecal ligation and puncture (CLP)-induced septic mouse model. Animals were categorized into six groups: control, CLP-operated, CLP plus maslinic acid, and CLP plus lupeol (0.5, 1, or 2 mg/kg). The assessment included survival rate, body weight changes, inflammatory cytokines, and histological analyses. Additionally, human endothelial cells were stimulated with high mobility group box1 (HMGB1) protein and lupeol, with cell viability determined. Inflammatory markers and gene expression were evaluated through enzymelinked immunosorbent assay and Western blot analysis, respectively. After CLP surgery, the group treated with lupeol showed improved survival rates and body weight compared to the untreated control group. Lupeol treatment also decreased levels of tumor necrosis factor (TNF)-α, interleukin-1β, nitric oxide, and cytokines associated with kidney inflammation. When administered to HMGB1-activated cells, lupeol reduced the expression of Toll-like receptor 4 and TNF-α, while simultaneously activating phosphoinositide 3-kinase/AKT signaling to enhance cell survival. In conclusion, lupeol demonstrated anti-inflammatory properties and conferred protective effects against CLP-induced sepsis, reinforcing cell survival in the face of septic responses.