Ganoderma Lucidum polysaccharide peptide (GL-PP2): A potential therapeutic agent against sepsis-induced organ injury by modulating Nrf2/NF-κB pathways.

Sepsis, characterized by a severe immune response to infection, remains a leading cause of mortality, with few effective strategies to prevent organ damage. Targeting inflammation, oxidative stress, and apoptosis is crucial for improving outcomes and advancing sepsis management. We investigated the protective effects of Ganoderma Lucidum Polysaccharide Peptide 2 (GL-PP2) against sepsis-induced organ damage, focusing on immune regulation and kidney protection. In a murine sepsis model, mice received intraperitoneal injection of GL-PP2 (25, 50, 100 mg/kg) for seven days, with dexamethasone (5 mg/kg) as a positive control. Sepsis was induced by intraperitoneal lipopolysaccharide (LPS, 10 mg/kg), followed by histological, biochemical, molecular, and network pharmacology analyses to evaluate kidney and spleen damage. Results demonstrated that GL-PP2 mitigates LPS-induced kidney and spleen damage, preserving tissue integrity and improving renal function markers (blood creatinine, urea nitrogen). GL-PP2 also lowers pro-inflammatory cytokines, boosts antioxidant enzymes, and modulates the Nrf2/NF-κB pathways, highlighting its anti-inflammatory and antioxidant effects. Additionally, it reduces apoptosis by regulating Bax, cleaved caspase-3, and Bcl-2 expression. These findings indicate that GL-PP2 is a promising sepsis therapy candidate, as it targets inflammation, oxidative stress, and apoptosis, reducing organ injury. By modulating key pathways, GL-PP2 could improve clinical outcomes, warranting further study.