Protective effects of Ganoderma lucidum polysaccharide peptides against cisplatin-induced toxicity

Abstract

Ethnopharmacological relevance: Ganoderma lucidum (G. lucidum) has been used in traditional Chinese medicine for centuries to enhance vitality and support organ function. It has been traditionally used to manage chronic inflammation, fatigue, and toxin-induced organ injury. Its polysaccharide-rich extracts possess immunomodulatory and antioxidant properties, attracting growing interest in kidney protection research.

Aim of the study: To investigate the protective effects of G. lucidum polysaccharide peptide (GL-PP) and G. lucidum polysaccharide peptide 2 (GL-PP2) against cisplatin (CDDP)-induced multi-organ toxicity and to explore their underlying mechanisms.

Materials and methods: Both in vivo and in vitro models were employed in this study. Key markers, including biochemical indices, histological changes, oxidative stress parameters, inflammatory cytokines, fibrotic factors, and apoptotic proteins, were systematically evaluated. Mechanistic investigations employed network pharmacology prediction and Western blotting analysis to elucidate the underlying mechanisms of action.

Results: GL-PP and GL-PP2 ameliorated cardiac, hepatic, and renal function by attenuating CDDP-induced elevations in related enzymes and metabolites, and mitigated histopathological damage and fibrosis in these tissues. Specifically, GL-PP2 (200 mg/kg) exerted anti-inflammatory and antioxidant effects by activating the protein kinase B/glycogen synthase kinase-3 beta/nuclear factor erythroid 2-related factor 2 signaling pathway. Additionally, it regulated the expression of key apoptosis-related proteins, including B-cell lymphoma-2-associated X protein, B-cell lymphoma-2, and cleaved caspase-3.

Conclusion: GL-PP and GL-PP2 confer multi-organ protection against CDDP-induced toxicity primarily by activating the protein kinase B/glycogen synthase kinase-3 beta/nuclear factor erythroid 2-related factor 2 signaling pathway, with GL-PP2 exhibiting superior efficacy.

Keywords: AKT/GSK3β/Nrf2 pathway; Cisplatin-induced nephrotoxicity; Ganoderma lucidum polysaccharide peptide; Ganoderma lucidum polysaccharide peptide 2; Multi-organ protection.