Ganoderma lucidum polysaccharide peptide (GLPP) attenuates rheumatic arthritis in rats through inactivating NF-B and MAPK signaling pathways

Background: Not many drugs with fewer side effects are available for the treatment of rheumatoid arthritis (RA). Ganoderma lucidum polysaccharide peptide (GLPP) has good immunomodulatory effects, but whether it is effective in managing RA is not clear. Purpose: This study was conducted to examine the anti-RA activity and possible mechanisms of GLPP in collageninduced arthritis (CIA) rats. Methods: Male Wistar rats were intradermally injected with bovine type II collagen in the tail base to establish the CIA model and were orally administered 100 or 200 mg/kg GLPP for 35 days. Paw thickness, clinical arthritis scores, gait analysis, organ index determination, blood cell counts, micro-CT imaging and pathological staining were performed on the rats. Liver and kidney function were measured by commercial kits, and antibody levels were measured by ELISA kits. RA-related protein levels were detected by Western blotting. Results: GLPP effectively alleviated CIA symptoms and reduced immune organ indexes, antibody levels and systemic organ injury. GLPP decreased the protein expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, matrix metalloproteinase (MMP)2, MMP9, MMP13, BCL-2, OPN, beta-Catenin, and hypoxia inducible factor (HIF)-1 alpha and increased the protein expression of BAX in the joint tissues of CIA rats. Moreover, GLPP decreased the phosphorylation levels of p65, I kappa B-alpha and ERK1/2. Conclusion: GLPP effectively alleviated RA symptoms in CIA rats by inhibiting the NF-kappa B and MAPK pathways. This study suggests a promising therapeutic effect of mushroom-derived polysaccharide peptides on RA.