A structurally characterized water-soluble galactoglucomannan from Poria cocos alleviates rheumatoid arthritis by regulating the JAK2/STAT3 and NF-κB signaling pathways.

Current treatments for rheumatoid arthritis (RA), a chronic autoimmune disorder, are associated with several negative side effects, necessitating the development of safer alternative treatments. In this study, we focus on Poria cocos (Schw.) Wolf, a homologous fungus traditionally used as a functional ingredient in East Asian cuisine and traditional medicine. The water-soluble heteropolysaccharide PCP70-2-1, which has an average molecular weight of 13 kDa, was obtained from the sclerotium of P. cocos, and its structure was characterized through monosaccharide composition, partial acid hydrolysis, methylation, nuclear magnetic resonance spectroscopy, and morphological analyses. Structural analysis revealed that PCP70-2-1 is composed of mannose, glucose, galactose, and fucose, while its backbone comprises →2)-α-D-Manp-(1→3,6)-α-D-Manp-(1→ and branches at the O-3 position of the backbone. The anti-RA mechanisms of PCP70-2-1 were systematically evaluated in lipopolysaccharide-induced MH7A cells. The results demonstrated that PCP70-2-1 significantly suppressed MH7A cell proliferation and migratory capacity, downregulated the mRNA expression of proinflammatory cytokines (i.e., IL-6, IL-8, and IL-1β), and promoted apoptosis by inducing mitochondrial membrane potential depolarization and modulating the expression of BAX and BCL2. Mechanistic investigations revealed that PCP70-2-1 alleviated RA by regulating the JAK2/STAT3 and NF-κB signaling pathways. In conclusion, PCP70-2-1 is a promising preventive candidate for RA therapeutics, supporting its use in P. cocos-derived nutraceuticals for early inflammation control.