Ganoderma lucidum Polysaccharides Alleviate Diabetic Cardiomyopathy Structural Deficits and Remodeling by Attenuating Inflammatory Responses

Background: Diabetes is the one of the most prevalent chronic diseases worldwide and poses a serious danger to human health, following cancer and cardiovascular and cerebrovascular diseases. Diabetic cardiomyopathy (DCM) is a leading cause of death among individuals with diabetes. Ganoderma lucidum polysaccharides (GLPs) are among the principal bioactive components in the fruiting bodies of Ganoderma lucidum, and are characterized by complex structures and a range of pharmacological properties. In several studies, GLPs have been shown to exert hypoglycemic effects and to help normalize dysregulated glucose metabolism. Our team has also previously demonstrated the ability of GLPs to inhibit cardiac hypertrophy induced by increased cardiac afterload. However, systematic investigations ofthe effects of GLPs in DCM remain limited, and the molecular mechanisms through which GLPs shape DCM pathogenesis remain unclear. Methods: We investigated the effects of Ganoderma lucidum polysaccharides (GLPs) on diabetic cardiomyopathy (DCM) in mouse models of streptozotocin-induced type 1 diabetes mellitus (T1DM) and high-fat diet-induced type 2 diabetes mellitus (T2DM). Results: We found that GLPs exerted therapeutic effects in murine models of both T1DM and T2DM. RNA-seq analysis suggested that the anti-inflammatory of GLPs involve nuclear factor-kappa B (NF-κB) signaling. Cardiac inflammation is a key pathological process in DCM, and GLP treatment attenuated cardiac functional and structural abnormalities while reducing cardiac inflammation, fibrosis, and NF-κB signaling. GLP administration further reduced DCM-associated increases in pro-inflammatory cytokines and macrophage infiltration in T1DM and T2DM mice. In vitro, GLPs suppressed high glucose (HG)-induced cardiac hypertrophy and fibrosis, and the protective effects of GLPs were associated with NF-κB signaling. Conclusions: Collectively, our findings demonstrate that GLPs effectively alleviate DCM and cardiac remodeling and the protective effects of GLPs are involved in NF-κB signaling. Our data suggest that GLPs may serve as a potential therapeutic agent for the treatment of DCM.