The acetylation of Ganoderma applanatum polysaccharides on ameliorating T2DM-induced hepatic and colonic injuries by modulating the Nrf2/keap1-TLR4/NFκB-Bax/Bcl-2 pathways.

It was imperative to discover and utilize high-efficiency, non-toxic substances for the prevention and management of type 2 diabetes mellitus (T2DM) and its associated complications, given the escalating prevalence and significant global health burden. In the present study, the acetylated Ganoderma applanatum polysaccharide (A-GAP) was successfully obtained and characterized, demonstrating excellent efficacy in ameliorating organ damage induced by T2DM through targeted modulation of the gut-liver axis. The physiological and molecular biological findings indicated that A-GAP may modulate the Nrf2/Keap1-TLR4/NFκB-Bax/Bcl-2 signaling pathway network, thereby mitigating oxidative stress and the subsequent inflammatory response, ultimately alleviating the inhibitory effects of IRS and insulin resistance. Besides, the regulatory impact of A-GAP on the gut-liver axis had been confirmed by its ability to maintain intestinal barrier integrity and increase levels of intestinal tight junction proteins, effectively preventing endotoxin translocation to the liver. This discovery highlighted the potential of A-GAP as a promising option for functional or nutritional foods and pharmaceuticals in managing T2DM and its complications, showcasing the significance of acetylation in enhancing the bioactivities of natural substances.