Structural characterization of polysaccharide isolated from Inonotus hispidus and its anti-obesity effect based on regulation of the interleukin-17-mediated inflammatory response.

A heteropolysaccharide (IHP3) with a molecular weight of 22.0 kDa was isolated from Inonotus hispidus (Bull.: Fr.) P. Karst using column chromatography purification from water extraction. Its backbone was predominantly composed of →6)-α-D-Galp-(1→, →2,6)-α-D-Galp-(1→,→6)-α-D-O-Me-Galp-(1→, →3)-α-D-Manp-(1→, and →3,4,6) -β-D-Galp-(1→ residues, branched at C2 of partial α-D-Galp, or C3 and C4 of β-D-Galp, and terminated by α-D-Manp, and α-L-Fucp. In high-fat diet (HFD)-fed obese mice, IHP3 effectively suppressed body weight and plasma glucose gain, decreased fat accumulation, ameliorated lipid metabolism, and protected liver function from HFD-induced damage. Combining the analysis of gut microbiota metabolomics, hepatic proteomics and biochemical detection revealed, IHP3 significantly altered cecum fecal metabolite abundances, inhibited the phosphorylation of peroxisome proliferator-activated receptor gamma, and promoted the browning of white adipose tissue and the activation of brown adipose tissue. These changes collectively contributed to alleviating obesity symptoms by suppressing the interleukin (IL)-17-mediated inflammatory response in obese mice. Therefore, these findings suggest that IHP3 could be a potential candidate for the development of anti-obesity drugs.