Lipid-lowering effects of bile Arisaema polysaccharides on high-fat diet-induced hyperlipidemia: An integrated analysis of metabolomics, lipidomics and microbiome.

Bile Arisaema, a traditional Chinese medicine, has been previously identified by our team to possess antipyretic properties attributed to its polysaccharide component. Recently, we have confirmed that bile Arisaema played a significantly lipid-lowering effect on hyperlipidemia rats. Building upon this discovery, the present study aimed to investigate the unexplored hypolipidemic potential of its polysaccharide component and elucidate the underlying mechanisms. A soluble polysaccharide fraction devoid of free proteins, named BAPs, was extracted from bile Arisaema using a combination of hot water extraction, alcohol precipitation, and the Sevage method. The structural characteristics of BAPs were preliminarily elucidated through monosaccharide composition analysis (mainly composed of glucose), molecular weight distribution (38.74 kDa and 2.87 kDa), and glycosyl linkage analysis via methylation. The results of animal experiment demonstrated that oral administration of BAPs (400 mg/kg/day) for four weeks significantly improved abnormal serum lipid levels, hepatic function and histopathological injury on high-fat diet-induced hyperlipidemia rats. Mechanistically, the results of high throughput sequencing indicated that BAPs intake markedly altered the hepatic and fecal metabolome and lipidome, while also modulating gut microbiota composition and improving intestinal barrier integrity. Spearman's correlation analysis unveiled closely associations between the altered microbes, lipids, metabolites and serum biochemical indicators. Western blotting and qRT-PCR analyses further confirmed that these metabolic improvements were mediated by the regulation of key genes involved in lipid metabolism. Collectively, this study demonstrated that BAP supplementation effectively improved serum lipid profiles in hyperlipidemia rats by modulating metabolic disorders and restoring gut homeostasis.