The polysaccharides from mixed-culture fermentation of huangjing: extraction, structural analysis and anti-lipid activity

Huangjing (Polygonatum sibiricum) is a traditional medicinal and edible plant which requires processing, such as fermentation, to mitigate irritability and enhance functionality. During the fermentation, microorganisms will alter the structure and efficacy of polysaccharides. This study compared polysaccharides from aqueous extraction (AEPSP) and yeast-Rhizopus fermentation (FBPSP) to evaluate structural and bioactivity differences. FBPSP exhibited a complex monosaccharide profile dominated by D-galactose (26.58%), glucose (25.43%), and D-galacturonic acid (22.39%), contrasting with AEPSP’s glucose-rich composition (31.03%). Structural analyses revealed that FBPSP had higher thermal stability, larger molecular weight (13.0 kDa), and more rough morphology, which attributed to microbial glycometabolism. In vitro, FBPSP significantly reduced lipid accumulation in HepG2 cells by 27% and downregulated triglyceride, cholesterol, and low density lipoprotein (LDL-c) levels.The results of western blot revealed that FBPSP modulated lipid metabolism via peroxisome proliferators-activated receptor alpha/ platelet glycoprotein 4 (PPARα/CD36) suppression and carnitine palmitoyltransferase 1 (CPT-1) activation. Transcriptomics analysis highlighted tumor necrosis factor (TNF) and janus-activated kinase singal transducers and activators of transcriprion (JAK-STAT) pathways as potential regulatory targets. These findings demonstrate fermentation as a superior method to enhance huangjing polysaccharides’ bioactivity, offering a sustainable alternative to traditional processing for managing lipid-related disorders. • Enhanced bioactivity through fermentation: Yeast-Rhizopus fermentation significantly altered the monosaccharide composition of Polygonatum sibiricum polysaccharides (FBPSP), enriching D-galactose, D-xylose, and D-galacturonic acid, which are linked to improved antioxidant and anti-lipid properties. • Superior thermal stability of FBPSP: Fermented polysaccharides exhibited higher thermal resistance compared to aqueous-extracted polysaccharides (AEPSP), suggesting better structural integrity and functional retention under high-temperature processing. • Mechanistic insight into lipid inhibition: FBPSP reduced lipid accumulation in HepG2 cells by suppressing fatty acid uptake (via CD36 downregulation) and enhancing mitochondrial β-oxidation (via CPT-1 activation), effectively lowering triglyceride, cholesterol, and LDL-c levels. • Transcriptome-driven pathway discovery: RNA-seq analysis revealed that FBPSP modulated lipid metabolism through TNF and JAK-STAT signaling pathways, highlighting its potential for targeting metabolic disorders at the molecular level.