Structural characterization of a fermentation-produced pectic polysaccharide from Astragalus membranaceus and its mechanistic role in alleviating hyperuricemia via mitochondrial homeostasis.

FAPS-C1, the novel pectic polysaccharide with excellent hypouricemic activity, was screened during a 28-day fermentation of Astragalus membranaceus for in vitro uric acid-lowering activity in HK-2 cells. The structure analysis results indicated that the major monosaccharide composition of FAPS-C1 consisted of arabinose (Ara), galacturonic acid (GalA), galactose (Gal), mannose (Man), glucose (Glc), and rhamnose (Rha) in a molar percentage of 26.582: 27.585: 12.789: 12.679: 7.345: 2.603. The molecular weight of FAPS-C1 was 5462 Da. FAPS-C1 was identified as homogalacturonan (HG) containing short rhamnogalacturonan-I (RG-I) regions. The main chain of FAPS-C1 was composed of →4)-α-GalpA-(1→ repeating units, interspersed with→2)-α-Rhap-(1→ residues. In vitro experiments demonstrated that FAPS-C1 (5 μM) significantly (p < 0.05) decreased uric acid levels in XOD-induced HK-2 cells. Mechanistic investigations indicated that FAPS-C1 may activate the PGC-1α/DRP1/NRF1/TFAM/Cyt.C signaling pathways, thereby modulating the mitochondrial dynamics network and significantly reducing uric acid levels. Furthermore, in vivo pharmacokinetic analysis revealed that fluorescein isothiocyanate-labeled FAPS-C1 reached a relatively late peak time. Biodistribution studies suggested that FAPS-C1 predominantly accumulated in the colon, small intestine, and kidneys, supporting the notion that this macromolecular compound was poorly absorbed and that the kidney was an important target organ for FAPS-C1. In conclusion, FAPS-C1, a novel pectin-like polysaccharide from fermented Astragalus membranaceus, holds potential as a therapeutic agent for hyperuricemia.