# The Molecular Mechanism of Polysaccharides from Polygonatum cyrtonema Hua in Improving Hyperuricemia by Regulating Key Targets of Uric Acid Metabolism in Mice

## TL;DR

This study shows how polysaccharides from Polygonatum cyrtonema Hua reduce high uric acid levels in mice by targeting key metabolic pathways and inflammation.

## Contribution

The first demonstration of PCPs' anti-hyperuricemic effects and their molecular mechanisms in mice.

## Key findings

- PCPs significantly reduced serum uric acid and xanthine oxidase activity in hyperuricemic mice.
- PCPs downregulated urate transporter 1 and reduced inflammatory cytokines like IL-1β and TNF-α.
- Galactose residues in PCPs formed strong hydrogen bonds with XOD and URAT1, improving target regulation.

## Abstract

Polygonatum cyrtonema Hua, a plant with a long history of consumption in China, serves both medicinal and edible purposes, and it exhibits numerous pharmacological effects, including promoting kidney health and enhancing immune function. However, the effect and molecular mechanism of Polygonatum cyrtonema polysaccharides (PCPs) on hyperuricemia have not yet been reported. The hyperuricemic mice model was induced by the intraperitoneal injection of potassium oxonate (PO, 300 mg/kg), combined with the intragastric administration of hypoxanthine (HX, 300 mg/kg). Biochemical assays in mice revealed that PCPs markedly lowered high serum uric acid levels, suppressed xanthine oxidase (XOD) activity, and reduced the expression of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Western blot analysis demonstrated that PCPs downregulated urate transporter 1 (URAT1), while H&E staining showed that PCPs effectively restored renal histological integrity. Here, we isolated and identified the PCPs, which consist mainly of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with a molar mass ratio of 0.5:2.15:0.47:16.58:3.66:1.09. Furthermore, the galactose residue that docked with both XOD and URAT1 molecules forms more hydrogen bonds and exhibits a lower binding energy, which enables the improved regulation of both targets. We have demonstrated for the first time the improving effect of PCPs on hyperuricemia, and revealed their regulatory mechanisms by modulating xanthine oxidase, inflammatory factors, and uric acid transporters. This study not only provides new insights into the anti-hyperuricemic activity of PCPs in mice, but also lays a foundation for its potential application in the functional foods of anti-hyperuricemia.