Abstract

Polygonum cuspidatum (P. cuspidatum) is an herbaceous perennial plant known as Asian knotweed that is used in Chinese medicine due to its active components. Recent studies of the uric acid-lowering activity of P. cuspidatum extracts have mainly focused on analysis of its crude extract or specific chemical components, with limited research about its uric acid-lowering activity in vivo. In present study, monomeric compounds with higher uric acid-lowering ability were isolated from P. cuspidatum extract by column chromatography and thin-layer chromatography (TLC) and tested in a hyperuricemia mouse model and xanthine oxidase (XOD) inhibition assay in vitro. Structural characterization of the isolated components was performed by nuclear magnetic resonance (NMR) spectroscopy and the potential mechanism of decreasing uric acid was analyzed using untargeted metabolomics. Two main novel compounds were isolated and identified, 1-(4-hydroxy-2-methoxyphenyl)-2-(4-hydroxy-3,5-dimethylphenyl)butane-1,2,3-triol (compound 1) and 1-(4-hydroxy-2-methoxyphenyl)-2-(4-hydroxy-3,5-dimethylphenyl)-3-methylbutane-1,2-diol (compound 2), and compounds 1 was proved more significant inhibitory effect on the activity of XOD (p < 0.01) with inhibition of 49.80%. Metabolomics analysis indicated that the fractions (compound 1 and compound 2) affected hyperuricemic mice mainly through changes in galactose metabolism (p = 5.74E-4) and the effects were closely related to metabolic pathways of organic acid, carbohydrate, and lipid metabolism. These results contribute to providing theoretical support for the utilization of P. cuspidatum as a food and medicinal material, which can increase its use as an alternative treatment for hyperuricemia.

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