Characterization of xanthine oxidase inhibitory activities of phenols from pickled radish with molecular simulation

Pickled radish is a general source of natural bioactive compounds that include Phenols. Here, we used molecular docking, fluorescence quenching, circular dichroism spectroscopy and molecular dynamics simulations to identify potential inhibitors against Xanthine Oxidase from a library of pickled radish compounds. The most effective compounds were selected for validation through in vitro experiments including enzyme activity inhibition tests, and cell-based assays. Molecular docking results revealed that 2,6-Dihydroxyacetophenone, 4-Hydroxyphenethyl alcohol, and 4-Hydroxybenzaldehyde exhibited significant effects on Xanthine Oxidase inhibition. Three Phenols have varying degrees of inhibition on Xanthine Oxidase, which is driven by hydrophobic interactions and hydrogen bonds and affects the secondary structure and hydrophobic homeostasis of Xanthine Oxidase. The stability of Xanthine Oxidase inhibition by three Phenols was analyzed by molecular dynamics simulation. Finally, cellular experiments confirmed that three Phenols reduced uric acid levels by inhibiting the Xanthine Oxidase enzyme activity of BRL 3A cells.

1-Monopalmitin (PubChem CID: 14900); 2,6-Dihydroxyacetophenone (DHAP, PubChem CID: 69687); 4-Hydroxybenzaldehyde (HBA, PubChem CID: 126); 4-Hydroxyphenethyl alcohol (4-HPEA, PubChem CID: 10393); 5-Hydroxymethylfurfural (5-HMF, PubChem CID: 237332); Allopurinol (AP, PubChem CID: 135401907); BRL 3A cell; Carvacrol (PubChem CID: 10364); Catechol (PubChem CID: 289); Chaenomic acid A (PubChem CID: 102339344); Daucosterol (PubChem CID: 5742590); Genistein (PubChem CID: 5280961); Isohapontigenin (PubChem CID: 5318650); Kaempferol (PubChem CID: 5280863); Luteolin (PubChem CID: 5280445); Methyl linoleate (PubChem CID: 5284421); Molecular simulation; Phenols; Piceatannol (PubChem CID: 667639); Pickled radish; Quercetin (PubChem CID: 5280343); Resveratrol (PubChem CID: 445154); Xanthine oxidase; p-coumaric acid (PubChem CID: 637542); α-Linolenic (PubChem CID: 5280934); β-Sitosterol (PubChem CID: 222284).