Inhibition of Xanthine Oxidase by 1-O-Methyl Chrysophanol, A Hydroxyanthraquinone Isolated from Amycolatopsis Thermoflava ICTA 103.

UNLABELLED: The aim of this study was to isolate a potent xanthine oxidase (XO) inhibitor from actinobacteria and to investigate its inhibitory mechanism through in vitro and in vivo models. Culture filtrates from various actinobacterial strains i.e. Amycolatopsis thermoflava ICTA103, Streptomyces luteireticuli ICTA16, Streptomyces kurssanovii ICTA165, and Amycolatopsis lurida ICTA194 were screened for XO inhibitory activity. Among these, A. thermoflava ICTA103 exhibited the strongest inhibition, and 1-O-methyl chrysophanol (OMC) was identified as the lead compound. The cytotoxicity, and XO inhibitory potential of OMC were evaluated using in silico modeling, biochemical assays, in vitro cell lines, and in vivo animal models. Lineweaver-Burk plot analysis determined the IC50 and Ki values of OMC to be 24.8 ± 0.072 μM and 2.218 ± 0.3068 μM, respectively. Molecular docking studies confirmed that OMC effectively binds to the active site of XO. Cell line experiments indicated that OMC is non-toxic and significantly downregulates pro-inflammatory cytokines (IL-8, TNF-α) in a gouty arthritis model. Similarly, in vivo studies in mice showed no toxicity up to a dose of 2000 mg/kg body weight and demonstrated a significant reduction in serum uric acid levels in a hyperuricemic mouse model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-025-01534-4.