Exploring Asphodelus microcarpus as a source of xanthine oxidase inhibitors: Insights from in silico and in vitro studies

• Published in: Chemico-biological interactions Vol. 397; p. 111087
• Main Authors: Di Petrillo, Amalia, Siguri, Chiara, Delogu, Giovanna L., Fais, Antonella, Era, Benedetta, Floris, Sonia, Pintus, Francesca, Kumar, Amit, Fantini, Massimo Claudio, Olla, Stefania
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.07.2024
• Subjects: Allopurinol - chemistry; Allopurinol - pharmacology; Binding Sites; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Flowers - chemistry; Glucosides - chemistry; Glucosides - pharmacology; Humans; Luteolin - chemistry; Luteolin - pharmacology; Luteolin derivates; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Plant Extracts - chemistry; Plant Extracts - pharmacology; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism; Molecular dynamics; Xanthine oxidase; Luteolin derivates; Molecular docking
• ISSN: 0009-2797; 1872-7786; 1872-7786
• DOI: 10.1016/j.cbi.2024.111087

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC50 value of 4.8 μg/mL compared to 11.5 μg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management. •A. microcarpus flower extract inhibits xanthine oxidase (XO) via mixed-type inhibition.•Luteolin-7-O-glucoside stably binds XO in AutoDock and 250ns molecular dynamics.•Luteolin 7-O-glucoside demonstrates in vitro XO inhibition (IC50 4.8 μg/mL).