Elucidation of 7,8-dihydroxy flavone in complexing with the oxidative stress-inducing enzymes, its impact on radical quenching and DNA damage: anin silicoandin vitroapproach

AbstractAbstractOxidative stress (OS) has been attributed to the progression of various disorders, including cancer, diabetes, and cardiovascular diseases. Several antioxidant compounds and free radical quenchers have been shown to mitigate oxidative stress. However, large-scale randomized controlled trials of such compounds on chronic disease aversion have yielded paradoxical and disappointing results due to the constrained cognizance of their oxidative mechanisms and therapeutic targets. The current study sought to identify the potential therapeutic targets of 7,8-Dihydroxyflavone (7,8-DHF) by analyzing its interactions with the enzymes implicated in oxidative stress and also to explore its radicle quenching potential and prophylactic impact on the H2O2-induced DNA damage. Through the in silco approach, we investigated the antioxidant potential of 7,8-DHF by evaluating its interactions with the human oxidative stress-inducing enzymes such as myeloperoxidase (MPO), NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO) and a comparative analysis of those interactions with known antioxidants (Ascorbic acid, Melatonin, Tocopherol) used as controls. The best-scoring complex was adopted for the simulation analysis in investigating protein-ligand conformational dynamics. The in vitro radicle quenching potential was evaluated by performing a spectrum of antioxidant assays, and radical quenching was observed in a dose-dependent fashion with IC50 values of < 60 µM/mL. Further, we probed its anti-hemolytic potential and prophylactic impact in avian erythrocytes subjected to H2O2-induced hemolysis and DNA damage by implementing hemolysis and comet assays. The protective effect was more pronounced at higher concentrations of the drug.Communicated by Ramaswamy H. SarmaKeywords: Oxidative stressmolecular dockingflavonoidsprotective effect7,8 dihydroxyflavonehomology modeling AcknowledgmentsThe author IHM and SG acknowledges Pondicherry University and UGC for providing UGC Non-NET fellowship. IHM also acknowledges the Indian Council of medical research for providing ICMR-SRF fellowship (45/17/2022-/BIO/BMS). The author VS acknowledges DST in the form of DSTKIRAN/Mobility/Sujatha/2019.Disclosure statementThe authors report there are no competing interests to declare.Authors’ contributionsIHM: Conception of the study, literature search, drafting, and execution of experiments; ASA: Data interpretation, conducted experiments; SG: Result analysis; AKM: In silico research; MSK: Resources, supervision; VS: Investigation, Data curation, Formal analysis; RT: Data curation, formal analysis CT: Fundamental concepts of the study, supervision, proofreading, and manuscript editing.Data availability statementThe data that support the findings of this study are available within the article and its supplementary materials.Additional informationFundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.