RESUMO
Xanthine oxidase (XO) plays a critical role in the progression of gout. We showed in a previous study that Sanghuangporus vaninii (S. vaninii), a perennial, medicinal, and edible fungus traditionally used to treat various symptoms, contains XO inhibitors. In the current study, we isolated an active component of S. vaninii using high performance countercurrent chromatography and identified it as davallialactone using mass spectrometry with 97.726 % purity. A microplate reader showed that davallialactone had mixed inhibition of XO activity with a half-inhibitory concentration value of 90.07 ± 2.12 µM. In addition, the collision between davallialactone and XO led to fluorescence quenching and conformational changes in XO, which were mainly driven by hydrophobicity and hydrogen bonding. Molecular simulations further showed that davallialactone was located at the center of the molybdopterin (Mo-Pt) of XO and interacted with amino acid residues Phe798, Arg912, Met1038, Ala1078, Ala1079, Gln1194, and Gly1260, suggesting that entering the enzyme-catalyzed reaction was unfavorable for the substrate. We also observed face-to-face π-π interactions between the aryl ring of davallialactone and Phe914. Cell biology experiments indicated that davallialactone reduced the expression of the inflammatory factors, tumor necrosis factor alpha and interleukin-1 beta (P < 0.05), can effectively alleviate cellular oxidative stress. This study showed that davallialactone significantly inhibits XO and has the potential to be developed into a novel medicine to prevent hyperuricemia and treat gout.
Assuntos
Basidiomycota , Gota , Xantina Oxidase , Humanos , Inibidores Enzimáticos/química , Gota/tratamento farmacológico , Simulação de Acoplamento Molecular , Xantina Oxidase/efeitos dos fármacos , Basidiomycota/químicaRESUMO
BACKGROUND: Drug-eluting stent technology has rapidly developed in recent years. In particular, stents are used in percutaneous coronary intervention (PCI), which has become a vital method in clinic treatment. Although various methods are currently used to prepare drug-eluting stents, these methods are associated with respective limitations. OBJECTIVE: To design equipment for preparing drug-eluting stents with single-sided coating and to precisely accomplish the drug-coating process for a single side. METHODS: This coating equipment prepared stents in three stages: the precise displacement and translational motion and rotational motion of the operating platform; the recognition and positioning of the stent strut; and the utilisation of a pL-scale inkjet system. In order to control and synchronise the work of each subsystem, a central processing unit was installed. RESULTS: Through the analysis and solutions of various problems occurring in the experiment, the spraying equipment was improved, and its functions were perfected. Thus, the successful operation of the spraying equipment was realised. CONCLUSIONS: The design of the equipment introduced in this article meets the requirements for preparing drug-eluting stents.