Abstract
Xanthine oxidase is a frontier enzyme to produce oxidants, which leads to inflammation in the blood. Prenylated isoflavones from Flemingia philippinensis were found to display potent inhibition against xanthine oxidase (XO). All isolates (1–9) inhibited XO enzyme with IC50 ranging 7.8~36.4 μM. The most active isoflavones (2–5, IC50 = 7.8~14.8 μM) have the structural feature of a catechol motif in B-ring. Inhibitory behaviors were disclosed as a mixed type I mode of inhibition with KI < KIS. Binding affinities to XO enzyme were evaluated. Fluorescence quenching effects agreed with inhibitory potencies (IC50s). The compounds (2–5) also showed potent anti-LDL oxidation effects in the thiobarbituric acid-reactive substances (TBARS) assay, the lag time of conjugated diene formation, relative electrophoretic mobility (REM), and fragmentation of apoB-100 on copper-mediated LDL oxidation. The compound 4 protected LDL oxidation with 0.7 μM in TBARS assay, which was 40-fold more active than genistein (IC50 = 30.4 μM).
Highlights
Reactive oxygen species (ROS) have received important consideration due to their adjusted role in signaling during inflammation [1,2]
We explored effective antioxidant substances blocking xanthine oxidase (XO) enzymes as well as low-density lipoprotein (LDL) oxidation
These isoflavones have biological functions as enzyme inhibitors, and antitumor activities relating to ROS and angiogenesis [29,30]
Summary
Reactive oxygen species (ROS) have received important consideration due to their adjusted role in signaling during inflammation [1,2]. These oxidants produced commonly by NAD(P)H oxidase, nitric oxide (NO) synthase and xanthine oxidoreductase (XOR) as well as environmental factors such as stress, smoking, etc. Controlling of XO excessive expression by its inhibitors—allopurinol and febuxostat—as the most widely prescribed commercial drugs, is important for human health, in particular, in regulation of vascular function [10] They are often limited due to their inverse side effects, so the discoveries of new XO inhibitors are increasing
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