Xanthine Oxidase Inhibition and Anti-LDL Oxidation by Prenylated Isoflavones from Flemingia philippinensis Root

Abstract

<jats:p>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 &lt; 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).</jats:p>

Changes in secondary metabolites in soybean (Glycine max L.) roots by salicylic acid treatment and their anti-LDL oxidation effects

“…The relative electrophoretic mobility (REM) of native LDL and oxidized LDL induced by Cu 2+ was measured according to procedures in previous reports ( Kim et al, 2020a ). Before electrophoresis, the reaction mixtures including the 10 μM CuSO 4 and the compounds, samples of soybean root extract, or probucol as a positive control at various concentrations were added to the LDL solution (500 μg/ml), then incubated at 37°C for 16 h in the dark.…”

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

“…Their antioxidant activity was less than ascorbic acid. Additionally, the kinetic oxy-2′,5′-di(3-methylbut-2-enyl)isoflavone, flemiphilippinin A (IC 50 = 7.8-14.8 μM) were found to be most potent with mixed type I inhibition (K I < K IS ) against XO and also displayed anti-LDL (low-density lipoprotein) oxidation effects (Kim et al, 2020). Kumar et al (2019) isolated two new compounds, lasdiplactone and lasdiploic acid, and a known compound 54 ((3S,4R,5R)-4-(hydroxymethyl)-3,5dimethyldihydrofuran-2(3H)-one) from the chloroform extract of endophytic fungus Lasiodiplodia pseudotheobromae as XO inhibitors.…”

“…Additionally, the kinetic parameters demonstrated the competitive mode of inhibition by piceatannol and the uncompetitive mode of inhibition by the remaining three compounds (Tang et al, 2019). Kim et al (2020) isolated prenylated isoflavones from Flemingia philippinensis to discover XO inhibitors. All compounds exhibited inhibitory potency against XO with IC 50 ranging from 7.8 to 36.4 μM.…”

“…All compounds exhibited inhibitory potency against XO with IC 50 ranging from 7.8 to 36.4 μM. Among them, isoflavones auriculasin, 6,8‐diprenylorobol, 5,7,3′,4′‐tetrahydroxy‐2′,5′‐di(3‐methylbut‐2‐enyl)isoflavone, flemiphilippinin A (IC 50 = 7.8–14.8 μM) were found to be most potent with mixed type I inhibition (K I < K IS ) against XO and also displayed anti‐LDL (low‐density lipoprotein) oxidation effects (Kim et al, 2020).…”

“…competitive mode of inhibition by piceatannol and the uncompetitive mode of inhibition by the remaining three compounds(Tang et al, 2019) Kim et al (2020). isolated prenylated isoflavones from Flemingia philippinensis to discover XO inhibitors.…”