Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol

Abstract

In this study, the mechanism of the xanthine oxidase (XO) inhibitory activity of pyrogallol, the main inhibitor found in roasted coffee, was investigated. Pyrogallol was unstable and readily converted to purpurogallin in a pH 7.4 solution, a physiological model of human body fluids. The XO inhibitory activity of the produced purpurogallin was higher than that of pyrogallol, as evidenced by comparing their IC values (0.2µmolL for purpurogallin, 1.6µmolL for pyrogallol). The XO activity of pyrogallol was enhanced by pre-incubation in pH 7.4 solution. Although the initial XO inhibitory activity of 4-methylpyrogallol was weak (IC 33.3µmolL), its XO inhibitory activity was also enhanced by pre-incubation in the pH 7.4 solution. In contrast, 5-methylpyrogallol, which could not be transformed into corresponding purpurogallin derivatives, did not show XO inhibitory activity before or after incubation in pH 7.4 solution. Molecular docking simulations clarified that purpurogallins have stronger affinities for XO than corresponding pyrogallols. These results revealed that the potent XO inhibitory activity seemingly observed in pyrogallol is actually derived from its chemical conversion, under alkaline conditions, into purpurogallin.

Optimization of total phenolic contents, antioxidant, andin-vitroxanthine oxidase inhibitory activity of sunflower head

“…), enter the Mo center of XOD, thwart electron transfer, and alternate the structure of XOD which results in preventing UA synthesis (Honda, Fukuyama, Nishiwaki, Masuda, & Masuda, 2017;Mehmood et al, 2017;Wang, Zhang, Pan, & Gong, 2015;Yan, Zhang, Hu, & Ma, 2013;Zhang et al, 2016). Similar, the mechanism of XOD inhibition by dietary polyphenols was proposed by numerous researchers (Dong et al, 2016;Honda et al, 2017;Yan et al, 2013).…”

Inhibitory Effect of Purpurogallin on Osteoclast Differentiation in Vitro through the Downregulation of c-Fos and NFATc1

“…Purpurogallin occurs naturally in oak trees infested with hymenopterous insects, and can also be synthesized by the chemical oxidation of pyrogallol using peroxidase [ 27 ]. Under physiological conditions (pH 7.4), pyrogallol is unstable and rapidly converts to purpurogallin [ 13 ]. Honda et al reported that purpurogallin exhibits higher affinity for xanthine oxidase (XO) than pyrogallol and plays an important role in enhancing the XO inhibitory effect of pyrogallol [ 13 ].…”

“…[ 10 , 11 ]. It has been reported to inhibit the activity of enzymes, including glutathione S-transferase, xanthine oxidase, and catechol O -methyltransferase [ 12 , 13 , 14 ]. In addition, purpurogallin has been shown to have peroxyl radical scavenging activity [ 15 ].…”

Natural compounds with xanthine oxidase inhibitory activity: A review

“…In-vitro XOD inhibition via flavonoids has been extensively studied by numerous researchers (Figures 4-6 and Table 1). Multiple spectroscopic (circular dichroism, fluorescence titrations), kinetic analysis, Fourier-transform infrared spectroscopy, thermodynamic characteristics, crystallographic, and computation simulation techniques were applied for unraveling the XOD inhibitory mechanism by flavonoids (Cao, Pauff, & Hille, 2014;Dong et al, 2016;Gawlik-Dziki, Dziki, Świeca, & Nowak, 2017;Honda, Fukuyama, Nishiwaki, Masuda, & Masuda, 2017;Lespade & Bercion, 2009;Lin, Zhang, Liao, Pan, & Gong, 2015;Masuoka, Isobe, & Kubo, 2006;Pauff & Hille, 2009;Van Hoorn et al, 2002;Wang, Zhang, Pan, & Gong, 2015;Yan et al, 2013;Zhang, Wang, Zhang, & Gong, 2018;Zhang, Zhang, Pan, & Gong, 2016).…”