Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol)

Free Radical Biology & Medicine
Klaus Uhlenhut, Petra Högger

Abstract

Many natural products exhibit anti-inflammatory activity by suppressing excessive nitric oxide (NO) production by inducible NO synthase (iNOS). The maritime pine bark extract Pycnogenol has been formerly shown to decrease nitrite generation, taken as an index for NO, but so far it was not clear which constituent of the complex flavonoid mixture mediated this effect. The purpose of this study was to elucidate whether the in vivo generated Pycnogenol metabolite M1 (δ-(3,4-dihydroxyphenyl)-γ-valerolactone) displayed any activity in the context of induction of iNOS expression and excessive NO production. For the first time we show that M1 inhibited nitrite production (IC(50) 1.3 μg/ml, 95% CI 0.96-1.70) and iNOS expression (IC(50) 3.8 μg/ml, 95% CI 0.99-14.35) in a concentration-dependent fashion. This exemplifies bioactivation by metabolism because the M1 precursor molecule catechin is only weakly active. However, these effects required application of M1 in the low-micromolar range, which was not consistent with concentrations previously detected in human plasma samples after ingestion of maritime pine bark extract. Thus, we investigated a possible accumulation of M1 in cells and indeed observed high-capacity binding of this flavo...Continue Reading

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Citations

May 31, 2015·Journal of Pharmaceutical and Biomedical Analysis·Melanie MülekPetra Högger
Feb 27, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Maria Angeles MartinSonia Ramos
Jan 22, 2015·Journal of Agricultural and Food Chemistry·Jianbo Xiao, Petra Högger
Apr 27, 2016·Journal of Agricultural and Food Chemistry·Yoon Hee KimHirofumi Tachibana
Aug 3, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhenzhen Xue, Bin Yang
May 23, 2018·Critical Reviews in Food Science and Nutrition·Arpita Banerjee, Pubali Dhar
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Sep 25, 2019·Nutrients·Estefanía Márquez CamposMarie-Christine Simon
Feb 25, 2020·Critical Reviews in Food Science and Nutrition·Zhihao QuSheng Zhang
Mar 29, 2018·Nutrients·Annelies A J VerlaetHuub F J Savelkoul
Jan 27, 2019·Nutrients·Annelies VerlaetMalgorzata Teodorowicz
Oct 13, 2020·International Journal of Antimicrobial Agents·Franziska Weichmann, Peter Rohdewald
Feb 11, 2021·International Journal of Molecular Sciences·Rami S Najjar, Rafaela G Feresin

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