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Nutrients 2015, 7(11), 9650-9661; doi:10.3390/nu7115485

Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin

Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Institute, 1201-62, Anyangpangyoro, Seongnam, Gyeonggi 463-746, Korea
These authors contributed equally to this work.
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Received: 18 August 2015 / Accepted: 9 November 2015 / Published: 19 November 2015
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Abstract

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin’s anti-inflammatory activities in the body. View Full-Text
Keywords: anti-inflammation; bioenhancer; hepatic metabolites of apigenin; UDP-glucuronosyltransferase (UGT) anti-inflammation; bioenhancer; hepatic metabolites of apigenin; UDP-glucuronosyltransferase (UGT)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lee, J.-A.; Ha, S.K.; Cho, E.; Choi, I. Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin. Nutrients 2015, 7, 9650-9661.

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