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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
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2015, 7(11), 9650-9661;
Received: 18 August 2015 / Accepted: 9 November 2015 / Published: 19 November 2015
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)
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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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