Resveratrol as a bioenhancer to improve anti-inflammatory activities of apigenin

Apigenin is found in high amounts in several herbs including parsley, thyme, and peppermint. It has been reported as an important dietary flavonoid with strong anti-inflammatory activities [1]. It is extensively metabolized and mainly eliminated in humans by first-pass metabolism via glucuronidation and sulfation [2,3]. 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%). These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

Acknowledgements: This study was supported by research program of Korea food research institute.

Keywords: anti-inflammation, bioenhancer, hepatic metabolites of apigenin, UDP-glucuronosyltransferase (UGT).

References:

[1] Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff AI. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol 2007; 179: 7121 – 7127

[2] Nielsen SE, Dragsted LO. Column-switching high-performance liquid chromatographic assay for determination of apigenin and acacetin in human urine with ultraviolet absorbance detection. J Chromatogr B Biomed Sci Appl 1998; 713: 379 – 386

[3] Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther 2002; 96: 67 – 202

No conflict of interest has been declared by the author(s).