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Int Immunopharmacol. 2011 Sep;11(9):1150-9. doi: 10.1016/j.intimp.2011.03.012. Epub 2011 Apr 5.

Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin.

Author information

1
Department of Biochemistry, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. tago-mg@pha.keio.ac.jp

Abstract

Flavonoids are widely distributed in many fruits and plants, and it has been shown that most flavonoids have anti-inflammatory activity; however, the mechanisms of how the flavonoids exhibit their anti-inflammatory activity have not been clarified. We therefore focus on flavonoids Apigenin, Luteolin and Fisetin because of their related structure. We found that these compounds significantly inhibited TNFα-induced NF-κB transcriptional activation; however, they had no effect on the degradation of IκB proteins and the nuclear translocation and DNA binding activity of NF-κB p65. Interestingly, the suppression of NF-κB activation by these flavonoids is due to inhibition of the transcriptional activation of NF-κB, since the compounds markedly inhibited the transcriptional activity of GAL4-NF-κB p65 fusion protein. In addition, while Apigenin and Luteolin slightly inhibited TNFα-induced JNK activation, they had no effect on TNFα-induced activation of ERK and p38. Unexpectedly, Fisetin enhanced and sustained activation of ERK and JNK but not p38 in response to TNFα. Strikingly, TNFα-induced expression of CCL2/MCP-1 and CXCL1/KC was significantly inhibited by Apigenin and Luteolin but not Fisetin. Furthermore, the administration of Apigenin and Luteolin markedly inhibited acute carrageenan-induced paw edema in mice; however, Fisetin failed to have an effect. These observations strongly suggest that the slight structural difference in flavonoids may cause a defective effect of Fisetin on these inflammatory responses, and this may be due to the differences in their direction of the effect on the activation pathways of MAP kinases.

PMID:
21443976
DOI:
10.1016/j.intimp.2011.03.012
[Indexed for MEDLINE]

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