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.
| Original language | English |
|---|---|
| Pages (from-to) | 1150-1159 |
| Number of pages | 10 |
| Journal | International Immunopharmacology |
| Volume | 11 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2011 Sep |
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Keywords
- Apigenin
- Fisetin
- Inflammation
- Luteolin
- TNFα
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Pharmacology
Cite this
Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin. / Tago, Megumi; Nakamura, Kei; Tago, Kenji; Mashino, Tadahiko; Kasahara, Tadashi.
In: International Immunopharmacology, Vol. 11, No. 9, 09.2011, p. 1150-1159.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin
AU - Tago, Megumi
AU - Nakamura, Kei
AU - Tago, Kenji
AU - Mashino, Tadahiko
AU - Kasahara, Tadashi
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Apigenin
KW - Fisetin
KW - Inflammation
KW - Luteolin
KW - TNFα
UR - http://www.scopus.com/inward/record.url?scp=80051896049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051896049&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2011.03.012
DO - 10.1016/j.intimp.2011.03.012
M3 - Article
VL - 11
SP - 1150
EP - 1159
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 9
ER -