Hesperidin inhibits expression of hypoxia inducible factor-1 alpha and inflammatory cytokine production from mast cells.
The citrus unshiu peel has been used traditionally as a medicine to improve bronchial and asthmatic conditions or cardiac and blood circulation in Korea, China, and Japan. Here, we report the effects of citrus unshiu peel water extract (CPWE) on the phorbol myristate acetate (PMA)+calcium ionophore A23187-induced hypoxia-inducible factor-1alpha (HIF-1alpha) activation and inflammatory cytokine production from the human mast cell line, HMC-1 cells. We compared CPWE with hesperidin, a common constituent of citrus unshiu. CPWE and hesperidin inhibited the PMA+A23187-induced HIF-1alpha expression and the subsequent production of vascular endothelial growth factor (VEGF). In addition, CPWE suppressed PMA+A23187-induced phosphorylation of the extracellular signal-regulated kinase (ERK). We also show that the increased cytokines interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha level was significantly inhibited by treatment of CPWE or hesperidin. In the present study, we report that CPWE and hesperidin are inhibitors of HIF-1alpha and cytokines on the mast cell-mediated inflammatory responses.
Choi
In-Young
IY
College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
Kim
Su-Jin
SJ
Jeong
Hyun-Ja
HJ
Park
Seong-Heak
SH
Song
Yong-Sun
YS
Lee
Ji-Hyun
JH
Kang
Tae-Hee
TH
Park
Jin-Han
JH
Hwang
Gab-Soo
GS
Lee
Eon-Jeong
EJ
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
Um
Jae-Young
JY
D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002957:Citrus / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006367:HeLa Cells; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D007476:Ionophores; D042461:Vascular Endothelial Growth Factor A; D000001:Calcimycin; D006569:Hesperidin; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate