Anti-inflammatory action of methanol extract of Carthamus tinctorius involves in heme oxygenase-1 induction.
BACKGROUND
The methanol extracts of Carthamus tinctorius (MEC) have long been used in traditional medicine as anti-inflammatory agent, however, the molecular mechanism by which MEC shows anti-inflammatory action is not investigated.


OBJECTIVE
Induction of heme oxygenase-1 (HO-1) by many medicinal herbs has been reported excellent anti-inflammatory action. Thus, the aim of the study is to explore whether anti-inflammatory action of MEC is related with HO-1 induction in RAW 264.7 cells.


METHODS
The present study was designed to investigate as to MEC induces HO-1 expression so that it reduces inflammation by suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in cells activated with lipopolysaccharide (LPS).


RESULTS
Expression of HO-1 protein by MEC in macrophages was increased in a concentration- and time-dependent manner. Treatment with MEC significantly inhibited upregulation of both iNOS and COX-2 in LPS-activated macrophages and consequently reduced production of NO and PGE(2), respectively. The reduced expression of iNOS and COX-2 by MEC was reversed by siHO-1 RNA transfection. In addition, NF-E2-related factor (Nrf2) was translocated from cytosol to nucleus by MEC. The binding of NF-κB as well as NF-κB luciferase activity was also significantly diminished by MEC. Finally, tumor necrosis factor (TNF)-α-mediated VCAM-1 expression in endothelial cell was significantly inhibited by MEC.


CONCLUSIONS
The present results show that MEC induces HO-1 expression via Nrf2 translocation and inhibits NF-κB activity, which may be responsible for anti-inflammatory action. Therefore, we propose that anti-inflammatory action of MEC involves at least HO-1 induction.
Jun
Min Soo
MS
Department of Pharmacology, School of Medicine, and Institute of Health Sciences, Gyeongsang National University, 92 Chilam-dong, Jinju 660-751, Republic of Korea.
Ha
Yu Mi
YM
Kim
Hee Sook
HS
Jang
Hwa Jin
HJ
Kim
Young Min
YM
Lee
Young Soo
YS
Kim
Hye Jung
HJ
Seo
Han Geuk
HG
Lee
Jae Heun
JH
Lee
Seung Ho
SH
Chang
Ki Churl
KC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D031187:Carthamus tinctorius / Q000737:chemistry; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004790:Enzyme Induction / Q000187:drug effects; D020834:Ethnopharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D055670:Medicine, Korean Traditional; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000432:Methanol; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics; D056910:Republic of Korea; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000432:Methanol