The anti-inflammatory effect of tussilagone, from Tussilago farfara, is mediated by the induction of heme oxygenase-1 in murine macrophages.
Tussilagone (TSL), isolated from the flower of buds of Tussilago farfara (Compositae), is a sesquiterpenoid that is known to exert a variety of pharmacological activities. In the present study, we demonstrated that TSL exerts anti-inflammatory activities in murine macrophages by inducing heme oxygenase-1 (HO-1) expression. Treatment of RAW264.7 cells with TSL-induced HO-1 protein expression in a dose- and time-dependent manner without the induction of HO-1 mRNA expression. TSL-mediated HO-1 protein induction was not inhibited by treatment with actinomycin D, a transcriptional inhibitor, but by cycloheximide, a translational inhibitor. Moreover, mitogen-activated protein kinases (MAPKs) inhibitors such as SB203580, SP600125, and U0126 did not block TSL-mediated HO-1 protein expression, suggesting that the TSL-mediated HO induction may be regulated at the translational level. Consistent with the notion that HO-1 has anti-inflammatory properties, TSL inhibited the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and prostaglandin E2 (PGE2) as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and murine peritoneal macrophages. Inhibition of HO-1 activity by treatment with zinc protoporphyrin IX (ZnPP), a specific HO-1 inhibitor, abrogated the inhibitory effects of TSL on the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. Taken together, TSL may be an effective HO-1 inducer that has anti-inflammatory effects, and a valuable compound for modulating inflammatory conditions.
Hwangbo
Cheol
C
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Lee
Hyun Sun
HS
Park
Juhee
J
Choe
Jongseon
J
Lee
Jeong-Hyung
JH
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000494:pharmacology*; D031207:Tussilago
D019384:Nucleic Acid Synthesis Inhibitors; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011524:Protoporphyrins; D012333:RNA, Messenger; D012717:Sesquiterpenes; C017803:zinc protoporphyrin; D003609:Dactinomycin; C054337:tussilagone; D003513:Cycloheximide; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases