Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-beta-STAT-1 pathway.
Isoegomaketone (IK) is an essential oil component of Perilla frutescens (L.) Britt., and there have been no studies investigating its biological activities. We found that IK inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages, and moreover, when IK was injected into animals prior to LPS administration, NO serum levels decreased in a dose-dependent manner. These results indicate that IK possesses anti-inflammatory activity both in vitro and in vivo. IK suppressed the phosphorylation of STAT-1 and the production of IFN-beta. Treatment with IK also inhibited the activation of NF-kappaB and activator protein-1, but more IK was required for inhibition than for STAT-1 inhibition, indicating that downregulation of inducible nitric oxide synthase gene expression by IK is mainly attributed to the blockade of STAT-1 activation. Furthermore, IK also induced the expression of heme oxygenase-1 (HO-1) through the activation of nuclear factor E2-related factor 2. Treatment with SnPP, a selective inhibitor of HO-1, reversed the IK-induced suppression of STAT-1 phosphorylation and NO production. Taken together, IK isolated from P. frutescens inhibits NO production in LPS-treated RAW 264.7 macrophages through simultaneous induction of HO-1 and inhibition of the IFN-beta-STAT-1 pathway.
Jin
Chang Hyun
CH
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
Lee
Hyo Jung
HJ
Park
Yong Dae
YD
Choi
Dae Seong
DS
Kim
Dong Sub
DS
Kang
Si-Yong
SY
Seo
Kwon-Il
KI
Jeong
Il Yun
IY
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000276:immunology*; D016899:Interferon-beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000276:immunology*; D009822:Oils, Volatile / Q000008:administration & dosage / Q000494:pharmacology*; D031344:Perilla frutescens / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D008070:Lipopolysaccharides; D009822:Oils, Volatile; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; D009569:Nitric Oxide; D016899:Interferon-beta; D051547:Heme Oxygenase-1