Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 58, Issue 2, Pages 860-867Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf9033333
Keywords
Isoegomaketone; nitric oxide; lipopolysaccharide; STAT-1; heme oxygenase-1
Funding
- Agricultural R&D Promotion Center, Korea Rural Economic institute
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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-kappa B 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.
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