Anti-inflammatory Mechanism of 15,16-Epoxy-3伪-hydroxylabda-8,13(16),14-trien-7-one via Inhibition of LPS-Induced Multicellular Signaling Pathways

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• 作者：Salman Khan ; Omer Shehzad ; Hong-Guang Jin ; Eun-Rhan Woo ; Sam Sik Kang ; Sa Wang Baek ; Jinwoong Kim ; Yeong Shik Kim
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：January 27, 2012
• 年：2012
• 卷：75
• 期：1
• 页码：67-71
• 全文大小：292K
• 年卷期：v.75,no.1(January 27, 2012)
• ISSN：1520-6025

文摘

Phytochemical investigation of Leonurus japonicus has led to the isolation of a labdane diterpene derivative, 15,16-epoxy-3伪-hydroxylabda-8,13(16),14-trien-7-one (1), which was tested for its in vitro anti-inflammatory effects. The results demonstrated that 1 exhibits an inhibitory effect on LPS-stimulated RAW 264.7 macrophages. The anti-inflammatory action shown by 1 suppressed LPS-induced NF-魏B activation, resulting in the down-regulation of iNOS and COX-2 protein expression, attributable to the inhibitory action of LPS-induced NO and PGE₂ production. Compound 1 inhibited LPS-induced phosphorylation and the degradation of inhibitory kappa B (I魏B伪) and decreased the nuclear translocation of p50 and p65. In addition, 1 exhibited an inhibitory effect on LPS-induced NF-魏B-DNA and AP-1-DNA binding activity, using an electrophoretic mobility shift assay with NF-魏B- and AP-1-specific ³²P-labeled probes. The LPS-induced mitogen-activated protein kinases (p-JNK, p-p38, and p-ERK) and p-Akt were inhibited after 30 and 10 min of LPS stimulation, respectively. In addition, TNF-伪 production was suppressed by 1.