Marine-Derived Secondary Metabolite, Griseusrazin A, Suppresses Inflammation through Heme Oxygenase-1 Induction in Activated RAW264.7 Macrophages

详细信息    查看全文

• 作者：Dong-Sung Lee ; Chi-Su Yoon ; Yong-Taek Jung ; Jung-Hoon Yoon ; Youn-Chul Kim ; Hyuncheol Oh
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：April 22, 2016
• 年：2016
• 卷：79
• 期：4
• 页码：1105-1111
• 全文大小：402K
• 年卷期：0
• ISSN：1520-6025

文摘

A new secondary metabolite, named griseusrazin A (1), was isolated from the marine-derived bacterium Streptomyces griseus subsp. griseus. The structure of the compound was determined by analysis of spectroscopic data including MS, COSY, HSQC, HMBC, and ¹⁵N-HMBC data. Griseusrazin A (1) inhibited the production of inflammatory mediators, such as prostaglandin E₂ and nitric oxide, which was mediated through the suppression of the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The production of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, in the LPS-stimulated cells was also effectively blocked by griseusrazin A (1). Furthermore, this anti-inflammatory activity of 1 was linked to its inhibitory effects against the nuclear translocation of NF-κB p50 and p65, as wells as NF-κB binding activity. In the further study to elucidate the anti-inflammatory mechanism, 1 was shown to induce heme oxygenase-1 (HO-1) expression through the enhancement of nuclear translocation of nuclear factor E2-related factor 2. Furthermore, the anti-inflammatory activity of 1 in the LPS-stimulated cells was partially reversed by an HO inhibitor, tin protoporphyrin. These results indicate that the anti-inflammatory effect of 1 is associated with Nrf2-mediated HO-1 expression.