Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus Phyllospongia, with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine

被引:15
作者
Lee, Seon Min [1 ]
Kim, Na-Hyun [1 ]
Lee, Sangbum [2 ]
Kim, Yun Na [3 ]
Heo, Jeong Doo [1 ]
Jeong, Eun Ju [3 ]
Rho, Jung-Rae [2 ]
机构
[1] Korea Inst Toxicol, Gyeongnam Dept Environm & Toxicol, 17 Jegok Gil, Munsan Eup 52834, South Korea
[2] Kunsan Natl Univ, Dept Oceanog, Kunsan 54150, South Korea
[3] Gyeongnam Natl Univ Sci & Technol, Dept Agron & Med Plant Resources, Jinju 52725, South Korea
关键词
deacetylphylloketal; phyllohemiketal A; Phyllospongia; co-culture; intestine; inflammation; inflammatory bowel disease; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; BISHOMOSCALARANE SESTERTERPENES; ULCERATIVE-COLITIS; NITRIC-OXIDE; EXPRESSION; COX-2; CYTOKINES; 6-SHOGAOL; CELLS;
D O I
10.3390/md17110634
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1 beta and Tumor Necrosis Factor alpha (TNF-alpha). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.
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页数:17
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