Abstract
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-1β and Tumor Necrosis Factor alpha (TNF-α). 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.
Highlights
Inflammatory bowel disease (IBD) that clinically includes Crohn’s disease (CD) and ulcerative colitis (UC) is known to result from inappropriate and chronic inflammatory responses to commensal flora in a genetically susceptible host [1]
It has been demonstrated that immune cells isolated from IBD patients display markedly increased level Itof has inflammatory mediators compared to those normal tissues
Increased levels been demonstrated that immune cellsfrom isolated from patients display markedly of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 are observed in IBD
Summary
Inflammatory bowel disease (IBD) that clinically includes Crohn’s disease (CD) and ulcerative colitis (UC) is known to result from inappropriate and chronic inflammatory responses to commensal flora in a genetically susceptible host [1]. In patients with Crohn’s disease, one of the clinical features is discontinuous segments of inflammation that are found in any part of the gastrointestinal tract. Mar. Drugs 2019, 17, 634; doi:10.3390/md17110634 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2019, 17, 634 of CD include thickened submucosa, transmural inflammation, non-caseating granulomas, strictures and fistulas that lead to bowel obstruction [1,2]. UC is characterized by the limited inflammatory region which usually begins in the rectum and spreads in a continuous fashion
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