Stereochemical Determination of Fistularins Isolated from the Marine Sponge Ecionemia acervus and Their Regulatory Effect on Intestinal Inflammation |
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Authors: | Yeong Kwang Ji Seon Min Lee Na-Hyun Kim Nguyen Van Tu Yun Na Kim Jeong Doo Heo Eun Ju Jeong Jung-Rae Rho |
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Affiliation: | 1.Department of Oceanography, Kunsan National University, Gunsan 54150, Korea;2.Gyeongnam Department of Environment & Toxicology, Korea Institute of Toxicology, 17 Jegok-gil, Munsan-eup 52834, Korea; (S.M.L.); (N.-H.K.); (J.D.H.);3.Institute of Tropical Biology, 85 Tran Quoc Toan Street District 3, Ho Chi Minh 700000, Vietnam;4.Department of Plant & Biomaterials Science, Gyeonsang National University, Jinju 52725, Korea; |
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Abstract: | By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1–6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher’s method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease. |
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Keywords: | fistularin, bromotyrosine alkaloid, Ecionmeia acervus, inflammatory bowel disease, co-culture, Mosher’ s ester |
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