Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine |
| |
Authors: | Yun Na Kim Yeong Kwang Ji Na-Hyun Kim Nguyen Van Tu Jung-Rae Rho Eun Ju Jeong |
| |
Institution: | 1.Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea;2.Department of Oceanography, Kunsan National University, Gunsan 54150, Korea;3.Gyeongnam Department of Environment & Toxicology, Korea Institute of Toxicology, 17 Jegok-gil, Munsan-eup, Jinju-si 52834, Korea;4.Institute of Tropical Biology, 85 Tran Quoc Toan Street District 3, Ho Chi Minh 700000, Vietnam; |
| |
Abstract: | Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1–8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease. |
| |
Keywords: | isoquinolinequinone Haliclona sp inflammation intestine inflammatory bowel disease co-culture |
|
|