4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor gamma agonist alleviates the symptoms of DSS-induced colitis.
(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma) and antidiabetic agent as has been previously reported. As PPARgamma agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.
Yamamoto
Keiko
K
Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Ninomiya
Yuichi
Y
Iseki
Mioko
M
Nakachi
Yutaka
Y
Kanesaki-Yatsuka
Yukiko
Y
Yamanoue
Yu
Y
Itoh
Toshimasa
T
Nishii
Yasuho
Y
Petrovsky
Nikolai
N
Okazaki
Yasushi
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index
C526920:4-hydroxy-5,7,10,13,16,19-docosahexaenoic acid; D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D008070:Lipopolysaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; D009569:Nitric Oxide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse