Penicillinolide A: a new anti-inflammatory metabolite from the marine fungus Penicillium sp. SF-5292.
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher's method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation.
Department of Pharmacy, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
Dong-Sung
DS
Lee
Wonmin
W
Ko
Tran Hong
TH
Quang
Kyoung-Su
KS
Kim
Jae Hak
JH
Sohn
Jae-Hyuk
JH
Jang
Jong Seog
JS
Ahn
Youn-Chul
YC
Kim
Hyuncheol
H
Oh
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010407:Penicillium / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D015232:Dinoprostone; D051547:Heme Oxygenase-1; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D007783:Lactones; D051267:NF-E2-Related Factor 2; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009569:Nitric Oxide; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C000606205:Nfkbia protein, mouse