Cudratricusxanthone A from Cudrania tricuspidata suppresses pro-inflammatory mediators through expression of anti-inflammatory heme oxygenase-1 in RAW264.7 macrophages.
Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata Bureau (Moraceae) has an isoprenylated xanthone skeleton that is known to exert a variety of biological activities. In the present study, we demonstrated that CTXA inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase (iNOS) expression, and thereby reduced COX-2-derived prostaglandin E2 (PGE(2)) and iNOS-derived NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, CTXA suppressed tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production. Moreover, CTXA inhibited the induced phosphorylation and degradation of IkappaB-alpha as well as the LPS-induced increase in p65 in the nuclear fraction of macrophages. CTXA also induced heme oxygenase-1 (HO-1) expression and increased heme oxygenase (HO) activity in RAW264.7 macrophages. We also demonstrated that the effects of CTXA on LPS-induced PGE(2), NO, TNF-alpha, and IL-1beta production were partially reversed by the HO-1 inhibitor tin protoporphyrin, suggesting that CTXA-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects of the drug. Thus CTXA was shown to be an effective HO-1 inducer, capable of inhibiting macrophage-derived pro-inflammatory mediators.
Jeong
Gil-Saeng
GS
Institute for Radiological Imaging Science, Wonkwang University, Iksan 570-749, Republic of Korea.
Lee
Dong-Sung
DS
Kim
Youn-Chul
YC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000276:immunology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D029586:Moraceae / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C533013:cudratricusxanthone A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D015232:Dinoprostone