title: The antioxidant effects of isorhamnetin contribute to inhibit COX-2 expression in response to inflammation: a potential role of HO-1.
abstract: Previously, we reported that isorhamnentin, a 3'-O-methylated metabolite of quercetin, reduced inducible nitric oxide synthase (iNOS) expression and NO production. The present study further investigated the underlying mechanism of anti-inflammatory and antioxidant effects of isorhamnentin. Administration of isorhamnetin decreased the number of cyclooxygenase-2 (COX-2) positive cells in rats with carrageenan-induced paw edema. Isorhamnetin also suppressed lipopolysaccharide (LPS)-induced expression of COX-2 in cells. It is well known that LPS-induced reactive oxygen species (ROS) production leads to COX-2 induction. Isorhamnetin decreased LPS-induced ROS production and apoptosis. In addition, the basal expression of heme oxygenase-1 (HO-1) was increased by isorhamnetin treatment in agreement with the increase in nuclear translocation of NF-E2-related factor-2 (Nrf2), an essential transcription factor for the regulation of HO-1 expression. Moreover, pretreatment of tin protoporphyrin IX (SnPP), a chemical inhibitor of HO-1, reversed the ability of isothamnetin to inhibit COX-2 expression. These results demonstrate that induction of HO-1 by isorhamnetin leads to a reduction in ROS production and its antioxidant property might contribute to the inhibition of COX-2 expression in response to inflammation.
authors: College of Pharmacy, Chosun University, Gwangju, 501-759, South Korea.
authors: Kyuhwa
authors: K
authors: Seo
authors: Ji Hye
authors: JH
authors: Yang
authors: Sang Chan
authors: SC
authors: Kim
authors: Sae Kwang
authors: SK
authors: Ku
authors: Sung Hwan
authors: SH
authors: Ki
authors: Sang Mi
authors: SM
authors: Shin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011524:Protoporphyrins / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C047368:3-methylquercetin; D009569:Nitric Oxide; D011794:Quercetin; C032628:tin protoporphyrin IX; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat