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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Animals
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Anti-Inflammatory Agents / pharmacology
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Antioxidants / pharmacology*
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Apoptosis / drug effects
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Cell Line
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Cyclooxygenase 2 / biosynthesis*
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Edema / chemically induced
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Edema / drug therapy
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Heme Oxygenase (Decyclizing) / antagonists & inhibitors
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Heme Oxygenase (Decyclizing) / biosynthesis
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Heme Oxygenase (Decyclizing) / metabolism*
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Inflammation / immunology
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L-Lactate Dehydrogenase / metabolism
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Lipopolysaccharides
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Macrophages / enzymology
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Macrophages / immunology
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Metalloporphyrins / pharmacology
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Mice
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NF-E2-Related Factor 2 / metabolism
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / biosynthesis
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Protoporphyrins / pharmacology
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Quercetin / analogs & derivatives*
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Quercetin / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / metabolism
Substances
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Anti-Inflammatory Agents
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Antioxidants
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Cyclooxygenase 2 Inhibitors
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Lipopolysaccharides
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Metalloporphyrins
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NF-E2-Related Factor 2
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Nfe2l2 protein, rat
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Protoporphyrins
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Reactive Oxygen Species
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3-methylquercetin
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Nitric Oxide
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Quercetin
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tin protoporphyrin IX
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L-Lactate Dehydrogenase
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Nitric Oxide Synthase Type II
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Heme Oxygenase (Decyclizing)
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Hmox1 protein, rat
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Cyclooxygenase 2
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Ptgs2 protein, rat