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: Kyuhwa Seo, Ji Hye Yang, Sang Chan Kim, Sae Kwang Ku, Sung Hwan Ki, Sang Mi Shin
• Journal: Inflammation (Inflammation) Vol. 37 Issue 3 Pg. 712-22 (Jun 2014) ISSN: 1573-2576 [Electronic] United States
• PMID: 24337631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Cyclooxygenase 2 Inhibitors
• Lipopolysaccharides
• Metalloporphyrins
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Protoporphyrins
• Reactive Oxygen Species
• 3-methylquercetin
• Nitric Oxide
• Quercetin
• tin protoporphyrin IX
• L-Lactate Dehydrogenase
• Nitric Oxide Synthase Type II
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Active Transport, Cell Nucleus (drug effects)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cyclooxygenase 2 (biosynthesis)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Edema (chemically induced, drug therapy)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors, biosynthesis, metabolism)
• Inflammation (immunology)
• L-Lactate Dehydrogenase (metabolism)
• Lipopolysaccharides
• Macrophages (enzymology, immunology)
• Metalloporphyrins (pharmacology)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (biosynthesis)
• Protoporphyrins (pharmacology)
• Quercetin (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)