O-Methylated flavonol isorhamnetin prevents acute inflammation through blocking of NF-κB activation.

Abstract

Here, we isolated isorhamnetin, a natural 3'-O-methylated flavonoid, from water dropwort (Oenanthe javanica, Umbelliferae) and investigated its ability to protect against acute inflammation in vivo and in vitro. To induce paw swelling, the hind paw of each rat was injected with a carrageenan 1h after vehicle or isorhamnetin treatment. In vitro effect and mechanism studies were performed in lipopolysaccharide (LPS)-activated macrophages. Administration of isorhamnetin markedly inhibited the swelling volume and the thickness of hind paws. Moreover, isorhamnetin significantly reduced inflammatory cell infiltration and pro-inflammatory gene expression in rats. Isorhamnetin pretreatment inhibited inducible nitric oxide synthase (iNOS) expression and NO release in LPS-stimulated cells. Activation of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) is the key step in the iNOS gene induction. Isorhamnetin specifically inhibited NF-κB luciferase activity, but not AP-1. Pretreatment with isorhamnetin suppressed NF-κB nuclear translocation in accordance with decreased phosphorylation and degradation of inhibitory-κB. Consistently, TNF-α, IL-1β and IL-6 expression, representative NF-κB target genes, were almost completely prohibited by isorhamnetin. Furthermore, isorhamnetin inhibited LPS-induced JNK and AKT/IKKα/β phosphorylation. Our results suggest that isorhamnetin inhibited JNK, and AKT/IKKα/β activation, leading to NF-κB inactivation, which might contribute to the inhibition of the acute inflammatory response.

• Authors: Ji Hye Yang, Sang Chan Kim, Bo Yeon Shin, So Hee Jin, Mi Jeong Jo, Kyung Hwan Jegal, Young Woo Kim, Jong Rok Lee, Sae Kwang Ku, Il Je Cho, Sung Hwan Ki
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 59 Pg. 362-72 (Sep 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23774260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• NF-kappa B
• 3-methylquercetin
• Quercetin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, isolation & purification, pharmacology, therapeutic use)
• Cell Line, Transformed
• Cell Nucleus (drug effects, immunology, metabolism, pathology)
• Disease Models, Animal
• Edema (immunology, metabolism, pathology, prevention & control)
• Ethnopharmacology
• Lymphocyte Activation (drug effects)
• Macrophage Activation (drug effects)
• Macrophages (drug effects, immunology, metabolism)
• Male
• Medicine, East Asian Traditional
• Mice
• NF-kappa B (antagonists & inhibitors, genetics, metabolism)
• Oenanthe (chemistry)
• Protein Transport (drug effects)
• Quercetin (analogs & derivatives, chemistry, isolation & purification, pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Republic of Korea
• Skin (drug effects, immunology, metabolism, pathology)