Isorhamnetin-3-O-Glucuronide Suppresses JNK and p38 Activation and Increases Heme-Oxygenase-1 in Lipopolysaccharide-Challenged RAW264.7 Cells.
Preclinical Research Isorhanmetin (ISH) exhibits a wide range of biological properties including anticancer, anti-oxidant and anti-inflammatory activities. However, the pharmacological properties of isorhamnetin-3-O-glucuronide (IG), a glycoside derivative of ISH, have not been extensively examined. The objective of this study was to examine the anti-inflammatory properties of IG and its underlying mechanism in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells in comparison with its aglycone, ISH. IG suppressed LPS-induced extracellular secretion of the proinflammatory mediators, nitric oxide (NO) and PGE2 , and proinflammatory protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2. IG also increased expression of heme oxygenase-1 (HO-1). IG attenuated LPS-induced activation of c-Jun N-terminal kinase (JNK) and p38 in a concentration-dependent manner with negligible suppression of extracellular signal-regulated kinases (ERK) phosphorylation. In conclusion, this study demonstrates that IG exerts anti-inflammatory activity by increasing HO-1 expression and by suppressing JNK and p38 signaling pathways in LPS-challenged RAW264.7 macrophage cells. Drug Dev Res 77 : 143-151, 2016. © 2016 Wiley Periodicals, Inc.
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Jin-Young
JY
Park
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Song-In
SI
Kim
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Hee Jae
HJ
Lee
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Sung-Soo
SS
Kim
College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea.
Yong-Soo
YS
Kwon
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Wanjoo
W
Chun
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067996:RAW 264.7 Cells
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C047368:3-methylquercetin; D011794:Quercetin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
HO-1; RAW264.7 cells; c-Jun N-terminal kinase; cyclooxygenase-2; inducible nitric oxide synthase; isorhamnetin-3-O-glucuronide; lipopolysaccharide; p38