Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide and cyclooxygenase-2 by chiisanoside via suppression of nuclear factor-kappaB activation in RAW 264.7 macrophage cells.
In the present study, the effects of several triterpenes isolated from the leaves of Acanthopanax chiisanensis (Araliaceae), namely, chiisanoside, isochiisanoside, 22-hydroxychiisanoside and chiisanogenin (the aglycone of chiisanoside) were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases. Taken together, our data indicate that the anti-inflammatory properties of chiisanoside might be the result from the inhibition of iNOS, COX-2, TNF-alpha and IL-1beta expression through the down-regulation of NF-kappaB binding activity.
Won
Jong-Heon
JH
Department of Biochemistry, College of Pharmacy, Kyung-Hee University; Seoul 130-701, South Korea.
Park
Sang-Yong
SY
Nam
Sang-Gil
SG
Park
Hee-Juhn
HJ
Choi
Jong-Won
JW
Lee
Kyung-Tae
KT
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000494:pharmacology*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017931:DNA Primers; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009844:Oligosaccharides; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C507583:chiisanoside; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases