Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.
Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have anti-tumor activities; however, the mechanism underlying its anti-tumorigenic effects is poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse resting macrophages. We found that UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex. These results demonstrate that UA stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappaB transactivation in the resting macrophages.
You
H J
HJ
Department of Pharmacy, College of Pharmacy, Chosun University, Kwangju, South Korea.
Choi
C Y
CY
Kim
J Y
JY
Park
S J
SJ
Hahm
K S
KS
Jeong
H G
HG
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D011485:Protein Binding; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D011112:Polymyxin B; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000097245:Ursolic Acid