Inhibition of nitric oxide generation by 23,24-dihydrocucurbitacin D in mouse peritoneal macrophages.
Nitric oxide (NO) has various physiological functions. However, uncontrolled overproduction of NO can be toxic in many pathologic conditions involving inflammatory tissue damage. In the present study, we examined effects of 23,24-dihydrocucurbitacin D (DHCD) isolated from the root of Bryonia alba L. on macrophage NO generation. DHCD (<80 microM) effectively abolished NO generation from macrophages activated with lipopolysaccharide and interferon-gamma. DHCD decreased the levels of protein and mRNA for inducible NO synthase (iNOS). DHCD potently blocked nuclear factor-kappaB (NF-kappaB) activation, a process necessary for transcriptional activation of iNOS. These results suggested that DHCD inhibited NO generation by blocking NF-kappaB activation and iNOS gene transcription. Because NF-kappaB activation is necessary not only for NO generation but also for many inflammatory processes, DHCD and its derivatives could be developed as anti-inflammatory drugs.
Park
Chang Seok
CS
Department of Biochemistry, College of Medicine, Chung-Ang University, Dongjakgu, Seoul, Korea.
Lim
Hyun
H
Han
Kee Jung
KJ
Baek
Sun Heum
SH
Sohn
Hyung Ok
HO
Lee
Dong Wook
DW
Kim
Yang-Gyun
YG
Yun
Hye-Young
HY
Baek
Kwang Jin
KJ
Kwon
Nyoun Soo
NS
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D014315:Triterpenes / Q000494:pharmacology*
D016328:NF-kappa B; D014315:Triterpenes; D009569:Nitric Oxide; C038105:cucurbitacin D; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse