Abstract
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 μM) effectively abolished NO generation from macrophages activated with lipopolysaccharide and interferon-γ. DHCD decreased the levels of protein and mRNA for inducible NO synthase (iNOS). DHCD potently blocked nuclear factor-κB (NF-κB) activation, a process necessary for transcriptional activation of iNOS. These results suggested that DHCD inhibited NO generation by blocking NF-κB activation and iNOS gene transcription. Because NF-κB 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.
Footnotes
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This research was supported by a special grant from Chung-Ang University.
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DOI: 10.1124/jpet.103.063693.
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ABBREVIATIONS. NO, nitric oxide; NOS, nitric-oxide synthase; iNOS, inducible nitric-oxide synthase; cNOS, constitutive nitric-oxide synthase; NF-κB, nuclear factor-κB; DHCD, 23,24-dihydrocucurbitacin D; IFNγ, interferon-γ; EMSA, electrophoretic mobility shift assay; RT, reverse transcription; PCR, polymerase chain reaction; LPS, lipopolysaccharide; G3PDH, glyceraldehyde-3-phosphage dehydrogenase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium.
- Received December 1, 2003.
- Accepted January 28, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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