The Naturally Occurring Flavolignan, Deoxypodophyllotoxin, Inhibits Lipopolysaccharide-Induced iNOS Expression through the NF-κB Activation in RAW264.7 Macrophage Cells

• Published in: Biological & pharmaceutical bulletin Vol. 31; no. 7; pp. 1312 - 1315
• Main Authors: Jin, Meihua, Moon, Tae Chul, Quan, Zhejiu, Lee, Eunkyung, Kim, Yun Kyung, Yang, Ju Hae, Suh, Seok-Jong, Jeong, Tae Cheon, Lee, Seung Ho, Kim, Cheorl-Ho, Chang, Hyeun Wook
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 01.07.2008
• Subjects: deoxypodophyllotoxin; electrophoretic mobility shift analysis; inducible nitric oxide synthase; nuclear factor-κB; pyrrolidinedithiocarbamate; RAW264.7 cell
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1312

Deoxypodophyllotoxin (DPT), a naturally occurring flavolignan with anti-inflammatory activity, was isolated from Anthriscus sylvestris HOFFM., and we examined its effects on the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated, murine macrophage-like RAW264.7 cells. Western blot analysis performed with specific anti-iNOS antibodies showed that a decrease in nitric oxide (NO) was accompanied by a decrease in the iNOS protein level. To clarify the mechanistic basis for DPT's ability to inhibit iNOS induction, we examined the effect of DPT on nuclear factor (NF)-κB transcriptional activity and DNA binding activity. DPT potently suppressed both reporter gene activity and DNA binding activity. These findings suggest that DPT in RAW264.7 cells abolished LPS-induced iNOS expression by inhibiting the transcription factor, NF-κB.