Synthetic cryptolepine inhibits DNA binding of NF-κB

Olumayokun A. Olajide, Elke H. Heiss, Daniel Schachner, Colin W. Wright, Angelika M. Vollmar, Verena M. Dirsch

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The alkaloid cryptolepine is thought to mediate the anti-inflammatory effects of the climbing shrub, Cryptolepis sanguinoleta. The underlying mechanism of action, however, is largely unknown. In the present study, we show that the synthetic cryptolepine-hydrochloride (2.5-10 μM) dose-dependently inhibits lipopolysaccharide (LPS)-induced nitric oxide production in the murine macrophage cell line RAW 264.7. We furthermore demonstrate a strong inhibition of nuclear factor (NF)-κB, a transcription factor primarily involved in inflammatory and immune responses, by cryptolepine (2.5-10 μM) using a luciferase reporter gene assay in human HEK 293 cells. Examining the individual steps of NF-κB activation in the presence of cryptolepine we could exclude an inhibitory effect on degradation of IκB or nuclear translocation of NF-κB by the alkaloid. However, EMSA of nuclear extracts from LPS-activated RAW cells revealed reduced DNA binding activity of NF-κB by cryptolepine in vivo and in vitro. This indicates that cryptolepine may exhibit its anti-inflammatory action by blocking DNA binding of activated NF-κB and thus transcription of NF-κB-regulated proinflammatory proteins.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number1
DOIs
Publication statusPublished - 1 Jan 2007
Externally publishedYes

Fingerprint

DNA
Alkaloids
Cryptolepis
Lipopolysaccharides
Anti-Inflammatory Agents
Transcription Factors
Macrophages
HEK293 Cells
Transcription
Luciferases
Reporter Genes
cryptolepine
Assays
Nitric Oxide
Genes
Chemical activation
Cells
Degradation
Proteins

Cite this

Olajide, O. A., Heiss, E. H., Schachner, D., Wright, C. W., Vollmar, A. M., & Dirsch, V. M. (2007). Synthetic cryptolepine inhibits DNA binding of NF-κB. Bioorganic and Medicinal Chemistry, 15(1), 43-49. https://doi.org/10.1016/j.bmc.2006.10.018
Olajide, Olumayokun A. ; Heiss, Elke H. ; Schachner, Daniel ; Wright, Colin W. ; Vollmar, Angelika M. ; Dirsch, Verena M. / Synthetic cryptolepine inhibits DNA binding of NF-κB. In: Bioorganic and Medicinal Chemistry. 2007 ; Vol. 15, No. 1. pp. 43-49.
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Olajide, OA, Heiss, EH, Schachner, D, Wright, CW, Vollmar, AM & Dirsch, VM 2007, 'Synthetic cryptolepine inhibits DNA binding of NF-κB', Bioorganic and Medicinal Chemistry, vol. 15, no. 1, pp. 43-49. https://doi.org/10.1016/j.bmc.2006.10.018

Synthetic cryptolepine inhibits DNA binding of NF-κB. / Olajide, Olumayokun A.; Heiss, Elke H.; Schachner, Daniel; Wright, Colin W.; Vollmar, Angelika M.; Dirsch, Verena M.

In: Bioorganic and Medicinal Chemistry, Vol. 15, No. 1, 01.01.2007, p. 43-49.

Research output: Contribution to journalArticle

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AU - Olajide, Olumayokun A.

AU - Heiss, Elke H.

AU - Schachner, Daniel

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AU - Vollmar, Angelika M.

AU - Dirsch, Verena M.

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