Polymethoxylated Flavones Derived from Citrus Suppress Tumor Necrosis Factor-α Expression by Human Monocytes
| Autor: | Carl L. Manthey, Karel Grohmann, Kevin Ash, Antonio Montanari, John A. Manthey |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Citrus Phosphodiesterase Inhibitors medicine.medical_treatment Flavonoid Pharmaceutical Science In Vitro Techniques Pharmacology Biology Flavones Monocytes Analytical Chemistry Drug Discovery Cyclic AMP medicine Humans RNA Messenger Phosphodiesterase inhibitor IC50 Flavonoids chemistry.chemical_classification Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Monocyte Organic Chemistry Biological activity Cytokine medicine.anatomical_structure Complementary and alternative medicine chemistry Biochemistry Molecular Medicine Tumor necrosis factor alpha |
| Zdroj: | Journal of Natural Products. 62:441-444 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | Flavonoids isolated from citrus were evaluated for their ability to affect the inflammation response through suppression of cytokine expression by human monocytes. Several polymethoxylated flavones inhibited lipopolysaccharide-induced monocyte expression of tumor necrosis factor (TNFalpha). Subsequent studies centered on the compound 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) which produced the highest inhibition (IC50 = 5 microM). HMF was also a potent inhibitor of macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-10 (IL-10) production, but not of IL-1beta, IL-6, or IL-8 production. Suppression of TNFalpha production was at the level of mRNA induction as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). HMF was also a potent inhibitor of human phosphodiesterase activity and was shown to induce a substantial elevation of cAMP levels in monocytes. The similarity of these results to the inhibition profile of the known phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, suggests that the polymethoxylated flavones inhibit cytokine production in part by suppression of phosphodiesterase activity. The ability of HMF to also inhibit IL-10 production suggests the additional existence of a phosphodiesterase-independent mechanism for this compound. |
| Databáze: | OpenAIRE |
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