Submitted to: Subtropical Technology Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/11/2006
Publication Date: 10/18/2006
Citation: Manthey, J.A. 2006. Results of several in vivo studies of the biological actions of 3,5,6,7,8,3',4'-heptamethoxyflavone from orange peel. Subtropical Technology Conference Proceedings. 57:20 Interpretive Summary:
Technical Abstract: The citrus polymethoxylated flavones inhibit the production of certain proinflammatory cytokines by bacterial lipopolysaccharide (LPS) stimulated monocytes. This inhibition has been shown to be due to the polymethoxylated flavone (PMF) inhibition of the phosphodiesterase-IV of the monocytes, an action that modulates the levels of intracellular cAMP, and consequently controls the signaling for cytokine production. A mouse study showed that intraperitoneal (ip) injection of 3,5,6,7,8,3’,4’-heptamethoxyflavone (HMF) significantly inhibited, in a dose-dependent manner, the production of the cytokine, tumor necrosis factor-' in LPS treated-mice. Levels of the inhibition of TNF- ' production were proportional to the serum levels of free HMF and its glucuronidated metabolites. The question remained whether the PMFs, mainly HMF, would also be active when administered orally. A recent study has shown that mice administered HMF orally at 50 and 100 mg/Kg body weight experienced no modulation of blood serum TNF- a levels compared to control animals. In contrast, mice administered HMF 100 mg/Kg (ip) showed an 11% decrease in blood serum TNF- ' levels. These results suggest that the presence of the nonmetabolized HMF after ip administration attenuates the cytokine production, while the glucuronidated metabolites lack this ability. This observation is consistent with the in vitro studies that showed that flavonoid glycosides were devoid of inhibitory activity in the LPS-stimulated human monocyte assay.