| In vitro: |
| J Agric Food Chem. 2004 Sep 22;52(19):5869-72. | | Identification of centrolobol as the platyphylloside metabolite responsible for the observed effect on in vitro digestibility of hay.[Pubmed: 15366834] |
METHODS AND RESULTS:
Syntheses of the metabolites from platyphylloside, a phenol causing digestibility inhibition in rumen fluid, have been performed to identify the active metabolite. 1,7-Bis(4'-hydroxyphenyl)-3-heptanone (3-platyphyllone), racemic, and the two enantiomers of 1,7-bis(4'-hydroxyphenyl)-3-heptanol (Centrolobol) and 1,7-bis(4-hydroxyphenyl)heptane (platyphyllane) were synthesized and tested regarding digestibility inhibition in vitro in cow rumen fluid.
CONCLUSIONS:
All compounds tested induced a decreased digestion. Centrolobol was found to be the metabolite causing the observed effect, and (R)-Centrolobol was found to be the enantiomer formed in the rumen liquor in vitro. | | Planta Med. 2015 Feb;81(3):222-7. | | Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically enhances the anticancer activity of HDAC inhibitor in HT29 cells.[Pubmed: 25590368] | The identification of new isoform-specific histone deacetylase inhibitors is important for revealing the biological functions of individual histone deacetylase and for determining their potential use as therapeutic agents. Among the 11 zinc-dependent histone deacetylases that have been identified in humans, histone deacetylase 6 is a structurally and functionally unique enzyme.
METHODS AND RESULTS:
Here, we tested the inhibitory activity of diarylheptanoids isolated from Betula platyphylla against histone deacetylase 6. Aceroside VIII selectively inhibited histone deacetylase 6 catalytic activity and the combined treatment of aceroside VIII or (-)-centrolobol with A452, another selective histone deacetylase 6 inhibitor, led to a synergistic increase in levels of acetylated α-tubulin. Aceroside VIII, paltyphyllone, and (-)-centrolobol synergistically enhanced the induction of apoptosis and growth inhibition by A452. Consistent with these results, A452 in combination with aceroside VIII, paltyphyllone, or (-)-centrolobol was more potent than either drug alone for the induction of apoptosis.
CONCLUSIONS:
Together, these findings indicate that aceroside VIII is a specific histone deacetylase 6 inhibitor and points to a mechanism by which natural histone deacetylase 6-selective inhibitors may enhance the efficacy of other histone deacetylase 6 inhibitors in colon cancer cells. |
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