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Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, ant...

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Autores principales: Novaes, Júlia T., Lillico, Ryan, Sayre, Casey L., Nagabhushanam, Kalyanam, Majeed, Muhammed, Chen, Yufei, Ho, Emmanuel A., Oliveira, Ana Luísa de P., Martinez, Stephanie E., Alrushaid, Samaa, Davies, Neal M., Lakowski, Ted M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750651/
https://www.ncbi.nlm.nih.gov/pubmed/29023392
http://dx.doi.org/10.3390/pharmaceutics9040045
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author Novaes, Júlia T.
Lillico, Ryan
Sayre, Casey L.
Nagabhushanam, Kalyanam
Majeed, Muhammed
Chen, Yufei
Ho, Emmanuel A.
Oliveira, Ana Luísa de P.
Martinez, Stephanie E.
Alrushaid, Samaa
Davies, Neal M.
Lakowski, Ted M.
author_facet Novaes, Júlia T.
Lillico, Ryan
Sayre, Casey L.
Nagabhushanam, Kalyanam
Majeed, Muhammed
Chen, Yufei
Ho, Emmanuel A.
Oliveira, Ana Luísa de P.
Martinez, Stephanie E.
Alrushaid, Samaa
Davies, Neal M.
Lakowski, Ted M.
author_sort Novaes, Júlia T.
collection PubMed
description Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.
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spelling pubmed-57506512018-01-10 Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids Novaes, Júlia T. Lillico, Ryan Sayre, Casey L. Nagabhushanam, Kalyanam Majeed, Muhammed Chen, Yufei Ho, Emmanuel A. Oliveira, Ana Luísa de P. Martinez, Stephanie E. Alrushaid, Samaa Davies, Neal M. Lakowski, Ted M. Pharmaceutics Article Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism. MDPI 2017-10-12 /pmc/articles/PMC5750651/ /pubmed/29023392 http://dx.doi.org/10.3390/pharmaceutics9040045 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Novaes, Júlia T.
Lillico, Ryan
Sayre, Casey L.
Nagabhushanam, Kalyanam
Majeed, Muhammed
Chen, Yufei
Ho, Emmanuel A.
Oliveira, Ana Luísa de P.
Martinez, Stephanie E.
Alrushaid, Samaa
Davies, Neal M.
Lakowski, Ted M.
Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title_full Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title_fullStr Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title_full_unstemmed Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title_short Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids
title_sort disposition, metabolism and histone deacetylase and acetyltransferase inhibition activity of tetrahydrocurcumin and other curcuminoids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750651/
https://www.ncbi.nlm.nih.gov/pubmed/29023392
http://dx.doi.org/10.3390/pharmaceutics9040045
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