Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783289769854238720 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5750651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT novaesjuliat dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT lillicoryan dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT sayrecaseyl dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT nagabhushanamkalyanam dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT majeedmuhammed dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT chenyufei dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT hoemmanuela dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT oliveiraanaluisadep dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT martinezstephaniee dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT alrushaidsamaa dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT daviesnealm dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids AT lakowskitedm dispositionmetabolismandhistonedeacetylaseandacetyltransferaseinhibitionactivityoftetrahydrocurcuminandothercurcuminoids |