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

Authors :
Júlia T. Novaes
Ryan Lillico
Casey L. Sayre
Kalyanam Nagabushanam
Muhammed Majeed
Yufei Chen
Emmanuel A. Ho
Ana Luísa de P. Oliveira
Stephanie E. Martinez
Samaa Alrushaid
Neal M. Davies
Ted M. Lakowski
Source :
Pharmaceutics, Vol 9, Iss 4, p 45 (2017)
Publication Year :
2017
Publisher :
MDPI AG, 2017.

Abstract

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.

Details

Language :
English
ISSN :
19994923
Volume :
9
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.2b405f6be5b94c3493e7a516c715b867
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics9040045