Next Article in Journal
Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems
Next Article in Special Issue
Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis
Previous Article in Journal / Special Issue
Altered Protein Expression of Cardiac CYP2J and Hepatic CYP2C, CYP4A, and CYP4F in a Mouse Model of Type II Diabetes—A Link in the Onset and Development of Cardiovascular Disease?
Article Menu

Export Article

Open AccessArticle
Pharmaceutics 2017, 9(4), 45; doi:10.3390/pharmaceutics9040045

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

1
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
2
College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT 84096, USA
3
Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA
4
Faculty of Science, School of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, Canada
5
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, USA
6
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada
These Authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 21 August 2017 / Revised: 5 October 2017 / Accepted: 11 October 2017 / Published: 12 October 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
View Full-Text   |   Download PDF [3734 KB, uploaded 13 October 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. View Full-Text
Keywords: curcumin; tetrahydrocurcumin; calebin-A; UHPLC–MS/MS; pharmacokinetics; antioxidant; anti-inflammatory; anticancer; HDAC; HAT curcumin; tetrahydrocurcumin; calebin-A; UHPLC–MS/MS; pharmacokinetics; antioxidant; anti-inflammatory; anticancer; HDAC; HAT
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Novaes, J.T.; Lillico, R.; Sayre, C.L.; Nagabushanam, K.; Majeed, M.; Chen, Y.; Ho, E.A.; Oliveira, A.L.P.; Martinez, S.E.; Alrushaid, S.; Davies, N.M.; Lakowski, T.M. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids. Pharmaceutics 2017, 9, 45.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top