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Pharmaceutics. 2017 Oct 12;9(4). pii: E45. doi: 10.3390/pharmaceutics9040045.

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

Author information

1
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. juliatnovaes@gmail.com.
2
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. umLillic@myumanitoba.ca.
3
College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT 84096, USA. csayre@roseman.edu.
4
Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. kalyanam@sabinsa.com.
5
Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. mmjd52@hotmail.com.
6
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. umche355@myumanitoba.ca.
7
Faculty of Science, School of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, Canada. emmanuel.ho@uwaterloo.ca.
8
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. analuisapoliv@gmail.com.
9
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, USA. smartinez@vetmed.wsu.edu.
10
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. umalrush@myumanitoba.ca.
11
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada. ndavies@ualberta.ca.
12
The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. ted.lakowski@umanitoba.ca.

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.

KEYWORDS:

HAT; HDAC; UHPLC–MS/MS; anti-inflammatory; anticancer; antioxidant; calebin-A; curcumin; pharmacokinetics; tetrahydrocurcumin

Conflict of interest statement

This work was partially funded by the Sabinsa Corporation to Neal M. Davies and the authors Kalyanam Nagabushnam and Muhammed Majeed are employed with this company that supplied the tetrahydrocurcumin, curcumin and calebin-A materials for this study. All other authors declare no conflicts of interest. The authors alone are responsible for the content, writing, and interpretations in this paper.

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