2. Academic Validation
  3. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

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

  • Pharmaceutics. 2017 Oct 12;9(4):45. doi: 10.3390/pharmaceutics9040045.
Júlia T Novaes 1,  Ryan Lillico 2,  Casey L Sayre 3,  Kalyanam Nagabushnam 4,  Muhammed Majeed 5,  Yufei Chen 6,  Emmanuel A Ho 7,  Ana Luísa de P Oliveira 8,  Stephanie E Martinez 9,  Samaa Alrushaid 10,  Neal M Davies 11,  Ted M Lakowski 12
Affiliations

Affiliations

  • 1 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
  • 2 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
  • 3 College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT 84096, USA. [email protected].
  • 4 Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. [email protected].
  • 5 Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. [email protected].
  • 6 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
  • 7 Faculty of Science, School of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, Canada. [email protected].
  • 8 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
  • 9 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, USA. [email protected].
  • 10 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
  • 11 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada. [email protected].
  • 12 The Rady Faculty of Health Sciences, College of Pharmacy, Pharmaceutical Analysis Laboratory, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. [email protected].
PMID: 29023392 DOI: 10.3390/pharmaceutics9040045
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.

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