Calebin A: Analytical Development for Pharmacokinetics Study, Elucidation of Pharmacological Activities and Content Analysis of Natural Health Products

Authors

  • Ana Luísa de P. Oliveira College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Stephanie E. Martinez College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Kalyanam Nagabushnam Sabinsa Corporation, 20 Lake Drive, East Windsor NJ.
  • Muhammed Majeed Sabinsa Corporation, 20 Lake Drive, East Windsor NJ.
  • Samaa Alrushaid College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. http://orcid.org/0000-0001-7705-9025
  • Casey L. Sayre College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Neal M. Davies College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

DOI:

https://doi.org/10.18433/J32310

Abstract

Purpose: To develop a bioanalytical assay using RP-HPLC to quantify the curcuminoid calebin A, to characterize its pharmacokinetics in rats after intravenous (IV) and oral (PO) administration, to identify its pharmacological activities and to evaluate its content in natural health products. Methods: An RP-HPLC method was developed for the detection of calebin A. Separation was carried out using a Phenomenex® Kinetex® C18 column with UV detection at 339 nm. An isocratic mobile phase consisting of acetonitrile and water with 10 mM ammonium formate (pH 7.0) (40:60, v/v) at a flow rate of 0.8 mL/min was employed. Linear standard curves were established and applied in the pharmacokinetic study. Calebin A was administered to male Sprague-Dawley (CD) rats IV (20 mg/kg) or PO (500 mg/kg) (n=4/route of administration). Serum and urine samples were collected for 72 h post dose. In vitro antioxidant activity, anti-inflammatory activity (cyclooxygenase and lipoxygenase inhibition), dipeptidyl peptidase-4 (DPP-4) inhibition and cytochrome P450 inhibitory activties of calebin A were examined using commercial assay kits.  Content analysis of calebin A in 14 natural health products advertised to contain  turmeric were carried out using methanolic extraction. Results: The HPLC method was successfully applied to a pharmacokinetic study of calebin A in rats. After IV and PO administration of calebin A, the compound was detected as the aglycone and a glucuronidated metabolite. Oral bioavailabitily was found to be ~0.5%, serum half-life was ~1-3 h. Calebin A appears to be primarily excreted via non-renal routes. Calebin A possessed concentration-dependent antioxidant activity and DPP-4 inhibition. Calebin A appears to be a non-selective cyclooxygenase inhibitor and also a poor lipoxygenase inhibitor. The curcuminoid displayed  in vitro interactions with  CYP2D6 and CYP1A2. Content analysis of 14  natural health products that claimed to contain turmeric showed that concentration of calebin A was inconsistent among the products. Conclusion: A successful assay was developed for the detection of calebin A using RP-HPLC. Preliminary pharmacokinetic studies indicate that an unoptimised formulation of calebin A has poor oral bioavailability. Calebin A exhibits  various pharmacological activities.

 

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Author Biography

Samaa Alrushaid, College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

PhD student Faculty of Health Sciences College of Pharmacy

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Published

2015-10-12

How to Cite

Oliveira, A. L. de P., Martinez, S. E., Nagabushnam, K., Majeed, M., Alrushaid, S., Sayre, C. L., & Davies, N. M. (2015). Calebin A: Analytical Development for Pharmacokinetics Study, Elucidation of Pharmacological Activities and Content Analysis of Natural Health Products. Journal of Pharmacy & Pharmaceutical Sciences, 18(4), 494–514. https://doi.org/10.18433/J32310

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CLOSED. Special Issue - Chief Guest Editor: Basil D Roufogalis; Co-Guest Editors: Emanuel Strehler & Srinivas Nammi