TETRAHYDROCURCUMINOIDS: BIOACTIVE ANTIOXIDANT COMPOUNDS FROM CURCUMINOIDS

Lakshmi Prakash, Ph.D. & Muhammed Majeed, Ph.D.

Introduction

Tetrahydrocurcuminoids (THC)*is a colorless hydrogenated product derived from the yellow curcuminoids, the biologically active principles from the rhizomes of Curcuma longa (Turmeric), function as efficient antioxidant compounds. The superior antioxidant property of THC, combined with the lack of yellow color, render this product useful in achromatic food and cosmetic applications that currently employ conventional synthetic antioxidants1.

Curcuminoids are reported to be potent antioxidant compounds by virtue of their molecular structure1. THC have also shown significant antioxidant action in a number of in vitro and preclinical studies. Tetrahydrocurcuminoids are valued as the ultimate metabolites of the Curcuminoids in vivo 2. The poor circulating bioavailability3 of the parent curcuminoids, often attributed to their limited uptake due to poor water solubility, often impairs their biological effects in vivo. If supplied as their ultimate metabolites, this problem could be overcome. Substantial beneficial effects could be achieved with lower levels of these active metabolites as compared to the parent compounds. Several independent studies reported the significant antioxidant effects of the tetrahydrocurcuminoids 4,5,6.

Metabolism of curcumin

In an early study which elucidated the metabolic disposition of curcumin in rats, Curcumin labeled with deuterium and tritium was prepared. Oral and intraperitoneal doses of [3H]curcumin led to the fecal excretion of most of the radioactivity. The major biliary metabolites were glucuronides of tetrahydrocurcumin and hexahydrocurcumin. A minor biliary metabolite was dihydroferulic acid together with traces of ferulic acid. Metabolites were identified using chemical ionization mass spectrometry7.

A recent study2 investigated the pharmacokinetic properties of curcumin in mice and further clarified the nature of the metabolites of curcumin. Curcumin (0.1 g/kg) was administered intraperitoneally to mice and about 2.25 micrograms/ml appeared in the plasma in the first 15 minutes. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray technique.

* Patent Granted, U.S. Patent #5,861,415, and additional U.S. and Worldwide Patents Pending

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The chemical structures of these metabolites, determined by mass spectrometry, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates

Stability of curcumin and THC at physiological pH

The in vivo behavior of a biologically active compound depends much on its stability at physiological pH levels. In this context, the stability of curcumin and THC at different pH values was studied. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37C) (Figure 2). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo2.

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Figure 2: Stability of THC at Physiological pH

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