Free Radical Reactions of Curcumin in Membrane Models

https://doi.org/10.1016/S0891-5849(97)00026-9Get rights and content

Abstract

Free radical reactions of curcumin, a lipid soluble antioxidant from turmeric (Curcuma longa), have been studied with a variety of oxidants using TX 100 micelle as a model membrane. The phenoxyl radicals of curcumin generated by one electron oxidizing azide radicals in acetonitrile-water mixture and TX 100 micelles show very similar spectral behavior. However, in membrane models the radical lifetimes and the molar extinction coefficients are significantly different from the homogeneous solutions. Micellized curcumin reacts with haloperoxyl radicals, superoxide, and lipid peroxyl radicals with rate constants of 5 × 108, 4.6 × 104, and 5.3 × 105 M−1s−1, respectively. Curcumin derived phenoxyl radicals decay by radical-radical reactions in homogeneous solutions, while in the micelles, radical decay is mostly first order when the average occupancy of the micelle is less than 1. Implications of these results in evaluating curcumin as an antioxidant is discussed.

Introduction

Dietary antioxidants are known to decrease the risk of many chronic diseases such as cancer and cardiovascular disorders.1, 2 The antioxidant activity may be a result of one of the following: specific scavenging of reactive free radicals or scavenging of oxygen containing compounds such as hydrogen peroxide or, chelation to metals. Curcumin is a natural antioxidant derived from turmeric (Curcuma longa) known to possess therapeutic properties since ancient times. It shows a variety of pharmacological activities such as antiinflammatory, anticarcinogenic, and antioxidant properties.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 Curcumin and its analogues are known to protect biomembranes against peroxidative damage. Peroxidation of lipids is known to be a free radical-mediated chain reaction leading to the damage of the cell membranes, and the inhibition of peroxidation by curcuminoids is mainly attributed to the scavenging of the reactive free radicals involved in the peroxidation. Most of the natural antioxidants possess either a phenolic function or a β-diketone group. Curcumin and its analogues are unique, having both phenolic and β-diketone functional groups on the same molecule. Like vitamin E (α-tocopherol), curcumin is a lipid soluble antioxidant and is believed to be localized within the membranous subcellular fraction of cells. To simulate the natural environment of the membranes we have used a nonionic aqueous surfactant Triton X-100 (TX-100) as a model for membrane. Free radical reactions of lipid soluble antioxidants in TX-100 micelles have been previously studied by several authors.15, 16, 17 Micelles have a hydrophobic core dispersed in the aqueous phase that solubilizes lipophillic molecules. To understand the reactivity of curcumin with the reactive free radicals when solubilised in the membrane, reactions of curcumin have been studied with a variety of oxidants.

Section snippets

Materials

Curcumin and linoleic acid from Sigma, and TX-100 from Aldrich, were used as received. Gases used were from British Oxygen Co. All other chemicals were of highest purity available and were used without further purification. Solutions were prepared in water from a ‘Milli-Q’ system (Millipore).

Methods

Curcumin (I) is practically insoluble in water. Its solubility in micellar systems was achieved by continuous stirring of curcumin (50 to 200 μM) in 10–50 mM aqueous TX-100 solutions. The critical micelle

Curcumin-TX-100 Binding Constant

Binding and micellisation of curcumin with TX-100 was determined by following the change in absorption intensity of curcumin (25 μM) at 425 nm with TX-100 concentration (200 μM to 5 mM) and a value of 6.0 ± 0.3 × 103 M−1 was estimated.

Reaction With Azide Radical

Gorman et al.[24] reported formation of phenoxyl radicals of curcumin on monoelectron oxidation by radiolytically generated azide radicals in 1:4 mixture of acetonitrile and aqueous phosphate buffer. We studied the reaction of azide radicals with curcumin in

Discussion

Phenoxyl radicals of curcumin absorbing at 500 nm were generated by the reaction of model oxidizing radicals and several biologically important oxidants. The radicals of curcumin would be resonance stabilized due to several possible tautomeric forms, along the extended conjugated system of double bonds. The extinction coefficients of the radicals are much higher in micellar solutions compared to homogeneous solutions like acetonitrile and water mixtures, probably due to the different micro

Acknowledgements

The author expresses sincere thanks to Prof P. Wardman, Dr. L. P. Candeias, Prof. M. N. A. Rao, Dr. T. P. A. Devasagayam, Dr. Sreejayan, Dr. C. Gopinathan, Dr. T. Mukherji, and Dr. A. V. Sapre for many useful discussions.

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