Icariin: a special antioxidant to protect linoleic acid against free-radical-induced peroxidation in micelles

The objective in this work is to determine the antioxidant capacity and effectiveness of icariin (2-(4'-methoxylphenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3'-methyl-2-butylenyl)-4-chromanone), the major component in herba epimedii being used widely in traditional Chinese medicine for the treatment of artherosclerosis and neuropathy, in which 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced peroxidation of linoleic acid (LH) in sodium dodecyl sulfate (SDS) acts as the experimental system. By containing an intramolecular hydrogen bond, icariin protects LH against AAPH-induced peroxidation of LH only in SDS, an anionic micelle. The number of trapping peroxyl radicals (LOO(*)), n, by icariin is just 0.0167 whereas alpha-tocopherol (TOH) and L-ascorbyl-6-laurate (VC-12) are 2.14 and 1.25, respectively, with reference to the n of 6-hydroxyl-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), 2.00. This is also related to how the intramolecular hydrogen bond enhances the bond dissociation enthalpy (BDE) of O-H in icariin. However, calculation of the inhibition rate constant, k(inh), a kinetic parameter to describe the reaction between the antioxidant and LOO(*), results in a k(inh) of icariin at about one magnitude larger than those of Trolox, TOH, and VC-12. This fact reveals that, by the view of kinetics, icariin is an antioxidant with much higher effectiveness. In addition, the antioxidant capacities of icariin used together with other antioxidants have been determined and the results indicate that the n of icariin decreases markedly while the n values of Trolox and TOH increase, even if the n of icariin is a negative value in the presence of VC-12. Furthermore, an analysis of k(inh) in this case reveals that the k(inh)(icariin) increases nearly one magnitude with the decrease of k(inh)(Trolox) and no remarkable change occurs for k(inh)(TOH). The negative value of k(inh)(icariin) in the presence of VC-12 can be regarded as the icariin functions as a prooxidant that can be rectified by VC-12 effectively. These findings implicate that the evaluation of antioxidant activity should not only focus on an n value, a thermodynamic possibility, but k(inh) and the charge property of the micelle should be also taken into account. To some extent, the latter factors are more important than the thermodynamic possibility.