Chemical studies on antioxidant mechanism of garcinol: Analysis of radical reaction products of garcinol with peroxyl radicals and their antitumor activities

Antioxidant actions of garcinol (1), a polyisoprenylated benzophenone, purified from Garcinia indica fruit rind, are believed to contribute to its chemopreventive activity. However, the mechanisms of its antioxidant reactions remain unclear. The objective of this study was to characterize the reaction products of garcinol with peroxyl radicals generated by thermolysis of the azo initiator azo-bis-isobutyrylnitrile (AIBN). Structure elucidation of these products can provide insights into specific mechanisms of antioxidant reactions. Four reaction products (2-5) were isolated and identified. Their structures were determined on the basis of detailed high field 1D and 2D spectral analysis. The identification of these products provides the first unambiguous proof that the double bond of the isopentenyl group is a principal site of the antioxidant reaction of 1. The induction of apoptosis in human leukemia HL-60 cells, the inhibition of NO generation, and the inhibition of LPS-induced iNOS gene expression by Western blot analysis by 1 and its four oxidation products (2-5) were investigated. © 2002 Elsevier Science Ltd. All rights reserved.