lignans and cumene-hydroperoxide

The antioxidant properties of sesame lignans (sesamol, sesamin and sesamolin) were evaluated in comparison to tocols (alpha- and gamma-tocopherols and alpha-tocotrienol) and butylated hydroxytoluene (BHT) using the following in vitro lipid peroxidation systems: (i) rat liver microsomes and cumene hydroperoxide (CumOOH)/Fe2+-ADP-NADPH (enzymatic) or (ii) rat liver mitochondria and Fe2+-ascorbate (nonenzymatic) systems. Sesamol containing a free phenolic group inhibited lipid peroxidation in both the systems whereas sesamin and sesamolin having methylenedioxy groups were effective only in the microsomal system. Since detoxifying enzymes are localized in microsomes, the inhibitory effects of sesamin and sesamolin observed in the microsomal system may be attributed to their metabolites. However, the inhibitory effects of lignans were lower than tocols and BHT. Combination of individual lignans and tocopherols (alpha, gamma) or alpha-tocotrienol showed higher inhibitory effects than the sum of individual inhibitions in CumOOH and Fe2+-ascorbate systems suggesting synergistic interactions. The time course of CumOOH-mediated lipid peroxidation showed a lag period and a decreased rate of thiobarbituric acid reactive product formation in the presence of individual lignans in combination with alpha-tocopherol suggesting recycling of alpha-tocopherol.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Drug Synergism; Kinetics; Lignans; Lipid Peroxidation; Male; Microsomes, Liver; Mitochondria, Liver; Rats; Rats, Wistar; Sesamum; Structure-Activity Relationship; Thiobarbituric Acid Reactive Substances; Tocopherols; Vitamin E

The antioxidant/photoprotective potential of a standardized Krameria triandra (KT) root extract (15% neolignans) has been evaluated in different cell models, rat erythrocytes and human keratinocytes cell lines, exposed to chemical (cumene hydroperoxide, CuOOH) and physical (UVB radiation) free radical inducers. The extract was significantly more active (IC50 0.28 +/- 0.04 microg/ml) than the typical chain-breaking antioxidant alpha-tocopherol (IC50 = 6.37 +/- 0.41 microg/ml) in inhibiting the CuOOH-induced hemolysis in rat blood cells. The KT constituent 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, was the most active (IC50 = 0.03 +/- 0.005 microg/ml), followed by eupomatenoid 6 (IC50 = 0.29 +/- 0.06 microg/ml) and conocarpan (IC50 = 0.77 +/- 0.08 microg/ml). The same order of potency was observed in red blood cells exposed to UVB irradiation in continuo, with IC50 values 0.78 +/- 0.08 microg/ml for KT extract, 0.18 +/- 0.02 microg/ml for 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, 0.95 +/- 0.11 microg/ml for eupomatenoid 6, and 3.8 +/- 0.39 microg/ml for conocarpan. In cultured human keratinocytes exposed to UVB radiation (50 mJ/cm2), KT extract (2.5-20 microg/ml) significantly and dose-dependently restrained the loss in cell viability and the intracellular oxidative damage: glutathione (GSH) depletion and the rise in dichlorofluorescein (DCF), marker of peroxide accumulation, were suppressed by 20 microg/ml KT and in parallel cell morphology maintained. The cytoprotective effect of the extract was confirmed in a more severe model of cell damage: exposure of keratinocytes to higher UVB doses (300 mJ/cm2), which induce a 50% cell death. In keratinocyte cultures supplemented with 10 microg/ml, cell viability was almost completely preserved and more efficiently than with (-)-epigallocatechin 3-gallate and green tea. The results of this study indicate the potential use of Rhatany extracts, standardized in neolignans, as topical antioxidants/radical scavengers against skin photodamage.

Topics: Animals; Antioxidants; Benzene Derivatives; Benzofurans; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Erythrocytes; Furans; Humans; Inhibitory Concentration 50; Keratinocytes; Lignans; Magnoliopsida; Male; Phenols; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Sunscreening Agents; Ultraviolet Rays