Antioxidant Activity of Piperlactam S: Prevention of Copper-Induced LDL Peroxidation and Amelioration of Free Radical-Induced Oxidative Stress of Endothelial Cells

Abstract

The protective effects of piperlactam S, an alkaloid isolated from Piper kadsura (Choisy) Ohwi, on lipid peroxidation and free radical-mediated cell injuries were investigated. Piperlactam S (1 to 20 μM) concentration-dependently prevented the copper-catalyzed oxidative modification of human low-density lipoproteins (LDL) measured through (i) the lag period, (ii) the slope of the propagation phase, (iii) the total amount of conjugated dienes formed, and (iv) the electrophoretic mobility of LDL. Fe²⁺-induced oxidative modification of cell membrane was also significantly attenuated by piperlactam S as measured by thiobarbituric acid-reactive substances (TBARS). Furthermore, piperlactam S effectively minimized the loss of cell viability induced by Fenton’s reagent (H₂O₂/FeSO₄) in cultured endothelial cells and significantly reversed H₂O₂/FeSO₄-induced impairment of endothelium-dependent relaxation to acetylcholine in rat aorta. Since the oxidative modification of LDL plays an important role in the genesis of atherosclerosis, piperlactam S may help to reduce the risk of atherosclerosis, not only by protecting LDL and membrane lipids from oxidative modification but also by reducing free radical-induced endothelial injury and/or dysfunction.

Abbreviations

LDL:low-density lipoprotein

MDA:malondialdehyde

PAECs:pulmonary artery endothelial cells

PE:phenylephrine

REM:relative electrophoretic mobility

TBARS:thiobarbituric acid-reactive substances

Piper kadsura (Choisy) Ohwi - Piperaceae - piperlactam S - low-density lipoprotein - TBARS - endothelial cells - free radicals - cytotoxicity

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