Antioxidant activity of piperlactam S: prevention of copper-induced LDL peroxidation and amelioration of free radical-induced oxidative stress of endothelial cells.
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 microM) 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.
Tsai
Jeng-Yan
JY
Institute of Pharmacology, School of Life Sciences, National Yang-Ming University, Taipei, ROC.
Chou
Cheng-Jeng
CJ
Chen
Chieh-Fu
CF
Chiou
Wen-Fei
WF
D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D003300:Copper / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007769:Lactams / Q000302:isolation & purification / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D031701:Piper / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D005609:Free Radicals; D007769:Lactams; D008077:Lipoproteins, LDL; C415282:piperlactam S; D003300:Copper