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Chem Biol Interact. 2010 Mar 30;184(3):366-75. doi: 10.1016/j.cbi.2010.02.005. Epub 2010 Feb 10.

Protective effects of diosgenin in the hyperlipidemic rat model and in human vascular endothelial cells against hydrogen peroxide-induced apoptosis.

Author information

1
Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.

Abstract

Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-associated conditions in cardiovascular diseases. Oxidative stress, as a main risk factor causes vascular endothelial cell apoptosis, which is implicated in the pathogenesis of cardiovascular disorders. Diosgenin, an aglycone of steroidal saponins, has been reported to exert anti-proliferative and proapoptotic actions on cancer cells widely. In this study, we propose that diosgenin can protect the hyperlipidemic rats and prevent endothelial apoptosis under oxidative stress. We investigated the hypolipidemic and antioxidative effects of diosgenin on rats fed with high cholesterol and high fat diet for 6 weeks. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), glutathione peroxidase (GSH-PX), nitric oxide synthase (NOS), hepatic malondialdehyde (MDA), lipoprotein lipase (LPL), hepaticlipase (HL) and superoxide dismutase (SOD) activities were evaluated. Then we explored the effects and mechanism of diosgenin against hydrogen peroxide-induced apoptosis of human vein endothelium cells (HUVECs). Intracellular reactive oxygen species (ROS), glutathione (GSH), nitric oxide (NO), DNA fragment formation and mitochondrial membrane potentials (DeltaPsim) were determined. Diosgenin treatment increased LPL, HL, SOD, GSH-PX and NOS activities, thus attenuated oxygen free radicals, decreased MDA, TC, TG and LDL-C levels in hyperlipidemic rats. Diosgenin pretreatment significantly attenuated H(2)O(2)-induced apoptosis in HUVECs, intracellular ROS, GSH depletion, DNA fragment formation, and restored NO, DeltaPsim. These results suggested that diosgenin is a very useful compound to control hyperlipidemia by both improving the lipid profile and modulating oxidative stress and prevent H(2)O(2)-induced apoptosis of HUVECs, in partly through regulating mitochondrial dysfunction pathway.

PMID:
20149787
DOI:
10.1016/j.cbi.2010.02.005
[Indexed for MEDLINE]

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