Crude extracts of Solanum lyratum protect endothelial cells against oxidized low-density lipoprotein-induced injury by direct antioxidant action.
BACKGROUND
Oxidized low-density lipoprotein (oxLDL) is a proatherogenic molecule that accumulates in the vascular wall and contributes to the pathogenesis of vascular dysfunction early in the development of atherosclerosis. The whole plant of Solanum lyratum is a traditional Chinese medicine that has been used for centuries to treat cancer, tumors, and herpes. However, the cellular and molecular mechanisms of its antioxidant effects are still largely unknown. This study tested the hypothesis that Solanum lyratum Thunberg extract (SLE) could block oxLDL-induced endothelial dysfunction in cultured human umbilical vein endothelial cells (HUVECs). Possible mechanisms were explored.


METHODS
Antioxidative activities of SLE were assayed by measuring the scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical and the inhibition of copper-mediated or cell-mediated LDL oxidation. Production of reactive oxygen species (ROS) and the expression of adhesion molecules were evaluated in HUVECs after exposure to oxLDL and treatment with SLE. Several apoptotic signaling pathways were investigated.


RESULTS
SLE scavenged DPPH and also delayed the kinetics of LDL oxidation in a dose-dependent manner. SLE attenuated the level of oxLDL-induced ROS generation, diminished the expression of endothelial NO synthase (eNOS), and enhanced the expression of adhesion molecules (vascular cellular adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1) and the adherence of monocytic THP-1 cells to HUVECs. OxLDL increased the concentration of intracellular calcium, disturbed the balance of the Bcl-2 protein family, destabilized the mitochondrial membrane potential, increased the amount of cytochrome c released into the cytosol, and increased the activation of caspase 3. These detrimental effects were ameliorated dose-dependently by SLE (P < .05).


CONCLUSIONS
Crude extracts of Solanum lyratum protect against oxLDL-induced injury in endothelial cells by direct antioxidant action.


CONCLUSIONS
Atherosclerosis is a chronic inflammatory disease characterized by lipid-laden lesions within arterialblood vessel walls. Inhibiting the oxidation of low-density lipoprotein may be an effective way to prevent or delay theprogression of atherosclerosis. This study underscores the potential clinical benefits and application of Solanum lyratumextract in controlling oxidized low-density lipoprotein-associated vascular injury and cardiovascular disease.
Kuo
Wei-Wen
WW
Department of Biotechnology, China Medical University, Taichung, Taiwan.
Huang
Chih-Yang
CY
Chung
Jing-Gung
JG
Yang
Shun-Fa
SF
Tsai
Kun-Ling
KL
Chiu
Tsan-Hung
TH
Lee
Shin-Da
SD
Ou
Hsiu-Chung
HC
D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011336:Probability; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity; D032322:Solanum; D014471:Umbilical Veins / Q000166:cytology
D000975:Antioxidants; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein