Crude extracts of Solanum lyratum protect endothelial cells against oxidized low-density lipoprotein-induced injury by direct antioxidant action

Abstract

[[abstract]]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). Conclusion: Crude extracts of Solanum lyratum protect against oxLDL-induced injury in endothelial cells by direct antioxidant action. (J Vasc Surg 2009;50:849-60.