Resveratrol protects vascular smooth muscle cells against high glucose-induced oxidative stress and cell proliferation in vitro.

BACKGROUND: Resveratrol exhibits beneficial effects against numerous degenerative diseases at different stages of pathogenesis. This study investigated potential mechanisms and resveratrol effects on high glucose (HG)-induced oxidative stress (30 mM D-glucose, 30 min) and cell proliferation (30 mM D-glucose, 24 h) in vascular smooth muscle cells (VSMCs).

MATERIAL/METHODS: Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Total antioxidant capacity (TAC), malonyldialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. VSMC proliferation was measured by CCK-8 assays and through propidium iodide-based cell cycle analysis. Expression of NAD(P)H oxidase, proliferation proteins, and cell signalling were assessed by immunoblot analysis.

RESULTS: Co-treatment of primary cultures of VSMCs with 1-100 μM resveratrol decreased HG-induced ROS overproduction (P<0.05). Resveratrol also abolished HG-induced phosphorylation of oxidase subunit p47 phox and reduced HG-induced cyclin D1, cyclin E, and PCNA expression in a concentration-dependent manner. Furthermore, resveratrol (10 μM) attenuated HG-induced phosphorylation of Akt, p38 mitogen-activated protein kinase (MAPK), ERK 1/2, and JNK1/2 without affecting total levels. HG stimulation enhanced downstream IκB-α phosphorylation and NF-κB activity, and resveratrol repressed these effects.

CONCLUSIONS: Resveratrol inhibits HG-induced oxidative stress and VSMC proliferation by suppressing ROS generation, NADPH oxidase, Akt phosphorylation, p38 MAPK/JNK/ERK phosphorylation, and IκB-α and NF-κB activities.