Cyanidin-3-O-glucoside Induces Apoptosis and Inhibits Migration of Tumor Necrosis Factor-α-Treated Rat Aortic Smooth Muscle Cells.

Blueberries are rich in anthocyanins (ACNs), which have recently been noted to protect against atherosclerosis development in mice. Cyanidin-3-O-glucoside (C3G), a member of blueberry ACN family, can inhibit the tumor necrosis factor-α (TNF-α)-induced proliferation of vascular smooth muscle cells (VSMCs). However, the effects of C3G on VSMC apoptosis and migration remain unclear. This study was thus conducted to examine whether and how C3G affected the apoptosis and migration of rat aortic smooth muscle cells (RASMCs) challenged by TNF-α. Primary cultured RASMCs were pretreated with C3G (25, 50 or 100 µM) for 2 h and then stimulated with TNF-α (10 ng/ml) for additional 24 h. Our results illustrated that C3G pretreatment induced significant apoptosis in TNF-α-stimulated RASMCs in a dose-dependent way, which was accompanied with increased cleaved caspase-3, caspase-9 and Bax and decreased Bcl-2. Moreover, RASMC migration was enhanced by TNF-α, but markedly suppressed by C3G pretreatment. The expressions and activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 were inhibited by C3G. In addition, TNF-α-enhanced nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65 and phosphorylation of NF-κB inhibitor α (IκBα) in RASMCs were attenuated by C3G. In summary, our study reveals that C3G can induce significant apoptosis in TNF-α-treated RASMCs and markedly inhibit their migration.

Cyanidin-3-O-glucoside attenuates acute lung injury in sepsis rats.

BACKGROUND: Sepsis is a complex syndrome with high mortality, which often induces acute lung injury (ALI) and acute respiratory distress syndrome. Cyanidin-3-O-glucoside (C3G), the most active anthocyanin in the blueberry extracts, has been demonstrated to have pulmonary protective effects in some ALI models. This study aims to evaluate the potential protective effect of C3G on sepsis-evoked ALI in rats. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats to establish sepsis-induced ALI model. Rats were injected intraperitoneally with 10 or 30 mg/kg of C3G after CLP and then the survival was recorded every 12 h for 96 h. The pulmonary protective effects of C3G on CLP-induced ALI were evaluated at 24 h after CLP. RESULTS: The results demonstrated that C3G treatment significantly improved the survival rate of CLP rats and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and myeloperoxidase activity. In addition, C3G markedly decreased malondialdehyde content and increased superoxide dismutase activity and glutathione level. Serum levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were also decreased by C3G administration, as well as protein expression of cyclooxygenase-2 and production of prostaglandin E2 in the lung. Furthermore, C3G treatment upregulated protein expression of inhibitors of NF-κBα and downregulated expressions of nuclear factor kappa-B (NF-κB) p65 and p-p65 in the lung, thereby inhibiting the NF-κB-DNA binding activity. CONCLUSIONS: These findings indicate that C3G exerts pulmonary protective effects on CLP-induced ALI rats. The effect may be associated with NF-κB signaling pathway suppression.