cyanidin-3-o-beta-glucopyranoside and Acute-Lung-Injury

Cyanidin-3-O-glucoside (C3G), an anthocyanin belonging to the flavonoid family and commonly present in food and vegetables in human diet, has exhibited anti-inflammatory and anti-oxidant effects. This study aimed to investigate the protective ability of C3G against inflammatory and oxidative injuries, as well as to clarify the possible mechanism in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro and acute respiratory distress syndrome mouse model in vivo. HUVECs or male Kunming mice were pretreated with C3G 1 h before LPS stimulation. C3G significantly inhibited the production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-1β) in cell supernatants and bronchoalveolar lavage fluid (BALF) as determined by enzyme-linked immunosorbent assay. Histopathologic examination with hematoxylin and eosinstaining showed that C3G pretreatment substantially suppressed inflammatory cell infiltration, alveolar wall thickening, and interstitial edemain lung tissues. C3G markedly prevented LPS-induced elevation of malondialdehyde and myeloperoxidase levels in lung tissue homogenates, wet to dry ratio of lung tissues, total cells, and inflammatory cells (neutrophils and macrophages) in BALF. Moreover, C3G reduced superoxide dismutase activity in the lung tissue homogenates. Western blot assay also showed that C3G pretreatment significantly suppressed LPS-induced activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by blocking the phosphorylation of inhibitor κB-α, NF-κB/P65, extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase in the lung tissues. In summary, C3G may ameliorate LPS-induced injury, which results from inflammation and oxidation, by inhibiting NF-κB and MAPK pathways and playing important anti-inflammatory and anti-oxidative roles.

Topics: Acute Lung Injury; Animals; Anthocyanins; Cell Survival; Dose-Response Relationship, Drug; Glucosides; Humans; Lipopolysaccharides; Male; MAP Kinase Signaling System; Mice; NF-kappa B

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.. 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.. 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-1β, 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.. 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.

Topics: Acute Lung Injury; Animals; Anthocyanins; Disease Models, Animal; Drug Evaluation, Preclinical; Glucosides; Lung; Male; NF-kappa B; Oxidative Stress; Random Allocation; Rats, Sprague-Dawley; Sepsis

Cyanidin-3-O-β-glucoside (C3G), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. The aim of this study was to detect the effect of C3G on LPS-induced acute lung injury and to investigate the molecular mechanisms. Acute lung injury was induced by intratracheal administration of LPS in mice. Alveolar macrophages from mice were stimulated with LPS and were treated with C3G. Our results showed that C3G attenuated lung histopathologic changes, myeloperoxidase (MPO) activity, TNF-α, IL-1β and IL-6 production in LPS-induced acute lung injury model. In vitro, C3G dose-dependently inhibited TNF-α, IL-1β, IL-6, IL-10 and IFN-β production, as well as NF-κB and IRF3 activation in LPS-stimulated alveolar macrophages. Furthermore, C3G disrupted the formation of lipid rafts by depleting cholesterol and inhibited TLR4 translocation into lipid rafts. Moreover, C3G activated LXRα-ABCG1-dependent cholesterol efflux. Knockout of LXRα abrogated the anti-inflammatory effects of C3G. In conclusion, C3G has a protective effect on LPS-induced acute lung injury. The promising anti-inflammatory mechanisms of C3G is associated with up-regulation of the LXRα-ABCG1 pathway which result in disrupting lipid rafts by depleting cholesterol and reducing translocation of TLR4 to lipid rafts, thereby suppressing TLR4 mediated inflammatory response.

Topics: Acute Lung Injury; Animals; Anthocyanins; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Biological Transport; Cells, Cultured; Cholesterol; Gene Expression Regulation; Glucosides; Interferon Regulatory Factor-3; Interferon-beta; Interleukin-10; Interleukin-1beta; Interleukin-6; Intubation, Intratracheal; Lipopolysaccharides; Lipoproteins; Liver X Receptors; Macrophages, Alveolar; Male; Membrane Microdomains; Mice; NF-kappa B; Orphan Nuclear Receptors; Peroxidase; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha