cyanidin-3-o-beta-glucopyranoside and Disease-Models--Animal

This study investigated the anti-inflammatory effects of cyanidin-3-glucoside (C3G) and blueberry pectin (BP) complexes on mice with dextran sodium sulfate (DSS)-induced colitis before and after high hydrostatic pressure (HHP) treatment. Real-time polymerase chain reaction (RT-PCR), western blotting, and 16S rDNA sequencing were used to study the expression of inflammation-related factors, activation of signal pathway-related proteins, and changes in the intestinal flora in ulcerative colitis (UC) mice. The results showed that HHP-treated C3G-BP complexes significantly relieved diarrhea and blood loss in the stool of UC mice and alleviated colon shortening. The potential mechanism of action involved reduction in intestinal oxidative stress mRNA expression of pro-inflammatory factors, improvement in anti-inflammatory factor levels, inhibition of the NF-κB signaling pathway, increased protein levels of Bcl-2/Bax and caspase-3/cleaved caspase-3 genes, and improved gut microbiota composition. Compared with other experimental groups, the HHP-treated C3G-BP complexes group exhibited the best anti-inflammatory effect on DSS-induced UC mice. The results may provide new ideas for using C3G-BP complexes for treating UC and help develop better processing methods.

Topics: Animals; Anthocyanins; Anti-Inflammatory Agents; Blueberry Plants; Caspase 3; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Hydrostatic Pressure; Mice; Pectins; Sulfates

Black bean seed coat extract (BBSCE) contains a high amount of bioactive compounds which can reduce the risk of cancers, but the underlying mechanism remains poorly understood in vivo. Here using a Drosophila model of a malignant tumor, wherein the activated oncogene Raf (Raf

Topics: Animals; Anthocyanins; Antineoplastic Agents; Autophagy; Disease Models, Animal; Drosophila; MAP Kinase Signaling System; Neoplasms

Topics: Animals; Anthocyanins; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension, Pulmonary; Monocrotaline; p38 Mitogen-Activated Protein Kinases; Pulmonary Artery; Rats; Transforming Growth Factor beta1; Vascular Remodeling

Muscular Dystrophies are severe genetic diseases due to mutations in structural genes, characterized by progressive muscle wasting that compromises patients' mobility and respiratory functions. Literature underlined oxidative stress and inflammation as key drivers of these pathologies. Interestingly among different myofiber classes, type I fibers display a milder dystrophic phenotype showing increased oxidative metabolism. This work shows the benefits of a cyanidin-enriched diet, that promotes muscle fiber-type switch and reduced inflammation in dystrophic alpha-sarcoglyan (Sgca) null mice having, as a net outcome, morphological and functional rescue. Notably, this benefit is achieved also when the diet is administered in dystrophic animals when the signs of the disease are seriously evident. Our work provides compelling evidence that a cyanidin-rich diet strongly delays the progression of muscular dystrophies, paving the way for a combinatorial approach where nutritional-based reduction of muscle inflammation and oxidative stress facilitate the successful perspectives of definitive treatments.

Topics: Animals; Anthocyanins; Dietary Supplements; Disease Models, Animal; Disease Progression; Female; Inflammation Mediators; Male; Mice, Knockout; Mitochondria, Muscle; Muscle, Skeletal; Organelle Biogenesis; Oxidative Stress; Phenotype; Protein Carbonylation; Sarcoglycanopathies; Sarcoglycans

Endothelial cell (EC) dysfunction is a major symptom associated with the initiation of atherosclerosis (AS). Cyanidin-3-O-glucoside (C3G) has the potentials to attenuate AS symptoms. In the current study, the mechanism driving the effects of C3G on AS rabbits and injured ECs were explored by focusing on the changes in miR-204-5p/SIRT1 axis. AS symptoms were induced in rabbits using high-fatty diet (HFD) plus balloon catheter injured method and handled with C3G of two doses. Then the changes in artery wall structure, hemodynamics parameters, blood lipid level, systemic inflammation, and miR-204-5p/SIRT1 axis were detected. EC dysfunction was imitated by subjecting human umbilical vein endothelial cells (HUVECs) to TNF-α, which was then handled with C3G. The changes in apoptosis, inflammation, and miR-204-5p/SIRT1 axis were detected. The results showed that the administrations of C3G improved artery wall structure and hemodynamics parameters, decreased blood lipid levels, and suppressed pro-inflammatory cytokine production in HFD rabbits, which was associated with the down-regulation of miR-204-5p and the up-regulation of SIRT1. In in vitro assays, the treatments of C3G suppressed apoptosis, inhibited inflammation, down-regulated miR-204-5p level, and induced SIRT1 level in HUVECs. The overexpression of miR-204-5p impaired the protective effects of C3G on the injured HUVECs by increasing cell apoptosis and inflammation. The findings outlined in the current study confirmed the protective effects of C3G on EC function, which was associated with the down-regulation of miR-204-5p and the up-regulation of SIRT1.

Topics: Animals; Anthocyanins; Apoptosis; Atherosclerosis; Diet, High-Fat; Disease Models, Animal; Endothelial Cells; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; MicroRNAs; Rabbits; Signal Transduction; Sirtuin 1

Cyanidin-3-O-β-glucoside (Cy-3-g), a typical and abundant monomer of anthocyanins, exhibits a variety of biological activities, such as anti-atherosclerosis, anti-obesity, and anticancer effects. However, to date little is known about its effects on asthma. This study aimed to investigate the efficacy of dietary Cy-3-g on allergic asthma in an animal model. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. The pathological changes of the lung tissues, type 2 helper (Th2)-associated cytokine production in bronchoalveolar lavage fluid (BALF), and the interleukin 4 receptor alpha (IL-4Rα)-signal transducer and activator of transcription 6 (STAT6) signaling pathway activities were assessed. We found that Cy-3-g significantly inhibited OVA-induced inflammatory cell infiltration and mucus hyper-production in lung tissues, reduced the production of interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 13 (IL-13) in BALF. Furthermore, Cy-3-g effectively suppressed OVA-induced up-regulation of the IL-4Rα-STAT6 signaling pathway activity of the lung tissues. These results demonstrated that dietary Cy-3-g could attenuate allergic airway inflammation in a murine asthma model, and Cy-3-g might be used as an agent for asthma prevention and/or treatment in the future.

Topics: Allergens; Animals; Anthocyanins; Anti-Inflammatory Agents; Asthma; Cytokines; Dietary Supplements; Disease Models, Animal; Female; Glucosides; Humans; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Cell Surface; Respiratory Hypersensitivity; STAT6 Transcription Factor; Th2 Cells

In this work, we evaluated the effects of Psidium cattleianum (Red Type) (PcRT) fruit extract on metabolic, behavioral, and neurochemical parameters in rats fed with a highly palatable diet (HPD) consisted of sucrose (65% carbohydrates being 34% from condensed milk, 8% from sucrose and 23% from starch, 25% protein and 10% fat). Animals were divided into 4 groups: standard chow, standard chow + PcRT extract (200 mg/Kg/day by gavage), HPD, HPD + extract. The animals were treated for 150 days. Concerning chemical profiling, LC/PDA/MS/MS analysis revealed cyanidin-3-O-glucoside as the only anthocyanin in the PcRT extract. Our results showed that the animals exposed to HPD presented glucose intolerance, increased weight gain and visceral fat, as well as higher serum levels of glucose, triacylglycerol, total cholesterol, LDL-cholesterol and interleukin-6. These alterations were prevented by PcRT. In addition, HPD caused an increase in immobility time in a forced swimming test and the fruit extract prevented this alteration, indicating an antidepressant-like effect. PcRT treatment also prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD consumption. Moreover, PcRT extract was able to restore Ca

Topics: Animals; Anthocyanins; Antidepressive Agents; Antioxidants; Behavior, Animal; Brazil; Catalase; Corpus Striatum; Diet, Carbohydrate Loading; Disease Models, Animal; Glucose Intolerance; Glucosides; Hippocampus; Hypoglycemic Agents; Hypolipidemic Agents; Metabolic Syndrome; Neuroprotective Agents; Oxidative Stress; Plant Extracts; Psidium; Rats; Rats, Wistar; Tandem Mass Spectrometry; Weight Gain

Cyanidin-3-O-β-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT.. Male C57BL/6 J mice were fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks. In in vitro experiments, the differentiated brown adipocytes (BAC) and C3H10T1/2 clone8 cells were treated with 0.2 mM palmitate with or without Cy-3-G for 72 or 96 h. Then the culture media of C3H10T1/2 clone8 cells were collected for measuring the adipokines secretion by immunoblot assay and were applied to culture HepG2 cells or LO2 cells for 24 h. Lipid accumulation in HepG2 cells or LO2 cells were evaluated by oil red O staining.. Here we found that Cy-3-G regulated the activation of BAT and the expression of adipokines in BAT which were disrupted by HFC diet and alleviated diet induced fatty liver in mice. In in vitro experiments, Cy-3-G inhibited the release of adipokines including extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and fibroblast growth factor 21 (FGF21) from differentiated C3H10T1/2 clone8 cells induced by palmitate, which was accompanied by a reduction of lipid accumulation in HepG2 cells and LO2 cells cultured by the corresponding collected media of C3H10T1/2 clone8 cells.. These results indicate that Cy-3-G can regulate the thermogenic and secretory functions of BAT. Furthermore, our data suggest that the protective effect of Cy-3-G on hepatic lipid accumulation is probably via regulating the secretion of adipokines from BAT.

Topics: Adipocytes; Adipokines; Adipose Tissue, Brown; Animals; Anthocyanins; Cell Differentiation; Diet, High-Fat; Disease Models, Animal; Glucosides; Hep G2 Cells; Humans; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Protective Agents

Anthracyclines are effective anticancer drugs that have improved prognosis of hundred thousand cancer patients worldwide and are currently the most common chemotherapeutic agents used for the treatment of blood, breast, ovarian and lung cancers. However, their use is limited because of a cumulative dose-dependent and irreversible cardiotoxicity that can cause progressive cardiomyopathy and congestive heart failure. Aim of the present study was to determine the cardioprotective activity of a dietary source of cyanidin 3-glucoside (C3G), such as purple corn, against doxorubicin (DOX)-induced cardiotoxicity in mice.. In vitro studies on murine HL-1 cardiomyocytes showed that pretreatment with both pure C3G and purple corn extract improved survival upon DOX treatment. However, C3G and purple corn extract did not affect the cytotoxic effect of DOX on human cancer cell lines. We then validated in vivo the protective role of a C3G-enriched diet against DOX-induced cardiotoxicity by comparing the effect of dietary consumption of corn isogenic lines with high levels of anthocyanins (purple corn - Red diet - RD) or without anthocyanins (yellow corn - Yellow diet - YD) incorporated in standard rodent diets. Results showed that mice fed RD survived longer than mice fed YD upon injection of a toxic amount of DOX. In addition, ultrastructural analysis of hearts from mice fed RD showed reduced histopathological alterations.. Dietary intake of C3G from purple corn protects mice against DOX-induced cardiotoxicity.

Topics: Animal Feed; Animals; Anthocyanins; Cardiotoxicity; Cell Survival; Cytoprotection; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Female; Gene Expression Regulation; Glucosides; Heart Diseases; HeLa Cells; Humans; MCF-7 Cells; Mice, Inbred C57BL; Myocytes, Cardiac; Phytotherapy; Plant Extracts; Plants, Medicinal; Protective Agents; Time Factors; Zea mays

Procyanidins are the oligomeric or polymeric forms of epicatechin and catechin. In this study, we isolated and purified dimer to tetramer procyanidins from black soybean seed coat and investigated the anti-hyperglycemic effects by focusing on glucose transporter 4 (GLUT4) translocation and the underlying molecular mechanism in skeletal muscle of mice. The anti-hyperglycemic effects of procyanidins were also compared with those of monomer (-)-epicatechin (EC) and major anthocyanin, cyanidin-3-O-β-glucoside (C3G). To investigate GLUT4 translocation and its related signaling pathways, ICR mice were orally given procyanidins, EC and C3G in water at 10 μg/kg body weight. The mice were sacrificed 60 min after the dose of polyphenols, and soleus muscle was extracted from the hind legs. The results showed that trimeric and tetrameric procyanidins activated both insulin- and AMPK-signaling pathways to induce GLUT4 translocation in muscle of ICR mice. We confirmed that procyanidins suppressed acute hyperglycemia with an oral glucose tolerance test in a dose-dependent manner. Of these beneficial effects, cinnamtannin A2, one of the tetramers, was the most effective. In conclusion, procyanidins, especially cinnamtannin A2, significantly ameliorate postprandial hyperglycemia at least in part by promoting GLUT4 translocation to the plasma membrane by activating both insulin- and AMPK-signaling pathways.

Topics: AMP-Activated Protein Kinases; Animals; Anthocyanins; Biflavonoids; Catechin; Disease Models, Animal; Glucose; Glucose Transporter Type 4; Glucosides; Humans; Hyperglycemia; Insulin; Mice; Muscle, Skeletal; Proanthocyanidins; Signal Transduction

Oxidative stress (OS) promotes bone loss after menopause, and there is evidence that dietary antioxidants may reduce the level of OS in vivo. This study examined dose-dependent effects of blackberries (BBs) containing mainly cyanidin 3-O-β-d-glucoside (C3G) in preventing bone loss in an ovariectomized (Ovx) rat model. Nine-month-old female (N=38) Sprague-Dawley rats were scanned using dual-energy X-ray absorptiometry for baseline whole body, bone mineral content (BMC), and bone mineral density (BMD). One group was sham operated (Sham) and three groups were ovariectomized (Ovx). The groups and corresponding diets were Sham+control diet (n=12), Ovx+control diet (n=12), Ovx+5% BB (n=7), and Ovx+10% BB (n=7). Control diet was AIN-93M rodent diet, and the Ovx+5% BB and Ovx+10% BB were a diet modified to contain powdered, freeze-dried BB at levels of 5% and 10% (w/w). Following 100 days of treatment, whole body BMC and BMD were reassessed and bone specimens, blood, and 24-h urine samples were collected for analyses. Findings indicate that ovariectomy (Ovx) compromised whole body BMC and trabecular microarchitecture of the proximal tibia and fourth lumbar vertebra. C3G-rich BB at the level of 5% modestly protected BMDs, loss of the tibia, lumbar vertebra, and femur by 2.4%, 2.7%, and 4.3% (P<.0013; .0437; .0004), respectively. BB 5% treatment significantly prevented loss of tibial trabecular bone volume and trabecular number by 37% and 21%, respectively (P<.05), and also significantly prevented tibial trabecular separation by 22%. We conclude that C3G-rich BB treatment at the level of 5% (w/w) but not at 10% (w/w) may modestly reduce Ovx-induced bone loss evident by improved tibial, vertebral, and femoral BMD values, and tibial bone microstructural parameters. Bone protective effects may be as a result of the synergistic effects of phenolic compounds; however, further work is required to determine BBs' specific mechanisms of action.

Topics: Animals; Anthocyanins; Bone and Bones; Bone Density; Bone Density Conservation Agents; Diet; Disease Models, Animal; Female; Femur; Fruit; Glucosides; Humans; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Ovariectomy; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; Rubus; Tibia

Serum high-density lipoprotein-cholesterol (HDL-C) is a risk factor considered to be protective of atherosclerosis. However, atherosclerosis is an inflammatory disease and contributes to impairment in high-density lipoprotein (HDL) function, including reductions in HDL-C, HDL antioxidant and anti-inflammatory activities. Anthocyanins are polyphenols that have demonstrated antioxidant and anti-inflammatory properties. The objective of this study was to determine whether an anthocyanin-rich black elderberry extract (Sambucus nigra) (BEE) (13% anthocyanins) would protect against inflammation-related impairments in HDL function and atherosclerosis in apoE(-/-) mice, a mouse model of hyperlipidemia and HDL dysfunction. We fed an AIN-93M diet supplemented with 1.25% (w/w) BEE or control diet to 10 week old male apoE(-/-) mice for 6 weeks. The BEE fed to mice was rich in cyanidin 3-sambubioside (∼ 9.8% w/w) and cyanidin 3-glucoside (∼ 3.8% w/w). After 6 weeks, serum lipids did not differ significantly between groups, while aspartate transaminase (AST) and fasting glucose were reduced in BEE-fed mice. Hepatic and intestinal mRNA changes with BEE-feeding were consistent with an improvement in HDL function (Apoa1, Pon1, Saa1, Lcat, Clu) and a reduction in hepatic cholesterol levels (increased Ldlr and Hmgcr, reduced Cyp7a1). In BEE-fed mice, serum paraoxonase-1 (PON1) arylesterase activity was significantly higher. In addition, mice fed BEE had significantly lower serum chemokine (C-C motif) ligand 2 (CCL2) compared to control-fed mice. Notably, we observed significant reductions in total cholesterol content of the aorta of BEE-fed mice, indicating less atherosclerosis progression. This study suggests that black elderberry may have the potential to influence HDL dysfunction associated with chronic inflammation by impacting hepatic gene expression.

Topics: Alanine Transaminase; Animals; Anthocyanins; Apolipoprotein A-I; Apolipoproteins B; Aryldialkylphosphatase; Aspartate Aminotransferases; Biomarkers; Blood Glucose; Body Weight; Chemokine CCL2; Cholesterol, HDL; Chromatography, High Pressure Liquid; Disaccharides; Disease Models, Animal; Glucosides; Hyperlipidemias; Intestinal Mucosa; Intestines; Male; Mice; Mice, Knockout; Plant Extracts; Sambucus nigra; Thiobarbituric Acid Reactive Substances; Triglycerides

This study investigated whether cyanidin-3-O-β-glucoside (Cy-3-G), a predominant anthocyanin, could exert a protective role on liver injury and its further mechanisms of the anti-fibrosis actions in mice. The results demonstrated that the treatment of Cy-3-G (800 mg/kg diet) for 8 weeks significantly attenuated hepatotoxicity and fibrosis in carbon tetrachloride (CCl4) administered mice. Cy-3-G strongly down-regulated the expression of α-smooth muscle actin (α-SMA), desmin, and matrix metalloproteinase (MMPs), which showed its suppression effect on the activation of hepatic stellate cells (HSCs). In addition, Cy-3-G favorably regulated oxidative stress and apoptosis in liver. Furthermore, Cy-3-G ameliorated the infiltration of inflammatory cells such as neutrophils and leukocytes and meanwhile suppressed the production of pro-inflammatory cytokines and growth factors. In conclusion, daily intake of Cy-3-G could prevent liver fibrosis progression in mice induced by CCl4 through inhibiting HSC activation, which provides a basis for clinical practice of liver fibrosis prevention.

Topics: Animals; Anthocyanins; Carbon Tetrachloride; Cytokines; Disease Models, Animal; Glucosides; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Oryza; Oxidative Stress; Plant Extracts; Protective Agents

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

To investigate the effect of cyanidin-3-O-glucoside (C3G) on a rat retinal degeneration (RD) model.. Experimental RD was induced in rats by the intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg. C3G extracted from mulberry (Morus alba L.) fruit (50 mg/kg) was orally administered, daily for 1, 2 and 4 weeks after MNU injection. The effects of C3G administration on MNU-induced RD retinas were histologically and functionally assessed by hematoxylin and eosin staining and electroretinography (ERG), respectively. The degree of retinal injury in C3G-administered RD rats was evaluated by immunohistochemistry with an antibody against glial fibrillary acidic protein (GFAP). The preferential protective effect of C3G on scotopic vision was examined by western blot analysis.. Marked loss of photoreceptors in the outer nuclear layer (ONL) was observed in RD rats at 2 and 4 weeks after MNU injection, while the ONL in the MNU-induced RD rats given C3G was relatively well preserved. Immunohistochemistry with anti-GFAP showed that retinal injury was also reduced in the retinas of the rats given C3G. Functional assessment by using ERG recordings showed that scotopic ERG responses were significantly increased in RD rats given C3G for 4 weeks (p < 0.01) compared with that of untreated RD rats. In the RD rats given short-term C3G (for 1 and 2 weeks), the increase in ERG responses was not significant. In addition, western blot analysis showed that rhodopsin level in the C3G-administered RD retinas significantly increased compared to that in the non-administered RD retinas (p < 0.05), whereas red/green opsin level did not show any significant difference.. Long-term administration of C3G extracted from mulberry fruit could structurally reduce photoreceptor damage and functionally improve scotopic visual functions in the RD rat model induced by MNU.

Topics: Alkylating Agents; Animals; Anthocyanins; Apoptosis; Disease Models, Animal; Electroretinography; Glucosides; Male; Methylnitrosourea; Morus; Night Vision; Photoreceptor Cells, Vertebrate; Plant Extracts; Rats; Rats, Sprague-Dawley; Retinal Degeneration

Cyanidin-3-O-β-glucoside (C3G) (CAS number 7084-24-4), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. However, the effect of C3G on lipopolysaccharide (LPS)-induced mastitis and the molecular mechanisms have not been investigated. In this study, we detected the protective effects of C3G on a LPS-induced mouse mastitis model and investigated the molecular mechanisms in LPS-stimulated mouse mammary epithelial cells (MMECs). Our results showed that C3G could attenuate mammary histopathologic changes and myeloperoxidase activity, and inhibit TNF-α, interleukin (IL)-1β, and IL-6 production caused by LPS. Meanwhile, C3G dose-dependently inhibited TNF-α and IL-6 in LPS-stimulated MMECs. C3G suppressed LPS-induced nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) activation. Furthermore, C3G disrupted the formation of lipid rafts by depleting cholesterol. Moreover, C3G activated liver X receptor (LXR)-ABCG1-dependent cholesterol efflux. Knockdown of LXRα abrogated the anti-inflammatory effects of C3G. In conclusion, C3G has a protective effect on LPS-induced mastitis. The promising anti-inflammatory mechanisms of C3G are associated with upregulation of the LXRα-ABCG1 pathway which result in disrupting lipid rafts by depleting cholesterol, thereby suppressing toll-like receptor 4-mediated NF-κB and IRF3 signaling pathways induced by LPS.

Topics: Animals; Anthocyanins; Cytokines; Disease Models, Animal; Female; Glucosides; Humans; Lipopolysaccharides; Mammary Glands, Animal; Mastitis; Mice

Ethanol exposure induces neurodegeneration in the developing central nervous system (CNS). Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during pregnancy and are the most common nonhereditary cause of mental retardation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Multiple mechanisms have been proposed for ethanol-induced neurodegeneration, and oxidative stress is one of the most important mechanisms. Recent evidence indicates that glycogen synthase kinase 3β (GSK3β) is a potential mediator of ethanol-mediated neuronal death. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. Our previous study suggested that C3G inhibited GSK3β activity in neurons. Using a third trimester equivalent mouse model of ethanol exposure, we tested the hypothesis that C3G can ameliorate ethanol-induced neuronal death in the developing brain. Intraperitoneal injection of C3G reduced ethanol-meditated caspase-3 activation, neurodegeneration, and microglial activation in the cerebral cortex of 7-day-old mice. C3G blocked ethanol-mediated GSK3β activation by inducing phosphorylation at serine 9 while reducing the phosphorylation at tyrosine 216. C3G also inhibited ethanol-stimulated expression of malondialdehyde (MDA) and p47phox, indicating that C3G alleviated ethanol-induced oxidative stress. These results provide important insight into the therapeutic potential of C3G.

Topics: Alcohol-Induced Disorders, Nervous System; Animals; Anthocyanins; Brain; Disease Models, Animal; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Glucosides; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Pregnancy

Topics: Anesthetics; Animals; Anthocyanins; Antioxidants; Carbon Monoxide; Curcumin; Cytoprotection; Disease Models, Animal; Flavonoids; Glucosides; Heme Oxygenase-1; Hepatocytes; Humans; Isoflurane; Liver; Liver Diseases; Liver Transplantation; Phenols; Polyphenols; Propofol; Reperfusion Injury