cyanidin-3-o-beta-glucopyranoside and Inflammation

The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1β, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-β, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.

Topics: Animals; Anthocyanins; Carcinoma, Large Cell; Cell Line, Tumor; Fluorouracil; Glucosides; Inflammation; Lonicera; Lung; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; Phytotherapy; RNA, Messenger; Tumor Microenvironment; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

In this article, we investigated the in vitro potential beneficial effects of the anthocyanin cyanidin-3-O-glucoside (C3G) on inflammation and insulin resistance markers induced by palmitic acid (PA) in human SGBS adipocytes. Results demonstrated that PA reduced insulin sensitivity in SGBS cells with a significant inhibition of Akt phosphorylation, with a higher sensitivity to PA than murine 3T3-L1 adipocytes, GLUT-1 and GLUT-4 glucose transporters and the enzyme hexokinase-II. C3G pretreatment (1-20 μM) reverted these effects. Moreover, we demonstrated, for the first time in human adipocytes, that cells exposure to PA induced gene expression of proinflammatory cytokines TNF-α, IL-6, IL-8, and MCP-1. Cells pretreatment with C3G resulted in a reduction in mRNA levels starting at very low concentrations (1 μM). In conclusion, this study highlights the effects of PA on inflammation and insulin resistance markers in human adipocytes, and confirm the role of C3G in the prevention of lipotoxicity in dysfunctional adipocytes.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Anthocyanins; Cytokines; Dose-Response Relationship, Drug; Humans; Inflammation; Mice; Palmitic Acid

Topics: Animals; Anthocyanins; Cell Line; Cell Movement; Diabetic Retinopathy; Endothelial Cells; Humans; Inflammation; Mice; Mice, Inbred C57BL; Microglia; Neovascularization, Pathologic; RNA, Messenger

Formation of advanced glycation end products (AGEs), which are associated with diabetes mellitus, contributes to prominent features of osteoarthritis, i.e., inflammation-mediated destruction of articular cartilage. Among the phytochemicals which play a role in anti-inflammatory effects, anthocyanins have also been demonstrated to have anti-diabetic properties. Purple corn is a source of three major anthocyanins: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside. Purple corn anthocyanins have been demonstrated to be involved in the reduction of diabetes-associated inflammation, suggesting that they may have a beneficial effect on diabetes-mediated inflammation of cartilage. This investigation of the chondroprotective effects of purple corn extract on cartilage degradation found a reduction in glycosaminoglycans released from AGEs induced cartilage explants, corresponding with diminishing of uronic acid loss of the cartilage matrix. Investigation of the molecular mechanisms in human articular chondrocytes showed the anti-inflammatory effect of purple corn anthocyanins and the metabolite, protocatechuic acid (PCA) on AGEs induced human articular chondrocytes via inactivation of the NFκb and MAPK signaling pathways. This finding suggests that purple corn anthocyanins and PCA may help ameliorate AGEs mediated inflammation and diabetes-mediated cartilage degradation.

Topics: Anthocyanins; Cartilage; Cell Line; Chondrocytes; Diabetes Complications; Diabetes Mellitus; Glucosides; Glycation End Products, Advanced; Glycosaminoglycans; Humans; Hydroxybenzoates; Inflammation; MAP Kinase Signaling System; NF-kappa B; Osteoarthritis; Zea mays

Our previous research showed the antioxidant activity of anthocyanins extracted from. Acute renal injury model was initiated by 30 min clamping bilateral renal pedicle and followed by 24-hour reperfusion in C57Bl/6J mice. Four groups of mice were orally pretreated in 50 mg/g/12 h for two weeks with cyanidin-3-arabinoside, cyanidin-3-glucodise, and cyaniding-3-galactoside and anthocyanins (three-cyanidin mixture), respectively, sham-control group and the renal injury-untreated groups only with saline.. The model resulted in renal dysfunction with high serum creatinine, blood urea nitrogen, and changes in proinflammatory cytokines (TNF-ɑ, IL-1. the current study provided the first attempt to investigate the role of anthocyanins purified from

Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Arabinonucleosides; Body Weight; Caspase 9; Fruit; Galactosides; Inflammation; Kidney; Kidney Failure, Chronic; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Oxidative Stress; Photinia; Reperfusion; Reperfusion Injury; Risk

The bacterial keratitis causes viability loss and apoptosis in the corneal epithelial cells (CECs). The cyanidin-3-O-glucoside (C3G) benefits visual system and also possess anti-bacterial and anti-inflammatory potentials. In the current study, the effects of C3G on human CECs (HCECs) against bacterial lipopolysaccharide (LPS)-induced disorders were assessed, and the mechanism driving the protective effect was explored by focusing on let-7b-5p-mediated HMGA2/PI3K/Akt pathway. The HCECs were incubated LPS of P. aeruginosa to induce inflammation and apoptosis, and then treated with C3G. The changes in cell viability, apoptosis, and inflammation were detected. Moreover, the effects of LPS and C3G on let-7b-5p level and HMGA2/PI3K/Akt pathway activity were also assessed. Thereafter, the HCECs were further transfected with let-7b-5p inhibitor to confirm its role in the vision-protective effects of C3G. The interaction between let-7b-5p and HMGA2 was verified with dual luciferase assay. The LPS treatment suppressed viability and induced apoptosis and inflammation in HCECs, which was associated with the down-regulated let-7b-5p level and up-regulated HMGA2/PI3K/Akt pathway activity. The impairments of LPS on HCECs were attenuated by C3G: the compound increased cell viability and inhibited apoptosis and inflammation. The C3G also induced let-7b-5p level and inactivated HMGA2/PI3K/Akt pathway. However, after the inhibition of let-7b-5p, the protective effects of C3G on HCECs against LPS were blocked. The results of dual luciferase assay showed the direct binding let-7b-5p to the promoter of HMGA2 gene. It was inferred that the C3G could ameliorate the LPS-induced disorders in HCECs. The effect depended on the induced level of let-7b-5p, which then inhibited HMGA2/PI3K/Akt pathway.

Topics: Anthocyanins; Cell Survival; Cells, Cultured; Cornea; Epithelial Cells; HMGA2 Protein; Humans; Inflammation; Lipopolysaccharides; MicroRNAs; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

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

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Anthocyanins; Fatty Acid-Binding Proteins; Glucose Transporter Type 1; Glucosides; Humans; Inflammation; Insulin Resistance; Mice; NF-kappa B; Palmitic Acid; PPAR gamma; Signal Transduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint tissue inflammation. Cyanidin-3-glucoside (C3G) is a major component in the flavonoid family and has shown anti-inflammatory, anti-oxidant and anti-tumour activity. In this study, we investigated the effects of C3G on lipopolysaccharides (LPS)-induced inflammation on human rheumatoid fibroblast-like synoviocytes (FLS) and on collagen-induced arthritis (CIA) mice model. We treated FLS with C3G followed by LPS induction, the expressions of tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway were analyzed. CIA was induced in mice and the arthritic mice were treated with C3G for 3 weeks. The disease severity was compared between control and C3G treated mice. The serum levels of TNF-α, IL-1β and IL-6 were analyzed by ELISA. C3G inhibited LPS-induced TNF-α, IL-1β and IL-6 expression in FLS. Moreover, C3G inhibited LPS-induced p65 production and IκBa, p38, ERK and JNK phosphorylation. Administration of C3G significantly attenuated disease in mice with CIA and decreased the serum level of TNF-α, IL-1β and IL-6. C3G inhibited LPS-induced inflammation in human FLS by inhibiting activation of NF-κB and MAPK signalling pathway. C3G exhibited therapeutic effects in mice with CIA.

Topics: Animals; Anthocyanins; Arthritis, Experimental; Cell Survival; Collagen; Cytokines; Enzyme Activation; Fibroblasts; Glucosides; Humans; Inflammation; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Synoviocytes

Diabetic nephropathy (DN) is a common complication of diabetes and the major cause of chronic kidney disease. Cyanidin 3-glucoside (C3G) is the most widespread anthocyanin in nature. In the present study, we aimed to investigate the possible effects of C3G on DN in db/db mice. We found that body weights and high levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure in diabetic mice were significantly reduced by C3G. C3G also reduced the ratio of kidney to body weight and the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological changes of kidneys, reduced the surface area of Bowman's capsule, glomerular tuft, Bowman's space, and decreased renal expression of collagen IV, fibronectin, transforming growth factor β 1 (TGFβ1), matrix metalloprotein 9 (MMP9) and α-smooth muscle actin (α-SMA) in db/db mice. The Lee's index, perirenal white adipose tissue weight, and high levels of blood and renal triglyceride and cholesterol were decreased by C3G. Moreover, C3G reduced systemic levels and renal expression of tumor necrosis factor ɑ (TNFɑ), IL-1ɑ, and monocyte chemotactic protein-1 (MCP-1), indicating the inhibition of inflammation. Furthermore, C3G increased glutathione (GSH) level and decreased GSSG level in kidneys of diabetic mice. The renal mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) was increased by C3G in diabetic mice. Buthionine sulphoximine (BSO), an inhibitor of GSH synthesis, inhibited the effects of C3G on glucose metabolic dysfunction and DN. The data demonstrates that enhancement of GSH pool is involved in the renal-protective effects of C3G. Overall, C3G could be a promising therapeutic option for attenuation of diabetes and DN.

Topics: Animals; Anthocyanins; Buthionine Sulfoximine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Fibrosis; Glucose; Glucosides; Glutathione; Inflammation; Kidney; Lipid Metabolism; Male; Mice, Inbred C57BL; Obesity; Protective Agents

Higher dietary intakes of anthocyanins have been linked epidemiologically to decreased risk for metabolic syndrome, type 2 diabetes and cardiovascular events; clinical trials and rodent studies evaluating ingestion of anthocyanin-rich extracts confirm favorable effects of these agents on endothelial function and metabolic syndrome. However, these benefits of anthocyanins are lost in rats whose gut microbiome has been eliminated with antibiotic treatment - pointing to bacterial metabolites of anthocyanins as the likely protective agents. A human pharmacokinetic assessment of orally administered cyanidin-3-O-glucoside, a prominent anthocyanin, has revealed that, whereas this compound is minimally absorbed, ferulic acid (FA) is one of its primary metabolites that appears in plasma. FA is a strong antioxidant and phase 2 inducer that has exerted marked anti-inflammatory effects in a number of rodent and cell culture studies; in particular, FA is highly protective in rodent models of diet-induced weight gain and metabolic syndrome. FA, a precursor for lignan synthesis, is widely distributed in plant-based whole foods, mostly in conjugated form; whole grains are a notable source. Coffee ingestion boosts plasma FA owing to gastrointestinal metabolism of chlorogenic acid. Hence, it is reasonable to suspect that FA mediates some of the broad health benefits that have been associated epidemiologically with frequent consumption of whole grains, anthocyanins, coffee, and unrefined plant-based foods. The molecular basis of the anti-inflammatory effects of FA may have been clarified by a recent study demonstrating that FA can target the adaptor protein MyD88; this plays an essential role in pro-inflammatory signaling by most toll-like receptors and interleukin-1β. If feasible oral intakes of FA can indeed down-regulate MyD88-dependent signaling, favorable effects of FA on neurodegeneration, hypothalamic inflammation, weight gain, adipocyte and beta cell function, adiponectin secretion, vascular health, and cartilage and bone integrity can be predicted. Since FA is well tolerated, safe, and natural, it may have great potential as a protective nutraceutical, and clinical trials evaluating its effects are needed.

Topics: Adiponectin; Administration, Oral; Animals; Anthocyanins; Anti-Inflammatory Agents; Antioxidants; Coffee; Coumaric Acids; Diabetes Mellitus; Gastrointestinal Microbiome; Glucosides; Glutathione; Humans; Inflammation; Myeloid Differentiation Factor 88; Osteoclasts; Oxidative Stress; Rats; Signal Transduction; Whole Grains

We assessed phytochemical components of anthocyanins from purple sweet potato (PSP) and purple potato (PP) with UPLC-MS/MS, and investigated their inhibitory effect on inflammatory response in alcoholic liver disease (ALD). Results showed that serum AST and ALT levels in PP anthocyanins (PPAs) and PSP anthocyanins (PSPAs) treatments were lower than those of alcohol-treated group. PPAs and PSPAs could inhibit mRNA expressions of inflammatory factors (TNF-α, VCAM-1, IFN-γ and CXCL-1). The mRNA levels of NF-κB, STAT, and TLR in PPAs and PSPAs treatment groups were lower than in alcohol treatment group. Our results indicate that PP and PSP are good source of anti-inflammatory anthocyanins to prevent ALD.

Topics: Animals; Anthocyanins; Anti-Inflammatory Agents; Chemokine CXCL1; Ethanol; Female; Glucosides; Inflammation; Interferon-gamma; Ipomoea batatas; Liver Diseases, Alcoholic; Liver Function Tests; Male; Mice; NF-kappa B; Plant Extracts; STAT3 Transcription Factor; Tandem Mass Spectrometry; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.

Topics: Animals; Anthocyanins; Blueberry Plants; Glucosides; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; NF-E2-Related Factor 2; NF-kappa B; Protein Transport; Ribes; Rubus; Tumor Necrosis Factor-alpha

Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2'-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways.

Topics: Animals; Anthocyanins; Dose-Response Relationship, Drug; Female; Glucosides; Inflammation; Mice; Mice, Hairless; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; Random Allocation; Signal Transduction; Skin Absorption; Ultraviolet Rays

Berries are an excellent source of dietary flavonoids which have several health benefits.. We evaluated well-characterized anthocyanins (ANCs) and proanthocyanidins (PACs) from fermented blueberry-blackberry beverages. Wines were produced from highbush blueberries and blackberries grown in Illinois and blended to create ratios ranging from 100% blueberry to 100% blackberry. Total ANCs of the wine were strongly correlated to total phenolics (r = 0.99, p < 0.05) and to antioxidant capacity (r = 0.77, p < 0.05). ANC- and PAC-enriched fractions were purified from each wine blend and a phenolic profile was generated. ANCs increased with more blackberries from 1114 to 1550 mg cyanidin-3-O-glucoside (C3G) equivalents/L. Hydrolysable tannins were identified in the PAC-enriched fraction. Both ANC- and PAC-enriched fractions inhibited starch-degrading enzyme α-glucosidase and dipeptidyl peptidase-IV activity. Computational docking demonstrated that delphinidin-3-arabinoside effectively inactivated dipeptidyl peptidase-IV by binding with the lowest interaction energy (-3228 kcal/mol). ANC and PAC (100 μM C3G and epicatechin equivalents, respectively) from blueberry-blackberry blends reduced LPS-induced inflammatory response in mouse macrophages via the nuclear factor kappa B-mediated pathway.. ANC- and PAC- (including hydrolysable tannins in blackberry) enriched fractions from blueberry and blackberry fermented beverages are beneficial sources of antioxidants, inhibitors of carbohydrate-utilizing enzymes, and potential inhibitors of inflammation.

Topics: alpha-Amylases; alpha-Glucosidases; Animals; Anthocyanins; Antioxidants; Beverages; Blueberry Plants; Cell Line, Tumor; Cell Proliferation; Fermentation; Fruit; Glucosides; Inflammation; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Plant Extracts; Polyphenols; Proanthocyanidins; Wine

The potential use of polyphenols in the prevention and treatment of chronic inflammatory diseases has been extensively investigated although the mechanisms involved in cellular signaling need to be further elucidated. Cyanidin-3-glucoside is a typical anthocyanin of many pigmented fruits and vegetables widespread in the human diet. In the present study, the protection afforded by cyanidin-3-glucoside against cytokine-triggered inflammatory response was evaluated in the human intestinal HT-29 cell line, in comparison with 5-aminosalicylic acid, a well-established anti-inflammatory drug, used in inflammatory bowel disease. For this purpose, some key inflammatory mediators and inflammatory enzymes were examined. Our data showed that cyanidin-3-glucoside reduced cytokine-induced inflammation in intestinal cells, in terms of NO, PGE2 and IL-8 production and of iNOS and COX-2 expressions, at a much lower concentration than 5-aminosalicylic acid, suggesting a higher anti-inflammatory efficiency. Interestingly, cyanidin-3-glucoside and 5-aminosalicylic acid neither prevented IkB-α degradation nor the activation of NF-kB, but significantly reduced cytokine-induced levels of activated STAT1 accumulated in the cell nucleus. In addition, we established that phosphorylated p38 MAPK was not involved in the protective effect of cyanidin-3-glucoside or 5-aminosalicylic acid. Taking into account the high concentrations of dietary anthocyanins potentially reached in the gastrointestinal tract, cyanidin-3-glucoside may be envisaged as a promising nutraceutical giving complementary benefits in the context of inflammatory bowel disease.

Topics: Anthocyanins; Anti-Inflammatory Agents; Cell Line; Cell Nucleus; Cell Survival; Cyclooxygenase 2; Cytokines; Dinoprostone; Enzyme Activation; Glucosides; HT29 Cells; Humans; Inflammation; Inflammation Mediators; Inflammatory Bowel Diseases; Interleukin-8; Intestinal Mucosa; Mesalamine; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Phosphorylation; STAT1 Transcription Factor; Transcription Factor RelA

Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive protein (CRP). Both atorvastatin calcium (lipitor) as well as flavonoid rich fruit such as tart cherry demonstrate potent anti-inflammatory effects on IL-6 secretion. In this study, we investigated whether tart cherry extract or specific anthocyanins contained in the tart cherry show synergistic anti-inflammatory effects with lipitor. Results showed that LPS-induced adipose stem cell secretion of IL-6 reduced with the addition of tart cherry extract, a mixture of tart cherry anthocyanins, and pure tart cherry cyanidin-3-O-glucoside (C3G) in a dose-dependent manner. Furthermore, lipitor and C3G exhibited synergistic effects in reducing LPS-induced IL-6 secretion from adipose stem cells. In conclusion, these results support potential benefits of using dietary phytochemicals in conjunction with pharmacological therapies to decrease adipose inflammation, drug doses, and ultimately, drug-induced adverse effects.

Topics: Adipose Tissue; Anthocyanins; Anti-Inflammatory Agents; Atorvastatin; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Fruit; Glucosides; Heptanoic Acids; Herb-Drug Interactions; Humans; Inflammation; Interleukin-6; Lipopolysaccharides; Phytotherapy; Plant Extracts; Prunus; Pyrroles; Stem Cells

Anthocyanins are a group of naturally occuring phenolic compounds related to the coloring of plants, flowers and fruits. These pigments are important as quality indicators, as chemotaxonomic markers and for their antioxidant activities. Here, we have investigated the therapeutic efficacy of anthocyanins contained in blackberry extract (cyanidin-3-O-glucoside represents about 80% of the total anthocyanin contents) in an experimental model of lung inflammation induced by carrageenan in rats. Injection of carrageenan into the pleural cavity elicited an acute inflammatory response characterized by fluid accumulation which contained a large number of neutrophils as well as an infiltration of polymorphonuclear leukocytes in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx) and prostaglandin E2 (PGE2). All parameters of inflammation were attenuated in a dose-dependent manner by anthocyanins (10, 30 mg kg(-1) 30 min before carrageenan). Furthermore, carrageenan induced an upregulation of the adhesion molecule ICAM-1, nitrotyrosine and poly (ADP-ribose) synthetase (PARS) as determined by immunohistochemical analysis of lung tissues. The degree of staining was lowered by anthocyanins treatment. Thus, the anthocyanins contained in the blackberry extract exert multiple protective effects in carrageenan-induced pleurisy.

Topics: Acute Disease; Animals; Anthocyanins; Carrageenan; Dinoprostone; Exudates and Transudates; Fruit; Glucosides; Immunohistochemistry; Inflammation; Intercellular Adhesion Molecule-1; Lipid Peroxidation; Lung; Male; Malondialdehyde; Neutrophils; Nitrates; Nitrites; Peroxidase; Plant Extracts; Pleurisy; Poly(ADP-ribose) Polymerases; Rats; Rats, Sprague-Dawley; Time Factors; Tyrosine

Anthocyanins are used for food color, and they are widely distributed in the human diets, suggesting that we ingest considerable amounts of anthocyanins from plant-based daily diets. We have demonstrated that a typical anthocyanin, cyanidin 3-O-beta-D-glucoside (C3G), suppressed the zymosan-induced inflammatory response in rats when it was orally administered. The elevation of the peritoneal exudate NOx, tumor necrosis factor (TNF) alpha interleukin-1beta (IL-1beta), IL-6, and the cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentrations were significantly suppressed by the administration of C3G. The zymosan treatment resulted in an increase in the serum alpha2-macroglobulin and decreases in the serum albumin and transferrin levels, which are recognized as acute phase proteins. However, these levels were normalized by the administration of C3G. The inducible nitric oxide synthase (iNOS) protein level in the peritoneal exudate cells was markedly elevated in the control group treated with zymosan. However, the administration of C3G significantly reduced the level of iNOS in the peritoneal exudate cells. Taken altogether, our findings provide a biochemical basis for the use of C3G as a functional food factor and can also have important implications for the prevention of the NO-mediated inflammatory diseases.

Topics: Acute-Phase Proteins; Administration, Oral; Animals; Anthocyanins; Antioxidants; Chemokine CXCL1; Chemokines; Chemokines, CXC; Chemotactic Factors; Glucosides; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-6; Liver; Male; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Zymosan