PMID: 

Ear Nose Throat J. 2019 Sep 26:145561319866826. Epub 2019 Sep 26. PMID: 31558064

Abstract Title: 

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods.

Abstract: 

BACKGROUND: Cisplatin-induced ototoxicity is related to oxidative stress. Astaxanthin is one of the most powerful antioxidants in nature.AIMS/OBJECTIVES: To investigate the protective effect of astaxanthin on cisplatin-induced ototoxicity.MATERIALS AND METHODS: Thirty-five Sprague Dawley female rats were divided into 5 groups: control, cisplatin, and cisplatin with 10, 20, and 40 mg/kg astaxanthin groups. Cisplatin group received a single intraperitoneal injection of 14 mg/kg cisplatin. While saline was administered in the control group, in the other 3 groups, 10, 20, and 40 mg/kg daily doses of astaxanthin were administered through orogastric cannula before administration of cisplatin. Baseline and 10th day otoacoustic emission tests were administered. An intracardiac blood sample was taken to measure total antioxidant capacity (TAC), and the cochleas of the animals were investigated histopathologically.RESULTS: Hearing level of astaxanthin 40 mg/kg + cisplatin group was higher at 24 kHz and 32 kHz frequencies compared to the cisplatin group. The TAC value of the cisplatin group was lower than both the control and astaxanthin + cisplatin groups (

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PMID: 

Food Chem Toxicol. 2019 Jul ;129:13-21. Epub 2019 Apr 20. PMID: 31014900

Abstract Title: 

Cyanidin-3-O-glucoside protects against cadmium-induced dysfunction of sex hormone secretion via the regulation of hypothalamus-pituitary-gonadal axis in male pubertal mice.

Abstract: 

Cadmium (Cd) has been generally recognized as an endocrine-disrupting chemical for its toxic effects on the hypothalamus-pituitary-gonadal (HPG) axis accompanied by dysfunction in sex hormone secretion. Particularly, exposure to Cd during puberty versus post-puberty exhibits differing age-dependent effects that require further examination. This study sought to determine if cyanidin-3-O-glucoside (C3G), a typical anthocyanin with neuroprotective bioactivity, could protect against Cd-induced sex hormone-disorder in Pubertal male mice. C3G treatment reversed the disruption of hormone levels and increased Gnrh1 gene expression in the hypothalamus. In addition, the levels of gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), were reversed by C3G. Interestingly, C3G improved the expression of LH and FSH receptor in the testis in mice exposed to Cd. Furthermore, C3G activated the signaling pathway related to the synthesis of testosterone processing. In conclusion, C3G protected against Cd-induced dysfunction of sex hormone secretion through the regulation of the HPG axis in male mice during puberty. The results of this study suggest that consumption of anthocyanins can be protective against metal-induced male reproductive dysfunction.

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PMID: 

Inflamm Bowel Dis. 2019 Aug 20 ;25(9):1510-1521. PMID: 31107535

Abstract Title: 

Low Dose of Cyanidin-3-O-Glucoside Alleviated Dextran Sulfate Sodium-Induced Colitis, Mediated by CD169+ Macrophage Pathway.

Abstract: 

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract in which excessive activation of inflammatory response is correlated. Cyanidin-3-O-glucoside (C3G) is a powerful anti-inflammatory agent, widely existing in fruits and vegetables. However, the role of C3G has rarely been investigated in dextran sulfate sodium (DSS)-induced colitis.METHODS: In an attempt to elucidate the possible mechanism of IBD and develop new efficient therapeutic methods for colitis, we evaluated the effects of C3G on DSS-induced colitis. DSS-induced colitic C57BL/6 mice were intraperitoneal injected with 1ug C3G or phosphate buffer every 2 days, a total of 3 times; the changes in macrophages and regular T cells were analyzed by flow cytometry and immunofluorescence. Cytokines and chemokines were measured by real-time quantitative polymerase chain reaction.RESULTS: The results showed that C3G treatment did not cause changes in body weight and colon length as much as those of DSS-treated mice only. Cytokine expression levels such as interleukin (IL)- 6, IL-1β, IL-18, tumor necrosis factor α, interferon γ (IFN γ) in colons and mesenteric lymph nodes (mLNs) from C3G-treated mice were lower than those from colitic mice. Meanwhile, C3G injection inhibited the decrease in CCL22 levels and Tregs induction in colitic mice. Furthermore, the activation of macrophages by LPS and increase of CD169+ cells induced by type I IFN could be inhibited by C3G directly in vitro.CONCLUSIONS: The study is the first to demonstrate strong effects of C3G to alleviate DSS-induced colonic damage in mice. The effect of C3G on DSS-induced colitis clearly showed a decrease of CD169+ macrophages in both the colon and mLNs. An increase of CD169+ cells induced by type I IFN could be inhibited by C3G. All these data suggest that the role of C3G in colitic inflammation was mediated at least partially by CD169+ cells and the type I IFN pathway.

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PMID: 

J Food Sci. 2019 Jun ;84(6):1638-1645. Epub 2019 May 29. PMID: 31141616

Abstract Title: 

Antioxidant and Antiproliferative Activities of Cyanidin-3-O-Glucoside (C3G) Liposome in Caco-2 Cells Cultivated in 2D and 3D Cell Culture Models.

Abstract: 

The aim of this study was to obtain adequate and detailed information about the antioxidant and antiproliferative activities of C3G and C3G liposomes in different cell culture models. The Caco-2 cells were cultured in 2D and 3D cell culture models, the HOwas used to construct the cell damage model and then the cells treated with C3G and C3G liposomes. The antioxidant activity and antiproliferative activities of C3G liposomes on Caco-2 cells were investigated. We observed the morphology of cells and measured the cell viability, the activity of glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and the content of malondialdehyde (MDA) in Caco-2 cells treated with HO, C3G, and C3G liposomes. The results showed that the Caco-2 cells cultured in the 3D culture model formed a 3D structure and tight spheroids and showed the increase of cell activity in 3D cell culture model, compared with the 2D cell culture model. The C3G and C3G liposomes can enhance the activities of GSH, SOD, and T-AOC but decrease the MDA content after HOtreatment, while the changes were different in 2D and 3D cells culture models. This study revealed that the results obtained from the 2D cell model may be inaccurate compared with the results obtained from the 3D cell model. PRACTICAL APPLICATION: The results of this study showed that the results obtained from the 2D cell model may be inaccurate compared with the results obtained from the 3D cell model. Our work provides a method for evaluating antioxidant activity of C3G liposomes in different cell models and provided certain theoretical basis for the follow-up research.

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PMID: 

BMC Complement Altern Med. 2019 Sep 5 ;19(1):242. Epub 2019 Sep 5. PMID: 31488210

Abstract Title: 

Cyanidin-3-rutinoside acts as a natural inhibitor of intestinal lipid digestion and absorption.

Abstract: 

BACKGROUND: Cyanidin-3-rutinoside (C3R), a naturally occurring anthocyanin, possesses anti-oxidant, anti-hyperglycemic, anti-glycation and cardioprotective properties. However, its mechanisms responsible for anti-hyperlipidemic activity have not been fully identified. The aim of the study was to investigate the lipid-lowering mechanisms of C3R through inhibition of lipid digestion and absorption in vitro.METHODS: The inhibitory activity of C3R against pancreatic lipase and cholesterol esterase was evaluated using enzymatic fluorometric and enzymatic colorimetric assays, respectively. An enzyme kinetic study using Michaelis-Menten and the derived Lineweaver-Burk plot was performed to understand the possible types of inhibition. The formation of cholesterol micelles was determined using the cholesterol assay kit. The bile acid binding was measured using the colorimetric assay. The NBD cholesterol uptake in Caco-2 cells was determined using fluorometric assay. The mRNA expression of cholesterol transporter (Niemann-Pick C1-like 1) was determined by RT-PCR.RESULTS: The results showed that C3R was a mixed-type competitive inhibitor of pancreatic lipase with the ICvalue of 59.4 ± 1.41 μM. Furthermore, C3R (0.125-1 mM) inhibited pancreatic cholesterol esterase about 5-18%. In addition, C3R inhibited the formation of cholesterol micelles and bound to primary and secondary bile acid. In Caco-2 cells, C3R (12.5-100 μM) exhibited a significant reduction in cholesterol uptake in both free cholesterol (17-41%) and mixed micelles (20-30%). Finally, C3R (100 μM) was able to suppress mRNA expression of NPC1L1 in Caco-2 cells after 24 h incubation.CONCLUSIONS: The present findings suggest that C3R acts as a lipid-lowering agent through inhibition of lipid digestion and absorption.

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PMID: 

Front Pharmacol. 2016 ;7:301. Epub 2016 Sep 7. PMID: 27656146

Abstract Title: 

Protective Effect of Cyanidin-3-O-Glucoside against Ultraviolet B Radiation-Induced Cell Damage in Human HaCaT Keratinocytes.

Abstract: 

Ultraviolet radiation is the major environmental harmful factor that has emotional impact on human skin. The aim of the present study was to determine the mechanism of protection of cyanidin-3-O-glucoside against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes. Our results show that cyanidin-3-O-glucoside decreased the levels of intracellular reactive oxygen species generated by UVB treatment. Cyanidin-3-O-glucoside also decreased the UVB-augmented levels of the DNA damage indicators phospho-p53 and phospho-ATM/ATR. In addition, cyanidin-3-O-glucoside protected keratinocytes from UVB-induced injury by overturning the disruption of mitochondrial membrane potential and reversing apoptosis. The expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was attenuated in UVB-exposed cells but restored in UVB/cyanidin-3-O-glucoside-treated cells. Furthermore, expression of the proapoptotic proteins Bcl-2-associated X (Bax) and the key apoptosis executer cleaved caspase-3 were increased in UVB-irradiated cells and decreased in UVB/cyanidin-3-O-glucoside-treated cells. For these reasons, the results demonstrate that cyanidin-3-O-glucoside protects human keratinocytes against UVB-induced oxidative stress and apoptosis. Our study provides a theoretical basis for the use of cyanidin-3-O-glucoside in the fight against light damage.

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PMID: 

Food Chem Toxicol. 2018 Oct ;120:104-111. Epub 2018 May 25. PMID: 29803697

Abstract Title: 

Cyanidin ameliorates endotoxin-induced myocardial toxicity by modulating inflammation and oxidative stress through mitochondria and other factors.

Abstract: 

Cyanidin, an anthocyanin pigment, demonstrates anti-oxidant and anti-inflammatory properties. Here, we examined the mechanistic role of cyanidin in endotoxin induced myocardial injury in inflammation and oxidative stress. In lipopolysaccharide (LPS) induced myocardial injury model, cyanidin ameliorated cardiac injury (Lactate dehydrogenase or LDH, Creatine Kinase or CK, cardiac troponin I or cTnI and cardiac myosin light chains 1 or cMLC1), cell death (caspase 3 activity and PARP activity), and improved cardiac function (ejection fraction or EF and end diastolic left ventricular inner dimension or LVID). Cyanidin also attenuated endotoxin induced myocardial injury by modulating inflammatory cytokines (Tumor necrosis factor alpha or TNFα, Interleukin-1 beta or IL-1β, macrophage inflammatory protein 2 or MIP-2 and chemokine (C-C motif) ligand 2 also known as monocyte chemoattractant protein 1 or MCP1) and oxidative stress (protein nitration). Cyanidin modulated redox homeostasis through intracellular oxidized/reduced glutathione.The most striking properties of cyanidin in endotoxin induced mediated myocardial injury was the modulation of mitochondria, its oxidative damage and associated factor Opa1 and Trx1. Thus, our study demonstrated that cyanidin as a constituent of our food chain may be beneficial and has therapeuticpotential in sepsis treatment or other myocardial oxidative and/or inflammation induced injuries.

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PMID: 

Acta Pharmacol Sin. 2018 Sep ;39(9):1439-1452. Epub 2018 Apr 19. PMID: 29671417

Abstract Title: 

Cyanidin attenuates Aβ-induced neuroinflammation by suppressing NF-κB activity downstream of TLR4/NOX4 in human neuroblastoma cells.

Abstract: 

Cyanidin is polyphenolic pigment found in plants. We have previously demonstrated that cyanidin protects nerve cells against Aβ-induced toxicity by decreasing oxidative stress and attenuating apoptosis mediated by both the mitochondrial apoptotic pathway and the ER stress pathway. To further elucidate the molecular mechanisms underlying the neuroprotective effects of cyanidin, we investigated the effects of cyanidin on neuroinflammation mediated by the TLR4/NOX4 pathway in Aβ-treated human neuroblastoma cell line (SK-N-SH). SK-N-SH cells were exposed to Aβ(10μmol/L) for 24 h. Pretreatment with cyanidin (20 μmol/L) or NAC (20 μmol/L) strongly inhibited the NF-κB signaling pathway in the cells evidenced by suppressing the degradation of IκBα, translocation of the p65 subunit of NF-κB from the cytoplasm to the nucleus, and thereby reducing the expression of iNOS protein and the production of NO. Furthermore, pretreatment with cyanidin greatly promoted the translocation of the Nrf2 protein from the cytoplasm to the nucleus; upregulating cytoprotective enzymes, including HO-1, NQO-1 and GCLC; and increased the activity of SOD enzymes. Pretreatment with cyanidin also decreased the expression of TLR4, directly improved intracellular ROS levels and regulated the activity of inflammation-related downstream pathways including NO production and SOD activity through TLR4/NOX4 signaling. These results demonstrate that TLR4 is a primary receptor inSK-N-SH cells, by which Aβtriggers neuroinflammation, and cyanidin attenuates Aβ-induced inflammation and ROS production mediated by the TLR4/NOX4 pathway, suggesting that inhibition of TLR4 by cyanidin could be beneficial in preventing neuronal cell death in the process of Alzheimer's disease.

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PMID: 

Neural Regen Res. 2016 May ;11(5):795-800. PMID: 27335564

Abstract Title: 

Cyanidin suppresses amyloid beta-induced neurotoxicity by inhibiting reactive oxygen species-mediated DNA damage and apoptosis in PC12 cells.

Abstract: 

Amyloid beta (Aβ)-induced oxidative stress is a major pathologic hallmark of Alzheimer's disease. Cyanidin, a natural flavonoid compound, is neuroprotective against oxidative damage-mediated degeneration. However, its molecular mechanism remains unclear. Here, we investigated the effects of cyanidin pretreatmentagainst Aβ-induced neurotoxicity in PC12 cells, and explored the underlying mechanisms. Cyanidin pretreatment significantly attenuated Aβ-induced cell mortality and morphological changes in PC12 cells. Mechanistically, cyanidin effectively blocked apoptosis induced by Aβ, by restoring the mitochondrial membrane potential via upregulation of Bcl-2 protein expression. Moreover, cyanidin markedly protected PC12 cells from Aβ-induced DNA damage by blocking reactive oxide species and superoxide accumulation. These results provide evidence that cyanidin suppresses Aβ-induced cytotoxicity, by preventing oxidative damage mediated by reactive oxide species, which in turn inhibits mitochondrial apoptosis. Our study demonstrates the therapeutic potential of cyanidin in the prevention of oxidative stress-mediated Aβ neurotoxicity.

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PMID: 

J Food Sci Technol. 2016 Feb ;53(2):968-76. Epub 2016 Jan 25. PMID: 27162376

Abstract Title: 

Cyanidin inhibits quorum signalling pathway of a food borne opportunistic pathogen.

Abstract: 

Quorum sensing (QS) is the process of population dependent cell to cell communication used by bacteria to regulate their phenotypic characteristics. Key virulence factors that determine the bacterial pathogenicity and food spoilage were found to be regulated by QS mechanism. Hence, disrupting the QS signaling pathway could be an attractive strategy to manage food borne pathogens. In the current study, QS inhibitory activity of a naturally occurring anthocyanin-cyanidin and its anti-biofilm property were assessed against an opportunistic pathogen Klebsiella pneumoniae, using a bio-sensor strain. Further, QS inhibitory property of a naturally occurring anthocyanin cyanidin was further confirmed using in-silico techniques like molecular docking and molecular dynamics simulation studies. Cyanidin at sub-lethal dose significantly inhibited QS-dependent phenotypes like violacein production (73.96 %), biofilm formation (72.43 %), and exopolysaccharide production (68.65) in a concentration-dependent manner. Cyanidin enhanced the sensitivity of test pathogen to conventional antibiotics in a synergistic manner. Molecular docking analysis revealed that cyanidin binds more rigidly with LasR receptor protein than the signaling compound with a docking score of -9.13 Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity occurs through the conformational changes between the receptor and cyanidin complex. Our results indicate that cyanidin, can be a potential QS based antibiofilm and antibacterial agent for food borne pathogens.

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