title: Cyanidin-3-glucoside isolated from mulberry fruit protects pancreatic β-cells against oxidative stress-induced apoptosis.
abstract: The extract obtained from berries contains high amounts of anthocyanins, and this extract is used as a phytotherapeutic agent for different types of diseases. In this study, we examined the cytoprotective effects of cyanidin-3-glucoside (C3G) isolated from mulberry fruit against pancreatic β-cell apoptosis caused by hydrogen peroxide (H2O2)-induced oxidative stress. The MIN6 pancreatic β-cells were used to investigate the cytoprotective effects of C3G on the oxidative stress-induced apoptosis of cells. Cell viability was examined by MTT assay and lipid peroxidation was assayed by thiobarbituric acid (TBA) reaction. Immunofluorescence staining, flow cytometry and western blot analysis were also used to determine apoptosis and the expression of proteins associated with apoptosis. Our results revealed that H2O2 increased the rate of apoptosis by stimulating various pro-apoptotic processes, such as the generation of intracellular reactive oxygen species (ROS), lipid peroxidation, DNA fragmentation and caspase-3 activation. However, C3G reduced the H2O2-induced cell death in the MIN6N pancreatic β-cells. In addition, we confirmed that H2O2 activated mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. C3G inhibited the phosphorylation of ERK and p38 without inducing the phosphorylation of JNK. Furthermore, C3G regulated the intrinsic apoptotic pathway-associated proteins, such as proteins belonging to the Bcl-2 family, cytochrome c and caspase-3. Taken together, our results suggest that C3G isolated from mulberry fruit has potential for use as a phytotherapeutic agent for the prevention of diabetes by preventing oxidative stress-induced β-cell apoptosis.
authors.affiliation: National Institute of Biological Resources, Incheon 404-708, Republic of Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Bioengineering and Technology, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Bioengineering and Technology, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Song
authors.affiliation: Department of Bioengineering and Technology, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Suk-Jin
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Seongnam, Gyeonggi-do 463-746, Republic of Korea.
authors.forename: Young Eon
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicinal Materials and Processing, Kyung Hee University, Yongin, Gyeonggi-do 446-701, Republic of Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Department of Bioengineering and Technology, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Eock Kee
authors.initials: EK
authors.lastname: Hong
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005638:Fruit / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D031625:Morus / Q000737:chemistry*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D016877:Oxidants; C462279:cyanidin-3-O-beta-glucopyranoside; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3