title: Evaluation of morroniside, iridoid glycoside from Corni Fructus, on diabetes-induced alterations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice.
abstract: The present study was conducted to examine whether morroniside has an ameliorative effect on diabetes-induced alterations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice. Morroniside (20 or 100 mg/kg body weight/d, per os (p.o.)) was administered every day for 8 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. The administration of morroniside decreased the elevated serum glucose concentration in db/db mice, and reduced the increased oxidative biomarkers including the generation of reactive oxygen species and lipid peroxidation in the liver. The db/db mice exhibited the up-regulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, NF-E2-related factor 2 (Nrf2), heme oxygenase-1, nuclear factor-kappa B, cyclooxygenase-2, inducible nitric oxide synthase, monocyte chemotactic protein-1, and intracellular adhesion molecule-1 levels in the liver; however, morroniside treatment significantly reduced those expressions. Moreover, the augmented expressions of apoptosis-related proteins, Bax and cytochrome c, were down-regulated by morroniside administration. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of db/db mice improved on morroniside administration. Taking these into consideration, our findings support the therapeutic evidence for morroniside ameliorating the development of diabetic hepatic complications via regulating oxidative stress, inflammation, and apoptosis.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930–0194, Japan.
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Noh
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D029768:Cornus; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006657:Histones / Q000032:analysis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D057889:Iridoid Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D051267:NF-E2-Related Factor 2 / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D028321:Plant Preparations / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051996:Transcription Factor RelA / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D006027:Glycosides; D006657:Histones; D007004:Hypoglycemic Agents; D057889:Iridoid Glycosides; D051267:NF-E2-Related Factor 2; D028321:Plant Preparations; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D051996:Transcription Factor RelA; C488401:morroniside; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2