morroniside and Diabetes-Mellitus--Type-2

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.

Topics: Animals; Antioxidants; Apoptosis; Blood Glucose; Cornus; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Glycosides; Heme Oxygenase-1; Histones; Hypoglycemic Agents; Inflammation; Iridoid Glycosides; Liver; Liver Function Tests; Male; Mice; Mice, Inbred C57BL; Molecular Targeted Therapy; NF-E2-Related Factor 2; Oxidative Stress; Phytotherapy; Plant Preparations; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Transcription Factor RelA

The effects of morroniside isolated from Corni Fructus on renal lipids and inflammation provoked by hyperglycaemia were investigated using type 2 diabetic mice.. Morroniside was administered orally to db/db mice at 20 or 100 mg/kg daily for 8 weeks, and its effects were compared with those in vehicle-treated db/db and m/m (non-diabetic) mice. Serum and renal biochemical factors and protein expression related to lipid homeostasis and inflammation were measured.. Morroniside produced significant dose-dependent reductions in serum triglyceride and renal glucose and lipid levels. Morroniside altered the abnormal protein expression of sterol regulatory element binding proteins (SREBP-1 and SREBP-2). In addition, the formation of reactive oxygen species and lipid peroxidation were inhibited in the morroniside-treated db/db mouse group, and the ratio of reduced glutathione to the oxidised form was significantly elevated. These results suggest that morroniside alleviated oxidative stress in the kidneys of db/db mice. Furthermore, 100 mg/kg morroniside down-regulated the expression of nuclear factor-kappaBp65, cyclooxygenase-2 and inducible nitric oxide synthase augmented in db/db mice.. Morroniside may inhibit abnormal lipid metabolism and inflammation due to reactive oxygen species in the kidneys in type 2 diabetes.

Topics: Animals; Biomarkers; Cornus; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Fruit; Glucose; Glycosides; Inflammation; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type I; Oxidative Stress; Plants, Medicinal; Sterol Regulatory Element Binding Proteins; Transcription Factor RelA; Triglycerides