morroniside and Diabetic-Nephropathies

Diabetes mellitus is an endocrine and metabolic disease characterized by high blood glucose. Diabetic nephropathy (DN) is one of the most typical diabetic complications. Cornus officinalis is a type of traditional Chinese medicine that replenishes the liver and kidney. Morroniside is one of the main characteristic components of C. officinalis. In this study, an in vitro model for simulating DN damage was established by stimulating rat glomerular mesangial cells by the advanced glycation end products. The protective mechanism and effect of morroniside in regulating receptor for advanced glycation end products signaling pathway in DN was investigated to provide experimental evidence for the prevention and treatment of DN.

Topics: Animals; Cells, Cultured; Cornus; Diabetic Nephropathies; Down-Regulation; Gene Expression; Glycation End Products, Advanced; Glycosides; Humans; Mesangial Cells; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phytotherapy; Rats; Receptor for Advanced Glycation End Products; Signal Transduction; Transforming Growth Factor beta

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

In our previous study, we reported the renoprotective effect of Hachimi-jio-gan, a Chinese traditional prescription consisting of eight medicinal plants, and also reported the effect of Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a component of Hachimi-jio-gan, on diabetic nephropathy using diabetic rats. In this study, we investigated the effects of morroniside isolated from Corni Fructus on renal damage in streptozotocin-treated diabetic rats. Oral administration of morroniside at a dose of 20 or 100 mg/kg body weight/d for 20 d to diabetic rats resulted in significant decreases in increasing serum glucose and urinary protein levels. Moreover, the decreased levels of serum albumin and total protein in diabetic rats were significantly increased by morroniside administration at a dose of 100 mg/kg body weight/d. In addition, morroniside significantly reduced the elevated serum urea nitrogen level and showed a tendency to reduce creatinine clearance. Morroniside also significantly reduced the enhanced levels of serum glycosylated protein, and serum and renal thiobarbituric acid-reactive substances. Protein expressions related to the advanced glycation endproduct (AGE) level and actions, oxidative stress such as N(epsilon)-(carboxyethyl)lysine, as well as receptors for AGE and heme oxygenase-1 were increased in diabetic rats, but the levels were also significantly decreased by the administration of morroniside. This suggests that morroniside exhibits protective effects against diabetic renal damage by inhibiting hyperglycemia and oxidative stress. These results indicate that morroniside is one component partly responsible for the protective effects of Corni Fructus and Hachimi-jio-gan against diabetic renal damage.

Topics: Animals; Blood Glucose; Blotting, Western; Cornus; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Drinking; Eating; Glycosides; Glycosylation; Hypoglycemic Agents; Insulin; Kidney; Kidney Cortex; Male; Mitochondria; Organ Size; Proteinuria; Rats; Rats, Wistar; Serum Albumin; Thiobarbituric Acid Reactive Substances; Urodynamics

Advanced glycation end products (AGE) are involved in the alterations of renal mesangial cell (MCs) growth, a feature of early stages of diabetic nephropathy (DN). We postulate that morroniside and loganin, 2 components extracted from Cornus officinalis, may ameliorate the detrimental effects of AGE-induced MCs proliferation by preventing oxidative stress. Rat MCs cultured in AGE milieu were treated with morroniside and loganin. Results showed that morroniside and loganin inhibited AGE-induced MC proliferation as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Fluorescence microscopy revealed that the morroniside and loganin improved the morphological changes of MCs. Flow cytometric analysis showed that morroniside and loganin inhibited the cell cycle of rat MCs. Furthermore, the level of reactive oxygen species was significantly reduced, and the activities of superoxide dismutase and glutathione peroxidase were markedly increased, whereas the level of malondialdehyde was not significantly reduced. These results suggest that morroniside and loganin regulate MC growth by preventing oxidative stress. Thus, this study provides a molecular basis for the use of morroniside and loganin in the early stages of DN.

Topics: Animals; Antioxidants; Cell Cycle; Cell Line; Cell Proliferation; Cell Shape; Cornus; Diabetic Nephropathies; Flow Cytometry; Glutathione Peroxidase; Glycation End Products, Advanced; Glycosides; Iridoids; Malondialdehyde; Mesangial Cells; Microscopy, Fluorescence; Oxidative Stress; Rats; Reactive Oxygen Species; Superoxide Dismutase