morin and Diabetes-Mellitus--Type-2

Studies have shown that exposure to air pollutants such as diesel exhaust particles (DEP) exacerbate diabetes complications. Morin hydrate (MH), a plant bioflavonoid, provides hepatoprotection due to its diverse pharmacological properties. This study examines the hepatoprotective effects of MH in Wistar rats with type 2 diabetes exposed to diesel exhaust (DE). Procured male Wistar rats (n = 60) were separated into 12 groups of five rat each. Type 2 diabetes was induced following oral therapy with fructose solution and one-time injection of 45 mg/kg of streptozotocin (STZ). The DEP extract was administered by nasal instillation, whereas MH was administered via oral gavage. Biochemical assays were used to determine the effect of MH on diabetic rats and DEP-exposed diabetic rats with respect to liver function indices (AST and ALT), liver antioxidants (SOD, CAT, Gpx, and GSH), lipid profile, and oxidative stress marker (conjugated diene and lipid peroxidation). The mRNA expression of PI3K/AKT/GLUT4 and AMPK/GLUT4 signaling pathways were quantified using RT-PCR. The results show that normal rats, diabetic rats, and diabetic rats exposed to DEP exhibited a substantial decrease in oxidative stress indicators, serum lipid profile, and levels of AST and ALP, as well as an increase in liver natural antioxidants following oral administration of MH. The gene expression study demonstrated that MH promotes the activation of the insulin signaling pathways which facilitates the uptake of glucose from the blood. This study suggests that MH offered hepatoprotection in type 2 diabetic rats and DEP exposed diabetic rats.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Flavonoids; Lipids; Oxidative Stress; Phosphatidylinositol 3-Kinases; Rats; Rats, Wistar; Vehicle Emissions

Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation.. In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated.. The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism.. In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling.. This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.

Topics: 1-Deoxynojirimycin; Animals; Diabetes Mellitus, Type 2; Drug Combinations; Flavonoids; Insulin; Insulin Resistance; Lipids; Mice; PPAR gamma; Prediabetic State

Hyperglycemia associated ER stress has been found as a critical contributor in the pathogenesis of type 2 diabetes mellitus. However, reports regarding molecular mechanisms involved are limited. This study was aimed to identify the role of ER stress in regulating hepatic glucose metabolism and its link with oxidative stress. Further, this study explores the novel role of Morin, a flavonol, in modulating ER stress in STZ/nicotinamide induced type 2 diabetic male Wistar rats. Results demonstrate that hyperglycemia induced ER stress in rats and significantly lowered the expression of glucose transporter proteins resulting in impaired glucose metabolism during diabetes. Morin was found to downregulate PERK-eIF2α-ATF4 pathway by interacting with PERK protein as confirmed through pull-down assay. Additionally, Morin maintained the reducing environment in ER and enhanced PDI activity compared to diabetic rats. Morin prevented cell death by suppressing the expression of PERK dependent pro-apoptotic proteins including ATF4 and CHOP. Findings from this study affirm the role of ER stress in hyperglycemia induced gluco-metabolic aberrations and liver injury as confirmed by ISRIB, a standard chemical ER stress inhibitor. Notably, Morin promoted deactivation of UPR sensors and upregulated PDI activity endorsing its anti-ER stress potential which may allow the development of new therapeutic avenues to target hyperglycemic hepatotoxicity.

Topics: Activating Transcription Factor 4; Animals; Antioxidants; Apoptosis; Chronic Disease; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Down-Regulation; eIF-2 Kinase; Endoplasmic Reticulum Stress; Flavonoids; Hyperglycemia; Liver Diseases; Male; Rats; Rats, Wistar; Streptozocin

The present study deals with the synthesis, characterization of zinc-morin complex and evaluation of its antidiabetic efficacy in High Fat Diet (HFD)-fedStreptozotocin (STZ) induced diabetic rats. Oral administration of zinc-morin complex to diabetic rats (5mg/kg body weight/day) for a period of 30 days resulted in the decreased levels of blood glucose and HbA1c. Oral administrations of the zinc-morin complex for 30 days significantly improved hyperglycemia, glucose intolerance, and insulin resistance. The elevated levels of lipid peroxides declined and the antioxidant competence was found to be improved in diabetic rats treated with the complex. The status of the lipid and lipoprotein profile in the serum was normalized upon treatment. Levels of TNFα decreased upon treatment with the complex. The altered levels of adipokines such as adiponectin and leptin were normalized upon treatment with the complex. In conclusion, the present study indicates that the zinc-morin complex possesses antidiabetic, antidyslipidemic and antioxidant potentials in HFD-fedSTZ induced diabetic rats.

Topics: Adiponectin; Animals; Blood Glucose; Coordination Complexes; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Flavonoids; Glucose Tolerance Test; Glycated Hemoglobin; Insulin; Leptin; Magnetic Resonance Spectroscopy; Male; Random Allocation; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Tumor Necrosis Factor-alpha; Zinc