oleuropein and Diabetic-Nephropathies

The global pandemic of diabetes and diabetes complications confers heavy pressure on public health. Novel antidiabetes strategies with negligible unwanted effects are urgently needed. Currently, the anti-hyperglycemic potential of plant-based functional ingredients has been explored to provide alternative strategies. As a kind of dietary bioactive compound, oleuropein has aroused the growing interest of researchers in diabetes and diabetes complications management. This review reveals the research progress of oleuropein in treating diabetes and diabetes complications and summarizes the molecular mechanisms involved in these beneficial effects of oleuropein. Oleuropein achieves amelioration of diabetes, the mechanisms of which include the modulation of insulin secretion, the repairment islet morphology, the activation of hepatic AMP-activated protein kinase singling, and the improvement of glucose tolerance and insulin resistance. Oleuropein also can relieve diabetes complications including diabetic nephropathy, diabetes cardiovascular complications, diabetic retinopathy, poor wound healing, diabetic neuropathy, and diabetic testicular dysfunction. Oleuropein reverses cell apoptosis, regenerates tissues, restores the histological organization, and decreases oxidative stress in treating diabetes complications. Taken together, oleuropein is a promising compound for diabetes and diabetes complications management and can be used as a nutraceutical to fight against these diseases.

Topics: Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Humans; Iridoid Glucosides; Iridoids; Oxidative Stress

Oleuropein, the most prevalent polyphenol in olives, exerts many positive impacts on human health, including counteracting cancer. However, the effect of oleuropein on diabetic nephropathy (DN) progression remains elusive.. A total of three groups of mice were used in our study. Two groups of db/db mice fed with or without oleuropein. A group of wide-type mice fed with normal diet was used as normal control. After ten weeks of treatment, the body weight, biochemical parameters, oxidative stress markers, inflammatory cytokines levels, and kidney injury status were measured.. Our results demonstrated that oral administration of oleuropein reduced body weight, alleviated kidney injury, and decreased oxidative stress and inflammatory response in db/db mice. The oleuropein inhibited cell apoptosis via regulation of MAPK signalling pathways and its downstream targets Bax, caspase-3, and Bcl-2 expression.. Oleuropein may server as a favourable additional agent for the treatment of patients with DN.

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Humans; Iridoid Glucosides; Mice; Olea; Oxidative Stress

Podocyte injuries are associated with progression of diabetic nephropathy (DN). Apelin, an adipocyte-derived peptide, has been reported to be a promoting factor for DN. In this study, we aim to determine whether apelin promotes progression of DN by inducing podocyte dysfunction. kk-Ay mice were used as models for DN. Apelin and its antagonist, F13A were intraperitoneally administered for 4 weeks, respectively. Renal function and foot process proteins were analysed to evaluate the effects of apelin on kk-Ay mice and podocytes. Apelin increased albuminuria and decreased podocyte foot process proteins expression in kk-Ay mice, which is consistent with the results that apelin receptor (APLNR) levels increased in glomeruli of patients or mice with DN. In cultured podocytes, high glucose increased APLNR expression and apelin administration was associated with increased permeability and decreased foot process proteins levels. All these dysfunctions were associated with decreased 26S proteasome activities and increased polyubiquitinated proteins in both kk-Ay mice and cultured podocytes, as demonstrated by 26S proteasome activation with cyclic adenosine monophosphate (cAMP) or oleuropein. These effects seemed to be related to endoplasmic reticulum (ER) stress, as apelin increased C/EBP homologous protein (CHOP) and peiFα levels while cAMP or oleuropein reduced it in high glucose and apelin treated podocytes. These results suggest that apelin induces podocyte dysfunction in DN through ER stress which was induced by decreased proteasome activities in podocytes.

Topics: Albumins; Animals; Apelin Receptors; Basement Membrane; Cell Membrane Permeability; Creatinine; Cyclic AMP; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endoplasmic Reticulum Stress; Female; Glucose; Humans; Intercellular Signaling Peptides and Proteins; Iridoid Glucosides; Iridoids; Kidney; Kidney Function Tests; Male; Mice, Inbred C57BL; Middle Aged; Podocytes; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Receptors, G-Protein-Coupled