iridoids and Diabetes-Mellitus

At present, the potential of natural products in new drug development has attracted more and more scientists' attention, and natural products have become an important source for the treatment of various diseases or important lead compounds. Geniposide, as a novel iridoid glycoside compound, is an active natural product isolated from the herb

Topics: Biological Products; Diabetes Mellitus; Gardenia; Iridoids

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

Geniposide, an iridoid glucoside, is a major component in the fruit of

Topics: Animals; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus; Drug Evaluation, Preclinical; Humans; Iridoids; Models, Molecular

The overall health beneficial action of olive oil phenolic components is well established. Recent studies have elucidated the biological effects of two isolated compounds, namely oleuropein and hydroxytyrosol, with particular attention on their antioxidant activity. Thus, a protective action has been demonstrated in preclinical studies against several diseases, especially cardiovascular and metabolic disorders. The present review will describe the biological effects of oleuropein and hydroxytyrosol, with particular attention on the molecular mechanism underlying the protective action on cardiovascular and metabolic alterations, as demonstrated by in vitro and in vivo experimental studies performed with the isolated compounds.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus; Humans; Iridoid Glucosides; Iridoids; Metabolic Diseases; Olive Oil; Phenylethyl Alcohol; Plant Oils

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Iridoids; Kidney; Male; Mice; Signal Transduction

Topics: alpha-Glucosidases; Animals; Cattle; Diabetes Mellitus; Iridoids; Oleaceae; Plant Extracts

Metabolic disorder particularly diabetes is one of the leading causes of psychiatric or other neurodegenerative diseases. Previous clinical and pre-clinical studies indicate anti-diabetic drugs such as GLP-1 analogs or GLP-1 receptor (GLP-1R) agonists could perform the neuroprotective effects with multiple molecular mechanisms. As one of natural compound to stimulate GLP-1R, geniposide was reported could improve cognitive behaviors in diabetes associated Alzheimer's disease rat model. Stimulating of GLP-1R could act the crosstalk downstream like neurotrophic factor mediated cAMP-response element binding protein (CREB) would be activated and exert cellular events including promotion of adult neurogenesis, which is one of important treatment targets in antidepressant. Here in this study, we employed HDF in combined with corticosterone (CORT) treatment to create diabetes associated depression model. Geniposide treatment could not only correct the metabolic pattern but could also improve the cognitive dysfunctions and depressive/anxiety symptoms. In consistent with its pro-neurogenic effects, geniposide also enhanced the activity of CREB in hippocampal tissue. Moreover, blocking CREB activity with 666-15 significantly compromised the effects of geniposide in promotion of neurogenesis and behavioral protective effects. In conclusion, this study expands the application of geniposide to treat diabetes associated depression subject and identified the underlying molecular mechanism for such effects.

Topics: Animals; Cyclic AMP Response Element-Binding Protein; Depression; Diabetes Mellitus; Iridoids; Mice; Neurogenesis; Rats

The purpose of the present study was to elucidate the pharmacological effects of Geniposide (GEN) on high diet fed and streptozotocin (STZ)-caused diabetic cognitive impairment. The mice were fed with high fat diet (HFD) for 4 weeks and intraperitoneally injected with 60 mg/kg STZ for three times within 72 h. The mice with glucose level over 15 mmol/l were regarded as diabetic and selected for further studies. The animals were intragastrically treated with metformin or GEN once daily for 4 weeks. Afterwards, the animals were applied for Y maze, novel object recognition (NOR) test, step-through passive avoidance test, and Morris water maze (MWM) test. The blood glucose and body weight were examined. The SH-SY5Y cells were treated with GEN in the presence or absence of ibrutinib and stimulated with high-glucose culture medium. The tumor necrosis factor-a (TNF-α) and interleukin (IL)-6 in serum, hippocampus, and supernatant were measured using ELISA method. The protein expressions of Bruton's tyrosine kinase (BTK), Toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), nuclear factor kappa-B (NF-κB), p-NF-κB, brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB), p-CREB, and glucagon-like peptide-1 receptor (GLP-1R) were detected by western blot analyses. As a result, the GEN treatment notably attenuated the body weight, blood glucose, and cognitive decline. GEN also inhibited the generations of inflammatory cytokines. Furthermore, the administrations of GEN ameliorated the alterations of BTK, TLR4, MyD88, NF-κB, and BDNF in HFD + STZ-induced mice. With the application of ibrutinib, the selective inhibitor of BTK, it was also found that BTK/TLR4/NF-κB pathway was associated with the GEN treatment in high glucose-induced SH-SY5Y cells. In summary, the results suggested that GEN exerted the protective effect on STZ-induced cognitive impairment possibly through the modulation of BTK/TLR4/NF-κB signaling.

Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Blood Glucose; Cell Line, Tumor; Cognitive Dysfunction; Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Iridoids; Male; Mice; Mice, Inbred ICR; NF-kappa B; Random Allocation; Signal Transduction; Streptozocin; Toll-Like Receptor 4; Treatment Outcome

The current study was designed to investigate the protective role of geniposide (GE) in liver injury in diabetic C57BL/KsJ-db/db mice and to explore the underlying mechanisms. The oral glucose tolerance test was performed, and the levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined. The levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor-α were decreased by GE, metformin and fasudil in diabetic db/db mice. Western blotting analysis showed that the expression levels of Rho, ROCK1, ROCK2, p-NF-κBp65 and p-IκBα were significantly reversed by GE treatment. These findings demonstrated that GE exhibits a protective effect on diabetic hepatic inflammation.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Cholesterol; Cytokines; Diabetes Mellitus; Insulin; Iridoids; Liver; Mice, Inbred C57BL; rho-Associated Kinases; Triglycerides