OBJECTIVES: This study examined the effect of cilostazol, a potent phosphodiesterase inhibitor, on the progression of neuropathies associated with streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. METHODS: Eight weeks after streptozotocin treatment, a pelleted diet containing 0.03% cilostazol (15 mg/kg body weight) was given for four weeks. Body weight, blood glucose level, motor nerve conduction velocity (MNCV), myelinated fiber density and size distribution of sciatic nerves were compared between age-matched normal rats (Group 1), control diabetic rats (Group 2) and cilostazol-treated diabetic rats (Group 3). RESULTS: Body weight was significantly reduced and blood glucose level was significantly increased in diabetic rats (Group 2 and 3) compared to normal rats. MNCV and cAMP content of sciatic nerves were significantly reduced in diabetic rats 12 weeks after streptozotocin treatment. Myelinated fiber size and density were also significantly reduced, and thickening of the capillary walls and duplication of the basement membranes of the endoneural vessels were observed in the diabetic rats. Whereas both body weight and blood glucose level of Group 3 did not differ significantly from those of Group 2, cilostazol treatment significantly increased MNCV and cAMP content of sciatic nerves in Group 3 but not to the levels observed in Group 1. MNCV positively correlated with cAMP content of sciatic nerves (r = 0.86; p < 0.001). Cilostazol treatment not only restored myelinated fiber density and size distribution but reversed some of the vascular abnormalities. CONCLUSION: These findings suggest that a reduced cAMP content in motor nerves may be involved in the development of diabetic neuropathy, and that cilostazol may prevent the progression of diabetic neuropathy by restoring functional impairment and morphological changes of peripheral nerves.
Animal ; Cyclic AMP/metabolism ; Diabetes Mellitus, Experimental/physiopathology ; Diabetes Mellitus, Experimental/drug therapy ; Diabetic Neuropathies/prevention & control* ; Diabetic Neuropathies/physiopathology ; Diabetic Neuropathies/pathology ; Male ; Neural Conduction/drug effects ; Phosphodiesterase Inhibitors/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/physiopathology ; Sciatic Nerve/pathology ; Sciatic Nerve/drug effects ; Tetrazoles/pharmacology*

OBJECTIVEThe present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats.

METHODSType 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin (35 mg/kg) and high-fat diet. Four weeks after the confirmation of diabetes, diabetic rats were treated with diosmin (50 and 100 mg/kg, p.o.) for next 4 weeks. Rats were evaluated for biochemical, behavioral and oxidative stress parameters. Eddy's hot plate and tail immersion test were performed on 6th, 7th, 8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively. Further, the walking function test was performed for assessing the motor responses at the end of the treatment schedule.

RESULTSRats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test. Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight, elevated blood sugar and lipid profiles. Further the dose-dependent improvement was observed in thermal hyperalgesia, cold allodynia and walking function in diabetic rats treated with diosmin. Elevated levels of malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment.

CONCLUSIONDiosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.

Animals ; Blood Glucose ; metabolism ; Cholesterol ; metabolism ; Citrus ; chemistry ; Diabetic Neuropathies ; drug therapy ; metabolism ; prevention & control ; Diosmin ; administration & dosage ; Glutathione ; metabolism ; Humans ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley

Huanglian Wendan decoction (HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy (DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin (STZ) + high-glucose-fat (HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels (3 and 6 g·kg). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.
Animals ; Cognition Disorders ; genetics ; metabolism ; prevention & control ; Cytokines ; genetics ; metabolism ; Diabetic Neuropathies ; drug therapy ; genetics ; metabolism ; psychology ; Drugs, Chinese Herbal ; administration & dosage ; Hippocampus ; drug effects ; metabolism ; Humans ; Insulin ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of xiaokeling concentration fluid on insulin-like growth factor-1 (IGF-1) mRNA expression in sciatic nerve of Streptozotocin-induced diabetic rats. METHODS: Thirty diabetic rats were randomly divided into model group, mecobalamin tablets group, and xiaokeling concentration fluid group. The IGF-1 mRNA level in sciatic nerve of each group was determined after 8 weeks by relative quantity RT-PCR. RESULTS: The IGF-1 mRNA level in sciatic nerve of diabetic rats between xiaokeling concentration fluid group, mecobalamin tablets group and normal group showed no significant difference ( P = 0.213, P = 0.822, P = 0.304 ), while was significantly higher than that of the model group ( P < 0.05 ). IGF-1 mRNA level was negatively correlated with the level of blood sugar (P < 0.05). CONCLUSION IGF-1 mRNA level decreased in sciatic nerve of diabetic rats. Xiaokeling concentration fluid can increase the IGF-1 mRNA level in sciatic nerve of diabetic rats. Xiaokeling concentration fluid is involved in the regulation of IGF-1 expression, and probably prevents diabetic peripheral neuropathy from deteriorating.
Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Neuropathies ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Insulin-Like Growth Factor I ; biosynthesis ; genetics ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Receptor, IGF Type 1 ; Reverse Transcriptase Polymerase Chain Reaction ; Sciatic Nerve ; metabolism

BACKGROUND/AIMS: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). METHODS: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). RESULTS: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls (40.95 +/- 5.40), HD (28.70 +/- 6.37), HD with 100 mg/kg (41.14 +/- 1.12), and HD with 250 mg/kg (48.98 +/- 7.01; p < 0.05, HD with VVE vs. HD). CONCLUSIONS: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.
Animals ; Antioxidants/*pharmacology ; Biological Markers/blood ; Blood Glucose/drug effects/metabolism ; Body Weight/drug effects ; Diabetic Neuropathies/blood/etiology/pathology/*prevention & control ; *Diet, High-Fat ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Epidermis/*innervation ; Grape Seed Extract/*pharmacology ; Lipids/blood ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/*pharmacology ; Peripheral Nerves/*drug effects/pathology ; Phytotherapy ; Plants, Medicinal ; Prediabetic State/blood/*drug therapy/etiology ; Time Factors ; *Vitis