The Togolese Medicinal Recipe, Diabeto-Dolvo® Exerted Antidiabetic Effects in Wistar Rats

Objective: this study was to evaluate the toxicity of a herbal recipe Diabeto-Dolvo® (DD) and its efficacy in streptozotocin-induced diabetic Wistar rats. Methodology and results: The toxicity test was performed by oral administration of the extract to rats while diabetes was induced with streptozotocin, the 250, and 500 mg / kg body weight. The results of the toxicity tests revealed no evidence of mortality or morbidity suggesting an LD50 greater than 5000 mg / kg. Similarly, the biochemical and haematological parameters remained unchanged. In antidiabetic tests, there was a progressive decrease followed by a normalization of the glucose level of the treated rats. Overall, the extract at 250 and 500 mg / kg body weight resulted in a significant reduction in glycated haemoglobin, amylase, lipase, G6PD and serum lipids. Conclusion and application of results: This study revealed that, the treatment with the recipe might repair oxidative damages, hyperglycaemia and hyperlipidaemia in diabetic rats in the same way as the treatment with glibenclamide. This study is a contribution to the experimental validation of the DD recipe. In research and development application, the DD recipe will be used in the treatment of cases of diabetes mellitus. A natural product, it will support the multiple treatments of so-called conventional medicine, relatively expensive for the population. Key words: Diabeto-Dolvo®; blood glucose; oxidative damage; streptozotocin; diabetes mellitus; Togo.

Radix Dipsaci extract protects against Rosiglitazone induced bone loss

The dried root of Dipsacus asperoides is known as Radix Dipsaci extract(RDE). It's a kidney-toning herbal medication with a lengthy track record of safe usage in the treatment of bone fractures and joint disorders. The drug rosiglitazone (RSG) causes an imbalance in bone remodelling, which results in increased apoptotic death of osteogenic cells and decreased bone production. The goal of this study was to investigate the effects of RDE on RSGinduced bone loss in diabetic rats in a systematic way. Five groups of six Wistar albino rats were studied: control (vehicle therapy), Streptozotocin (diabetes) group, RDE group, Rosiglitazone, and Rosiglitazone +RDE group. Insulin, oxidative stress, and bone turnover markers in the blood were all detected using ELISA tests. When compared to diabetic control rats, RDE therapy significantly raised insulin and osteocalcin levels. RDE may be able to prevent diabetic osteoporosis by boosting osteogenesis and lowering oxidative stress in the bone.These findings support the use of RDE as a bone loss inhibiting in diabetics. Well-designed clinical trials are likely to yield further scientific evidence on its bone-protective effects and safety. Keywords: Radix Dipsaci, Diabetic osteoporosis, Rosiglitazone.

Keratin 7 Is a Constituent of the Keratin Network in Mouse Pancreatic Islets and Is Upregulated in Experimental Diabetes

Keratin (K) 7 is an intermediate filament protein expressed in ducts and glands of simple epithelial organs and in urothelial tissues. In the pancreas, K7 is expressed in exocrine ducts, and apico-laterally in acinar cells. Here, we report K7 expression with K8 and K18 in the endocrine islets of Langerhans in mice. K7 filament formation in islet and MIN6 β-cells is dependent on the presence and levels of K18. K18-knockout (K18‒/‒) mice have undetectable islet K7 and K8 proteins, while K7 and K18 are downregulated in K8‒/‒ islets. K7, akin to F-actin, is concentrated at the apical vertex of β-cells in wild-type mice and along the lateral membrane, in addition to forming a fine cytoplasmic network. In K8‒/‒ β-cells, apical K7 remains, but lateral keratin bundles are displaced and cytoplasmic filaments are scarce. Islet K7, rather than K8, is increased in K18 over-expressing mice and the K18-R90C mutation disrupts K7 filaments in mouse β-cells and in MIN6 cells. Notably, islet K7 filament networks significantly increase and expand in the perinuclear regions when examined in the streptozotocin diabetes model. Hence, K7 represents a significant component of the murine islet keratin network and becomes markedly upregulated during experimental diabetes.

Age features of morphological changes of vessels of testicular hemomicrocirculatory flow in streptozotocin diabetes mellitus

Medico-social problem of diabetes is caused by early disability and mortality of patients due to specific complications of micro- and macroangiopathies. Therefore, the aim of our study was to establish morphological changes in vessels of the hemomicrocirculatory flow of the testes of immature rats with experimental streptozotocin diabetes mellitus (SDM). The material for the study were the testicles of 20 two-month-old immature (weighing 65-95 g) white outbred male rats, which were divided equally into 2 groups: experimental and control ones. SDM in animals of the experimental group was simulated by a single intraperitoneal injection of streptozotocin (dissolved in 0.1 M citrate buffer solution with a pH of 4.5) at a dose of 7 mg per 100 g of mass. The control group of animals received intraperitoneally an equivalent dose of 0.1 M citrate buffer. Histological, electron microscopic, biochemical, morphometric and statistical research methods were used. It was found that in the early stages of SDM (14th day) on the background of hyperglycemia in the hemomicrocirculatory flow of the testes there is a spasm of the vessels of the afferent link, which is confirmed by a decrease in the area of arterioles lumen and an increase in their VI. On the 56th day of SDM, on the background of elevated levels of glucose and glycosylated hemoglobin in the links of the hemorrhagic circulatory flow of the testes there are initial signs of diabetic microangiopathy, manifested by: hemorheological disorders in micro-hemo-vessels (erythrocyte sludges, adhesion of erythrocytes and platelets, microclasmatosis), decreased capacity of arterioles and capillaries (increase in VI, respectively by 1.2 and 1.9 times), microclasmatosis, thickening and proliferation of the basement membrane of capillaries. Thus, on the 56th day of SDM in the hemomicrocirculatory flow of the testes, the development of diabetic microangiopathy is observed, which leads to the disruption of the blood-testis barrier, and as a consequence, to a violation of spermatogenesis.

Treatment of Diabetic Neuropathy with A Novel PAR1-Targeting Molecule

Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p < 0.001), and had hypoalgesia (p < 0.05), slow conduction velocity (p < 0.0001) and reduced skin innervation (p < 0.0001). Treatment with PARIN5 significantly improved rotarod performance (p < 0.05), normalized hypoalgesia (p < 0.05), attenuated slowing of nerve conduction velocity (p < 0.05) and improved skin innervation (p <0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.