Nghiên cứu độc tính và tác dụng hạ glucose máu của viên andiabet trên thực nghiệm tt tiếng anh

1 INTRODUCTION Type diabetes mellitus (T2D) is a metabolic disorder with complex mechanisms and pathophysiological abnormalities It is extremely hard to reverse T2D disease state with monotherapy Thus combination therapy is becoming a promising alternative choice in clinical practice by designing drug combinations or compound drugs to interact with multiple targets and achive synergitic treatment effect For example, traditional Vietnamese medicines are attracting more attentions for their efficacy and less frequent side effects for treating T2D Lagerstroemia speciosa (L.) Pers; Gynostemma pentaphyllum (Thunb.) Makino; Anemarrhenae Aspheloides (Bunge) has been reported to alleviate hyperglycemia and hyperlipemia in many preclinical and clinical studies and have been combined into the soft form of Vinabetes However, Vinabetes has only been extracted in laboratory and there are no adequate pharmacological studies Andiabet is a compound of Vietnamese herbal medicines composition above The aim of this study was to investigate the toxicity and the hypoglycemic effect of Andiabet in experimental animals with the following objectives: Determine of acute toxicity and longterm toxicity by Andiabet Evaluate the hypoglycemic effect and several hypoglycemic mechanisms of Andiabet tablets in experiment Chapter OVERVIEW 1.1 OVERVIEW ABOUT THE DIABETES MELLITUS 1.1.1 Definition, classification, diagnostic criteria for diabetes and pathogenetic mechanism of diabetes type 1.1.1.1 Definition “Diabetes is a metabolic disorder characterized by hyperglycemia, the result of a deficiency of insulin secretion; impaired functioning of insulin; or both Chronic hyperglycemia is often associated with damage, disorders and impaired function of many organs, especially the eyes, kidneys, nerves, heart and blood vessels.” 1.1.1.2 Classification: Diabetes is divided into types: diabetes type 1, type 2, diabetes pregnancy and special types In which, type and type diabetes is most common 1.1.1.3 Diagnostic criteria for diabetes Four diagnostic tests for diabetes are currently recommended, including measurement of fasting plasma glucose; 2-hour (2-h) postload plasma glucose after a 75 g oral glucose tolerance test (OGTT); HbA1c; and a random blood glucose in the presence of signs and symptoms of diabetes People with fasting plasma glucose values of ≥ 7.0 mmol/L (126 mg/dl), 2-h post-load plasma glucose ≥ 11.1 mmol/L (200 mg/dl), HbA1c ≥ 6.5% (48 mmol/mol); or a random blood glucose ≥ 11.1 mmol/L (200 mg/dl) in the presence of signs and symptoms are considered to have diabetes 1.1.1.4 Pathogenetic mechanism of diabetes type Insulin resistance in peripheral tissues and insulin secretion disorders are two important and related closely factors in the pathogenesis of type diabetes, which usually occurs before the clinical manifestations of diabetes (from the pre-diabetes phase) However, in patients with type diabetes who are not overweight, the manifestation of insulin secretion is the opposite, whereas in type diabetes patients with obesity, insulin resistance is the main condition Genetic and environmental factors play a role in promoting disease development and development 1.2 GROUPS OF MEDICINE TREATMENT FOR DIABETES Currently, in addition to lifestyle adjustment (diet and exercise), drugs should be used to treat of type diabetes The drugs for treatment of type diabetes focus on the following main groups: 1.2.1 Drugs stimulate insulin secretion include: KATP channel inhibitors are: sulfonylurea and meglitinide The incretin modulators are: GLP-1 analogues: Exenatid, Liraglutid, Lixisenatid and DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin 1.2.2 Drugs reduce insulin resistance include: metformin and thiazolidinedion: pioglitazon 1.2.3 Drugs reduce/slow absorption of glucid: drugs a-glucosidase inhibitors include: acarbose (Precose, Glucobay) and miglitol (Glyset) 1.2.4 Drugs increase renal glucose excretion: SGLT2 inhibitors are: Dapagliflozin, Canagliflozin and Empagliflozin 1.3 SEVERAL DIABETIC RESEARCH METHODS IN EXPERIMENTANT 1.3.1 The invivo research model 1.3.1.1 Models of type diabetes: Spontaneous type diabetes (T1D) models and secondary T1D models induced by chemicals, removing pancreas or virus 1.3.1.2 Models of type diabetes: Obese and non-obese spontaneous T2D rodents models Secondary T2D models: induced by chemicals or a high-fat diet combined with low-dose STZ and by genetic modification 1.3.1.3 Several methods to evaluate hypoglycemic effect in invivo: Assessing the ability of the drug on glucose tolerance test, polysaccharide absorption Assessing the drug’s effect of increasing insulin sensitivity to the target tissue via the technique "Hyperinsulinemic - euglycemic clamp test" 1.3.2 The invitro research model The invitro research model can be divided into two categories: assessing the of drug’s effect on organs, isolated cells and on enzymes involved glucose homeostasis 1.4 OVERVIEW COMPONENTS OF ANDIABET AND RESEARCHS RELATED TO ANDIABET Lagerstroemia speciosa (L.) Pers; Gynostemma pentaphyllum (Thunb.)Makino; Anemarrhenae aspheloides (Bunge) was estimated for hypoglycemic virtue in many preclinical and clinical studies and have been combined into the soft form of Vinabetes Vinabetes with a 1,5:1,5:1 weight ratio of the three herbal composition, similar to Andiabet was performed acute toxicity test and LD50 dose was 42.98 g/kg mice Vinabetes has also been studied for long term toxicity test in rabbits for weeks at doses of 1.8 g/kg/day and 3.6 g/kg/day Vinabetes at the doses for 4.5g/kg and 9g/kg for consecutive weeks in normal mice displayed significantly reducing blood glucose levels (by 34 % and 44 %, respectively) compared to the control (p