Propriétés thérapeutiques de l’extrait aqueux des écorces du tronc de Erythrina senegalensis DC (Fabaceae) sur un modèle de comorbidité hypertension artérielle-diabète et quelques complications chez le rat

Abstract

Hypertension and diabetes are frequently linked in the general population. These conditions are major risk factors for micro and macroangiopathic complications. Their management is based on hygienic and dietary measures and a combination of therapies that are difficult to comply with. Thanks to the many bioactive metabolites they contain, medicinal plants have demonstrated their potential in the treatment of various chronic pathologies. The aim of this thesis was to evaluate the antihypertensive and antidiabetic activity of the aqueous extract of the trunk bark of Erythrina senegalensis DC (Fabaceae) in a comorbidity model. For the in vivo study, aqueous extract of E. senegalensis at doses of 50, 100 and 300 mg/kg was administered to normoglycaemic rats. Blood glucose monitoring and oral glucose tolerance test (OGTT) to glucose, maltose and starch were performed. Normal rats were made hypertensive by daily oral administration, for 42 days, of 15% sucrose followed by 40° alcohol at doses of 1.5 g/kg and 5 g/kg respectively. Hypertensive rats were made diabetic by a single intravenous injection of streptozotocin (STZ) solution at a dose of 35 mg/kg. Two weeks later, the animals with blood glucose levels greater than or equal to 126 mg/kg were considered to be diabetic hypertensives and divided into two batches, one of which (the first) was treated directly for four weeks and the other batch (the second), which continued to receive the alcohol sucrose solution, was left untreated to set up complications. The first batch consisted of 4 groups of 5 rats, including a diabetic hypertensive group (THD) receiving distilled water at 10 mL/kg, a positive control (TMN) receiving metformin (200 mg/kg) and nifedipine (10 mg/kg), and two test groups receiving the extract at doses of 100 and 200 mg/kg respectively. A group of normal rats (TN) receiving distilled water at 10 mL/kg was added. Two weeks (2) later, the rats of the second batch were divided into 5 groups of 5 animals each, including a THD group (receiving distilled water at 10 mL/kg), TMN (receiving metformin and nifedipine at 200 and 10 mg/kg, respectively), and three groups receiving the extract at doses of 50, 100 and 300 mg/kg respectively. A group of normal rats (TN receiving distilled water at 10 mL/kg) was added. During each experimental period, blood glucose levels were measured at the end of each week and urine was collected. Behavioural tests were also carried out before and after treatment in the second batch of rats. At the end of each experimental period, blood glucose levels and some haemodynamic parameters were assessed. The animals were sacrificed, the blood centrifuged and the supernatant collected for the determination of some serum biochemical parameters. Organs such as the pancreas, aorta, heart, liver, kidney, testis, epididymis, prostate, seminal vesicle and brain were removed and weighed. The tail of the epididymis was used for the spermogram. Part of each organ was homogenised in a specific buffer for the determination of some tissue parameters and the other part was fixed in 4% formalin for subsequent histological analysis. In vitro tests were carried out for hypoglycaemic activity (glucose chelation, glucose absorption by brewer's yeast) and antioxidant activity (Fe3+ chelation, inhibition of ABTS and DPPH radicals). Qualitative and quantitative phytochemistry of the E. senegalensis extract was carried out. In normoglycaemic rats, E. senegalensis extract inhibited the hyperglycaemic peak and accelerated the fall in blood glucose levels during blood glucose monitoring and the OGTT test. Co-morbidity of arterial hypertension and diabetes led to a significant increase in blood pressure, blood sugar levels, transaminase activity, total cholesterol, triglycerides, bilirubin, creatinine, uric acid and urea. There was also a significant reduction in insulin, fructose and testosterone levels, as well as in sperm quality and number. The extract significantly lowered blood pressure and blood sugar levels. At different doses, the extract improved the lipid profile, transaminase activity, bilirubin, creatinine, uric acid, urea, calcium, sodium, magnesium, potassium, phosphorus and chlorine ions, insulin, testosterone, fructose, motivation and sexual performance. The spermogram revealed a significant increase in sperm count, viability and mobility. E. senegalensis also improved anxiety and depression and regulated the metabolism of certain neurotransmitters. The extract maintained the oxidative status and structural integrity of the heart, aorta, liver, kidneys, brain androgen-dependent organs close to that of normal controls. In vitro, E. senegalensis stimulated glucose uptake by yeast, chelated glucose, inhibited haemoglobin glycation and alpha- amylase and alpha-glucosidase activity. The extract inhibited protein denaturation, proteinase activity, ABTS and DPPH radicals. Phytochemical analysis revealed the presence of several classes of compounds, with an abundance of polyphenols. These results show that the antihypertensive and antidiabetic properties of the aqueous extract of E. senegalensis are capable of preventing and improving complications in hypertensive diabetic rats. These properties would justify, at least in part, its empirical use in the treatment of arterial hypertension and diabetes.