Bio-guided Fractionation of the Ethanolic Extract from Leaves of Trema orientalis Blume (Cannabaceae), a Presumed Antihypertensive Plant from Congo-Brazzaville

Hypertension is a risk factor for cardiovascular disease, which is currently a real public health problem. This disease affects about one billion people worldwide and is responsible for more than 70% of cardiovascular related deaths. Recently, the World Health Organization reported that of the hypertensive cases detected in Congo, only 7% were controlled. Today, there is no lifetime treatment and existing drugs are less accessible by the African population. To treat the disease, the Congolese population uses more the medicinal plants. However, the majority of compounds responsible for the biological activity of these plants are not known. In order to bring out Congolese plants with antihypertensive properties, we focus our interest on Trema orientalis Blume (Canabaceae). An ethanolic extract of the leaves of Trema orientalis was prepared after successive depletion of the organic solvents. Thereafter, a bio-guided fractionation on silica gel of the ethanol extract was carried out. Fractionation monitoring was done by TLC and the results of vasodilating activity measured. The fractions exhibiting the best biological activity allowed a second fractionation process to obtain five fractions which are characteristic of polyphenols, in particular flavonoids, and which exhibited good vasodilating activity on the isolated aorta of rats. Our future work will focus on the identification of these biologically active compounds.

ENDOTHELIAL PROTECTIVE ACTIVITY OF 2,6-DIISOBORNYL-4-METHYLPHENOL IN A MODEL OF MYOCARDIAL ISCHEMIA/REPERFUSION IN RATS

Objective: Our research focuses on the endothelial protective effects of 2,6-diisobornyl-4-methylphenol. Its effect was revealed while studying rats experiencing myocardial ischemia/reperfusion. The research results demonstrated that there are significant disturbances in the vascular endothelium manifested by a decrease in the vasodilating activity and antiplatelet properties of 2,6-diisobornyl-4-methylphenol. Methods: We designed our own model of myocardial ischemia/reperfusion and applied it to 52 adult outbred Wistar males. We employed some methods of hemostasiological research such as thromboelastography to determine the antiplatelet activity of the vascular wall, G. Born nephelometric method to study platelet aggregation, phase contrast microscopy to count platelet counts in blood plasma, measurement of intra-arterial pressure to study the endothelial vasodilating function, and calculated the endothelial dysfunction coefficient in rats. Results: Preventive intragastric injection of 2,6-diisobornyl-4-methylphenol (100 mg/kg, 3 days before and 5 days after reproducing the myocardial ischemia/reperfusion model) increased the antiplatelet activity of the vascular endothelium in rats by 37% compared to the endothelium of the abdominal aorta segment of untreated animals. Moreover, 2,6-diisobornyl-4-methylphenol decreased the endothelial dysfunction coefficient by 43% in comparison with the value in the control group. Conclusion: 2,6-diisobornyl-4-methylphenol has an endothelial protective effect proved by its ability to increase antiplatelet properties of the endothelium and decrease the endothelial dysfunction coefficient. The revealed endothelial protective properties of 2,6-diisobornyl-4-methylphenol can be regarded as one of the potential mechanisms of cardioprotective activity of the drug.

Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs.

CORRECTION OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH TERMINAL RENAL INSUFFICIENCY

The problem of development of endothelial disfunction in patients with end-stage renal failure and possibilities of its correction in extracorporal and medical methods is discussed.In research took part 60 patients with chronic kidney disease stage V by K/DOQI, which was evaluated vasomotor endothelial function in samples with reactive hyperemia and nitroglycerin, with simultaneous detection of the concentration of endothelin-1. The study confirmed the expressed changes of indicators vasodilating activity of the vascular wall and raising of endothelin-1 level in patients of this group. Effective method of correction of endothelial disfunction in patients with terminal renal insufficiency was early initiation of haemodyalisis therapy in combination with ACE inhibitors pharmacotherapy.

Effects of freeze-dried red wine on cardiac function and ECG of the Langendorff-perfused rat heart

The effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects.

Benefits of vasodilating beta-adrenoblockers for arterial hypertension treatment

Antihypertensive medications of the same class could differ by their pharmacodynamic parameters, which substantially affects the longterm treatment results. Nebivolol is one of the modern, highly selective β-adrenoblockers (β-AB). It is characterised not only by high β1-selectivity, but also by additional vasodilating activity, due to increased nitric oxide synthesis and, hence, beneficial metabolic effects. The results of the original studies and the external evidence demonstrate metabolic neutrality of nebivolol, absence of substantial changes in thyroid hormone levels, and improvement in heart rate variability, electrophysiological myocardial parameters, QT interval duration, and cerebral perfusion. Nebivolol is effective and safe even in higher-risk patients with metabolic syndrome and Type 2 diabetes mellitus.