1 The possible roles of the L-arginine-NO pathway and of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in regulating the prejunctional release of noradrenaline and neurogenic vasoconstriction were investigated in the perfused rat tail artery. 2 In the presence of Nw-nitro-L-arginine methyl ester (L-NAME; 30 JM), an inhibitor of NO formation, the vasoconstrictor responses to perivascular nerve stimulation (24 pulses at 0.4 Hz, 0.3 ms, 200 mA) and to exogenous noradrenaline (1 JM) were significantly enhanced, whereas the stimulation-evoked tritium overflow from [3H]-noradrenaline preloaded arteries was not modified. The vasoconstriction enhancing effect of L-NAME was prevented by L-arginine (1 mM) but not D-arginine (1 mM) and was abolished by removal of the endothelium. 3 The NO donor, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1; 0.1-30JAM), and the cyclic GMP phosphodiesterase inhibitor, zaprinast (0.1-30 JM) both induced a concentration-dependent inhihition of the electrical field stimulation-induced vasoconstriction, while atrial natriuretic peptide (ANP; 100nM) produced only a slight decrease of the vasoconstrictor response. Methylene blue (3JM), a known inhibitor of soluble guanylate cyclase increased the electrical field stimulation-induced vasoconstriction. SIN-1 and methylene blue when administered simultaneously, antagonized each others effect. None of the compounds tested (SIN-1, zaprinast, ANP or methylene blue) had any significant effect on the stimulation-evoked [3H]-noradrenaline overflow. 4 8-Bromo-cyclic GMP, a potent activator of cyclic GMP-dependent protein kinase, markedly and concentration-dependently (3-300 JM) increased [3H]-noradrenaline overflow but decreased field stimulation-induced vasoconstriction. Dibutyryl-cyclic GMP (100 JM), a weak activator of cyclic GMPdependent protein kinase, affected neither the pre-nor the postjunctional response to electrical field stimulation. 5These data show that an NO-like substance of endothelial origin, derived from L-arginine, attenuates vasoconstriction in the rat tail artery, whether neurally-induced or evoked by exogenous noradrenaline. Since noradrenaline release was unaltered by compounds modifying NO production, this NO-like compound acted through a postjunctional mechanism. The lack of prejunctional effects of both soluble and membrane-associated guanylate cyclase activators, despite a large effect of 8-bromo-cyclic GMP, suggests that endogenous cyclic GMP production, if present in sympathetic nerves, may not be involved in the regulation of noradrenaline release in the rat tail artery.
The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD 50 ) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1-10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC 50 values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1-4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10 -5 M), and not by L-NAME (310 -4 M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.
A b s t r a c tSickle cell disease is a major public health problem. It is the first genetic disease in the world. FACA syrup offers an alternative treatment. It is a dry powder preparation of two components, the roots barks of Zanthoxylum zanthoxyloides Lam. (Rutaceae) Zepernick, Timler and Calotropis procera.Ait. R.B.r. (Asclepiadaceae). The product was developed at Institute for Research in Health Sciences (IRSS) from a traditional recipe used in Burkina Faso for treatment of sickle cell crises. This study aimed to establish physical-chemical, pharmaco technical and microbiological control parameters essential for the standardization of the phytomedicine. This valuation concerned specifications of moisture content, pH, the fingerprint by thin layer chromatography, pesticide residues, heavy metal content, microbial quality, and total ash. These charcteristics were determined by the methods prescribed by the World Health Organization (1998) and the European Pharmacopoeia 6th edition. The results have shown that dry syrups and reconstituted syrups were sweet, slightly spicy with a bitter after taste, a white room color and a faint odor. The density at the preparation was 0.985 and the pH was 5.93. After 2 months of storage in the laboratory, the organoleptic parameters of the reconstituted syrups have not changed. They were mold free, the density remained around 1 and the pH between 5 and 4. These parameters have shown that the quality of plants powders and this medicine comply with the recommendations of the European pharmacopoeia. Faca syrup may contribute to the better management of sickle cell disease in children.
Many traditional medicinal herbs from Burkina Faso are used to treat arterial hypertension (HTA). Among them, Anogeissus leiocarpus (A. Leiocarpus) which is well known and widely used in Burkina traditional medicine. Herein we assess the effects of dichloromethane fraction from A. leiocarpus stem bark (ALF), selected as the most active on cyclic nucleotide phosphodiesterases (PDEs) and characterized its specificity towards purified vascular PDE1 to PDE5 isoenzymes and study its effects on a vascular model. ALF potently and preferentially inhibits (IC 50 =1.6 ± 0.6 µg/mL) the calmodulindependent phosphodiesterase PDE1, being mainly present in vascular smooth muscle and preferentially hydrolyses cGMP. In the same range (IC 50 =2.8 ±0.2 µg/ml) ALF inhibits PDE2, a cGMP-activated enzyme that is only present in endothelial cells and hydrolyses both cAMP and cGMP. PDE5, which specifically hydrolyses cGMP and which mainly contributes to cGMP hydrolysis is also potently inhibited by ALF (IC 50 =7.6±3.5 µg/ml). The potencies of ALF on cAMP hydrolyzing isoenzymes was lesser, being more effective on PDE4 (IC 50 = 17.6±3.5 µg/ml) than on PDE3 (60.9 ± 1.8 µg/ml). Since the major effect of ALF were against cGMP hydrolysis and since cGMP is implicated in endothelium-dependent relaxation, the endotheliumdependent vasorelaxation was studied on isolated porcine coronary arteries rings pre-contracted with U46619. The endothelium-dependent vasorelaxation is significantly inhibited by N ω -nitro-L-arginine (LNA 300 µmol/L, an inhibitor of endothelial NO synthase), but not affected by charybdotoxin (CTX, 100nM) plus apamin (APA, 100nM) (two inhibitors of EDHF-mediated responses). The combination of 4-aminopyridine (4-AP, 1 mmol/L, inhibitor of voltage-dependent potassium channels, K v ) plus baryum (Ba 2+ , 30 µmol/L, inhibitor of the potassium channels with entering correction, K ir ) plus ouabain (3 µmol/L, inhibitor of ATPase Na + /K + channels) partially inhibits endothelium-independent vasorelaxant effect. This endothelium-independent relaxant effect was also sensitive to combination of 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one (ODQ, 10 µM, soluble guanylyl cyclase inhibitor) and N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H89, 100 nM, Protein Kinase A inhibitor). Taken together, these results indicate that ALF is a powerful vasodilator modulated by the formation of NO from endothelium, but also act by directly relaxing the vascular smooth muscle cells, by inhibiting cGMP hydrolyzing PDEs (PDE1, PDE2 and PDE5) and to a lesser extend on cAMP degradation (PDE3 and PDE4), cAMP and cGMP being second messengers involved in vascular relaxation.
Diabetes mellitus is a socially significant disease characterized by chronic hyperglycemia and metabolic disorders of proteins, carbohydrates, and lipids due to reduced function of insulin. Medicinal plants, rich in bioactive components that promote prevention and treatment, are inexpensive and no side effects. Apium graveolens, Cleome gynandra, and Hibiscus sabdariffa from Burkina Faso were investigated for their phytochemical profile and antioxidant activities. The high-performance thin-layer chromatography profile revealed flavonoids, tannins, and sterols in these herbaceous. The Hibiscus sabdariffa methanolic extract exhibited the highest total phenolic (138.4 ± 0.5 mg GAE/g DW) and flavonoid (52.8 ± 0.6 mg RuE/g DW) contents comparatively to Cleome gynandra and Apium graveolens. Hibiscus sabdariffa methanolic extract also presented the highest antioxidant activity (IC 50 = 0.31 ± 0.002 mg/mL) using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay. A high correlation between flavonoid contents and hydrophilic antioxidant activities (r = 0.99) was observed, indicating that flavonoids contribute significatively to these herbaceous antioxidant properties.Apium graveolens, Cleome gynandra, and Hibiscus sabdariffa constitute a natural source of phenolic compounds that could be exploited in diabetes mellitus management.
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