Endothelium-independent and endothelium-dependent vasorelaxation by a dichloromethane fraction from <i>Anogeissus leiocarpus</i> (dc) <i>guill</i>. Et <i>Perr. (combretaceae)</i>: possible involvement of cyclic nucleotide phosphodiesterase inhibition

Abstract

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.

Safety evaluation of Bon-santé cleanser ® polyherbal in male Wistar rats: Further investigations on androgenic and toxicological profile

“…Interestingly, both folkloric medicine uses and several proposed properties of the potentials of the extracts of the aforementioned medicinal plantsincluding their phytoconstituents have been verified scientifically in rodents. 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 For instance, M . acuminate (G .…”

Effect of Anogeissus leiocarpus Guill and Perr Leaf on Hyperglycaemia and Associated Dyslipidaemia in Alloxan-induced Diabetic Rats

“…These results are in line with the report of other workers that A. leiocarpus leaves contain high bioactive substances, notably antioxidants such as ellagic, gallic and gentisic acids, derivatives of gallic and ellagic acids and several flavonoids (derivatives of quercetin and kaempferol which are reported to have hypoglycaemic action. 5,10,11 It has also been shown that plant nutrients play protective roles against oxidative stress in diabetic rats. 15,16 The ability of the A. leiocarpus ethanolic leaf extract to protect the rats against oxidative stress could be attributed to its hypoglycaemic principles.…”

Long-lasting endothelium-dependent relaxation of isolated arteries caused by an extract from the bark of Combretum leprosum

“…19 , 20 In fact, such mechanism has been recently proposed for the relaxant effect of a dichloromethane fraction from Anogeissus leiocarpus , a combretaceae. 21 …”

“…19 , 20 Na verdade, tal mecanismo foi proposto recentemente para o efeito relaxante de uma fração diclorometano de Anogeissus leiocarpus , um combretáceo. 21 …”