Ethyl Acetate Fraction from Leandra dasytricha (A. Gray) Cong. Leaves Promotes Vasodilatation and Reduces Blood Pressure in Normotensive and Hypertensive Rats.

Leandra dasytricha (A. Gray) Cong. is widely distributed in the south of Brazil and is commonly used for cardiovascular and kidney ailments. For this study, we used male Wistar normotensive rats (NTRs) and spontaneously hypertensive rats (SHRs) to verify the effects of the ethyl acetate fraction (EAF) obtained from L. dasytricha leaves on isolated aorta relaxation and in the arterial blood pressure. The EAF was analyzed by LC-DAD-MS, and several components were annotated, including hydrolysable tannins, triterpenes, and O- and C-glycosylated dihydrochalcones, such as the most intense ion peak relative to C-hexosyl phloretin (nothofagin; compound number 13). The EAF caused a concentration and endothelium-dependent relaxation of the aorta in both NTRs and SHRs. This effect was abolished in the endothelium-denuded aorta. L-NAME, a nonselective nitric oxide synthase inhibitor, and ODQ, a soluble guanylate cyclase inhibitor, entirely blocked the EAF-induced relaxation. The presence of a muscarinic receptor antagonist or a cyclooxygenase inhibitor did not alter the EAF's effectiveness in relaxing the aorta. The preincubation with tetraethylammonium, a Ca2+-activated K+ channel blocker, and with 4-aminopyridine, a voltage-dependent K+ channel blocker, significantly interfered with the EAF's relaxation. However, the incubation with glibenclamide, an ATP-sensitive K+ channel blocker, and barium chloride, an inward-rectifier K+ channel blocker, did not interfere with the EAF-induced relaxation. The EAF treatment also caused a dose-dependent decrease in the mean arterial pressure, systolic arterial pressure, and diastolic arterial pressure of both NTRs and SHRs, without significantly interfering with heart rate values. In conclusion, this study demonstrated the EAF-induced vasorelaxant and hypotensive actions, primarily dependent on the endothelium function and mainly with the participation of the nitric oxide and Ca2+-activated and voltage-dependent K+ channels.

Clinical safety of lauric acid for cattle and its in vitro and in vivo efficacy against Rhipicephalus microplus.

The aim of the present study was to test the in vitro acaricidal activity of saturated fatty acids (hexanoic, octanoic, decanoic, lauric, myristic, palmitic, octadecanoic, eicosanoic, docosanoic and tetracosanoic) against Rhipicephalus microplus and select a candidate compound for the subsequent determination of its clinical safety for mice and bovines as well as its in vivo efficacy (ethical clearance number 507/2013). None of the compounds exhibited in vitro larvicidal effectiveness, but acaricidal effectiveness was greater than 95 % in the adult immersion test at 40 mg/ml (hexanoic, octanoic, decanoic, lauric, myristic, palmitic and eicosanoic acids). After a second AIT evaluation of serial concentrations of the fatty acids, lauric and myristic acids were selected for the safety and in vivo efficacy assays. No adverse effect was found in the local lymph node assay in mice treated with lauric or myristic acid. Moreover, no clinical signs of systemic poisoning or dermatological, hematological or biochemical abnormalities were found in cattle after the topical application of 1 % lauric acid. In the dose determination test, the 1% solution of this compound exhibited 86% efficacy in cattle naturally infested by a field population of Rhipicephalus microplus susceptible to all chemical groups, except synthetic pyrethroids. The efficacy of 1 % lauric acid was 53.4 % in the dose confirmation test performed on another herd with a field R. microplus population resistant to all chemical groups of acaricides. In conclusion, fatty acids are potential bioactive compounds for the control of R. microplus. Topically applied lauric acid (C12) exhibits in vivo acaricide activity against adults, nymphs and larvae of R. (B) microplus and is safe for cattle.