Abstract
Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.
Highlights
Arterial hypertension is considered a major risk factor in the development of several cardiovascular diseases, such as myocardial infarction and stroke [1–3], which together were responsible for 15 million deaths in 2015 [4]
InInthe study, we we carried out the evaluation of 19 natural products, which thepresent present study, carried outpharmacological the pharmacological evaluation of 19 natural products, we had previously isolated from plants widely used in Mexican traditional medicine, in the search which we had previously isolated from 10 plants widely used in Mexican traditional medicine, in the ofsearch leads of that could becould used be to develop new therapeutic agents to treat to cardiovascular diseases
ATP pathways in endothelial cells importantly contributes to vasorelaxation, we investigated whether the presence of endothelium importantly contributes to vasorelaxation, we investigated whether the presence of endothelium and and activation these biochemical pathwayswere wereinvolved involvedin in the the vasorelaxant activation of of these biochemical pathways vasorelaxant effect effect elicited elicited by by compounds
Summary
Arterial hypertension is considered a major risk factor in the development of several cardiovascular diseases, such as myocardial infarction and stroke [1–3], which together were responsible for 15 million deaths in 2015 [4]. Several drugs are currently used in the treatment of high blood pressure, less than a third of the hypertension cases are successfully treated [5–8]. It has been broadly demonstrated that endothelial dysfunction, characterized by a diminished availability of endothelial relaxing factors, significantly contributes to the development of hypertension. Molecules 2018, 23, x FOR PEER REVIEW and other cardiovascular diseases [9–11]. Reduced release of the gasotransmitters gasotransmitters NO andimpaired. H2S results in an of impaired regulation of the vascular tone and H2 S results in an regulation the vascular tone [12–14]
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