Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Ciudad Universitaria, San Nicolás de los Garza, CP 66451 Nuevo León, Mexico.
Molecules. 2018 Jun 18;23(6):1474. doi: 10.3390/molecules23061474.
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: -dihydroguaiaretic acid [half maximal effective concentration (EC), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC, 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 (K) 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 -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 -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.
动脉高血压是心血管疾病发展的主要危险因素之一。因此，寻找治疗高血压的新药非常重要。在这项研究中，我们对 10 种墨西哥传统医学中使用的植物中分离得到的 19 种化合物（三萜、二萜、倍半萜、木脂素和类黄酮）进行了筛选，以确定它们是否能引起血管平滑肌松弛，从而可能成为新的抗高血压药物候选物。这些化合物的血管舒张活性在离体大鼠主动脉实验中进行了评估，评估结果表明，有三种化合物诱导了显著的血管舒张作用：-二氢愈创木酸[半数有效浓度（EC）为 49.9 ± 11.2 µM；最大效应（Emax）为 99.8 ± 2.7%]；齐墩果酸（EC 为 108.9 ± 6.7 µM；Emax 为 96.4 ± 4.2%）和 5,8,4′-三羟基-3,7-二甲氧基黄酮[EC 为 122.3 ± 7.6 µM；Emax 为 99.5 ± 5.4%]。随后，评估了这些化合物血管舒张活性所涉及的一氧化氮/环鸟苷单磷酸（cGMP）和 H₂S/三磷酸腺苷敏感性钾通道（K）途径。该分析得出的结果表明，这两种途径的激活都有助于齐墩果酸的血管舒张作用。另一方面，-二氢愈创木酸和 5,8,4′-三羟基-3,7-二甲氧基黄酮的血管舒张作用部分涉及一氧化氮/cGMP 途径的刺激。然而，这些化合物还表现出重要的内皮非依赖性血管舒张作用，其作用机制仍有待阐明。这项研究表明，-二氢愈创木酸、齐墩果酸和 5,8,4′-三羟基-3,7-二甲氧基黄酮可作为合成新型衍生物的先导化合物，这些衍生物具有更高的效力，可开发用于预防和治疗心血管疾病。
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