RESUMO
As an effective medicine for jaundice in traditional Chinese medicine, Cucumis melo L. has been widely used in China. However, its effect on vascular function is still unclear. In this study, we extracted the compounds of Cucumis melo L., and the major ingredients were identified as cucurbitacins (CuEC, cucurbitacins extracted from Cucumis melo L.), especially cucurbitacin B. We replicated the toxicity in mice by intraperitoneal injection of a high dose of CuEC (2 mg/kg) and demonstrated that the cause of death was CuEC-induced impairment of the endothelial barrier and, thus, increased vascular permeability via decreasing VE-cadherin conjunction. The administration of low doses of CuEC (1 mg/kg) led to a decline in systolic blood pressure (SBP) without causing toxicity in mice. More importantly, CuEC dramatically suppressed angiotensin II (Ang II)-induced SBP increase. Further studies demonstrated that CuEC facilitated acetylcholine-mediated vasodilation in mesenteric arteries of mice. In vitro studies showed that CuEC induced vasodilation in a dose-dependent manner in mesenteric arteries of both mice and rats. Pretreatment with CuEC inhibited phenylephrine-mediated vasoconstriction. In summary, a moderate dose of CuEC reduced SBP by improving blood vessel tension. Therefore, our study provides new experimental evidence for developing new antihypertensive drugs.
