Jervine,promoveratrineA（proA），和promoveratrineB（proB）是Verratum生物碱，存在于从Verrumlobelianum获得的一些补救措施中，如Veratrumaqua。本文报道了一项单中心飞行员心脏毒性机制研究。proA,和proB在案例系列中。通过分子动力学模拟研究了分子方面，与心脏钠通道NaV1.5的分子对接，以及基于机器学习的结构-活性关系建模。采用HPLC-MS/MS法结合临床事件对患者进行心脏毒性分析。Jervine显示出最高的对接分数（-10.8kcal/mol），logP值（4.188），pKa值(9.64)与proA和proB比较。此外，该化合物的特征在于计算的最低IC50。总的来说,所有三种分析的生物碱均显示出对NaV1.5的亲和力,很可能导致心脏毒性作用.veratrumaqua中毒7例的临床数据证实了分子建模的结果。患者表现出恶心，肌肉无力,心动过缓,动脉低血压.描述了血液和尿液中生物碱浓度与患者病情严重程度之间的关系。这些实验,虽然主要，确认了Jervine,proA,proB通过NaV1.5抑制促进心脏毒性。
Jervine, protoveratrine A (proA), and protoveratrine B (proB) are Veratrum alkaloids that are presented in some remedies obtained from Veratrum lobelianum, such as Veratrum aqua. This paper reports on a single-center pilot cardiotoxic mechanism
study of jervine, proA, and proB in case series. The molecular aspects were studied via molecular dynamic simulation, molecular docking with cardiac sodium channel NaV1.5, and machine learning-based structure-activity relationship modeling. HPLC-MS/MS method in combination with clinical events were used to analyze Veratrum alkaloid cardiotoxicity in patients. Jervine demonstrates the highest docking score (-10.8 kcal/mol), logP value (4.188), and pKa value (9.64) compared with proA and proB. Also, this compound is characterized by the lowest calculated IC50. In general, all three analyzed alkaloids show the affinity to NaV1.5 that highly likely results in cardiotoxic action. The clinical data of seven cases of intoxication by Veratrum aqua confirms the results of molecular modeling. Patients exhibited nausea, muscle weakness, bradycardia, and arterial hypotension. The association between alkaloid concentrations in blood and urine and severity of patient condition is described. These experiments, while primary, confirmed that jervine, proA, and proB contribute to cardiotoxicity by NaV1.5 inhibition.
