{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T01:29:06Z","timestamp":1769822946525,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["75-15-2022-305"],"award-info":[{"award-number":["75-15-2022-305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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\u2013activity 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 (\u221210.8 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.<\/jats:p>","DOI":"10.3390\/toxins14070490","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T01:53:22Z","timestamp":1658109202000},"page":"490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insights into the Cardiotoxic Effects of Veratrum Lobelianum Alkaloids: Pilot Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Amir","family":"Taldaev","sequence":"first","affiliation":[{"name":"Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia"},{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9206-8632","authenticated-orcid":false,"given":"Roman P.","family":"Terekhov","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta V.","family":"Melnik","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria V.","family":"Belova","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"},{"name":"N.V. Sklifosovsky Research Institute for Emergency Medicine, 129090 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Kozin","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5915-7999","authenticated-orcid":false,"given":"Andrey A.","family":"Nedorubov","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana Ya.","family":"Pomerantseva","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina V.","family":"Ramenskaya","sequence":"additional","affiliation":[{"name":"A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/s41586-020-2650-9","article-title":"Biosynthesis of medicinal tropane alkaloids in yeast","volume":"585","author":"Srinivasan","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kurek, J. (2019). 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