title: Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5.
abstract: Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels Na(V)1.3-1.5 and exhibited the strongest ability to inhibit Na(V)1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the Na(V)1.5 channel. The effects of VAs on Na(V)1.3 and Na(V)1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively.
authors.affiliation: College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. wang.gan@outlook.com.|Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences &amp; Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. wang.gan@outlook.com.
authors.forename: Gan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. rongmingqiang@mail.kiz.ac.cn.
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Rong
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. qiongqiongbird@163.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. liuyaping@mail.kib.ac.cn.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. longchb@163.com.
authors.forename: Cheng-Bo
authors.initials: CB
authors.lastname: Long
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. pingmeng@yeah.net.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
authors.affiliation: College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. 2013116051@njau.edu.cn.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Yao
authors.affiliation: College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. rlai@mail.kiz.ac.cn.|Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences &amp; Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. rlai@mail.kiz.ac.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. xdluo@mail.kib.ac.cn.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Luo
mesh_terms: D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D008251:Macaca; D008297:Male; D051379:Mice; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000502:physiology; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000502:physiology; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000502:physiology*; D018517:Plant Roots; D051381:Rats; D014703:Veratrum
chemical_list: D000470:Alkaloids; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: NaV1.5; Veratrum taliense; cardiovascular toxicity