Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5.

Gan Wang,Qiong Li,Hui-Ming Yao,Ren Lai,Ming-Qiang Rong,Ya-Ping Liu,Xiao-Dong Luo,Cheng-Bo Long,Ping Meng

doi:10.3390/toxins8010012

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 NaV1.3–1.5 and exhibited the strongest ability to inhibit NaV1.5, 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 NaV1.5 channel. The effects of VAs on NaV1.3 and NaV1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively.

Highlights

IntroductionSeveral species of the Veratrum genus, such as V. album, V. californicum, V. viride and V. nigrum, are poisonous to humans and animals, and the principal toxic components are steroid alkaloids
Several species of the Veratrum genus, such as V. album, V. californicum, V. viride and V. nigrum, are poisonous to humans and animals, and the principal toxic components are steroid alkaloids.More than 200 different alkaloids belonging to seven groups have been identified from the Veratrum species [1,2]
This study investigated the cardiovascular two Veratrum alkaloids (VAs) study the cardiovascular toxicities oftoxicities two VAsof(isorubijervine and rubijervine) and their and their interactions with sodium channel subtypes

Summary

Introduction

Several species of the Veratrum genus, such as V. album, V. californicum, V. viride and V. nigrum, are poisonous to humans and animals, and the principal toxic components are steroid alkaloids. More than 200 different alkaloids belonging to seven groups have been identified from the Veratrum species [1,2]. Humans and animals exhibit toxic symptoms after the ingestion of Veratrum alkaloids, including vomiting and abdominal pain, followed by cardiovascular disorders, such as bradycardia, hypotension, cardiac arrhythmias and death. Many studies have investigated the possible mechanisms of Veratrum alkaloid (VA) toxicities, but only a few works focus on the ion channel. The effects of the VA veratridine on Na current behavior were first detected on neuroblastoma cells using single-channel and whole-cell voltage-clamp recordings [3].

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Discussion

Conclusion