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hERG Channel-Related Cardiotoxicity Assessment of 13 Herbal Medicines

한약재 13종의 hERG 채널 관련 심장독성 평가

  • Ha, Hyekyung (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Lee, Sion (New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Kim, Dong-Hyun (New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Seo, Chang-Seob (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Shin, Hyeun-kyoo (KM Science Research Division, Korea Institute of Oriental Medicine)
  • 하혜경 (한국한의학연구원 한의과학연구부) ;
  • 이시온 (대구경북첨단의료산업진흥재단 신약개발지원센터) ;
  • 김동현 (대구경북첨단의료산업진흥재단 신약개발지원센터) ;
  • 서창섭 (한국한의학연구원 한의과학연구부) ;
  • 신현규 (한국한의학연구원 한의과학연구부)
  • Received : 2021.05.03
  • Accepted : 2021.07.28
  • Published : 2021.09.01

Abstract

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC50 values were 3.158, 19.87, and 41.26 ㎍/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC50 value for each herbal medicine was more than 400 ㎍/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC50 values were more than 700 ㎍/mL. The IC50 value of quinidine against hERG was 1.021 𝜇M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

Keywords

Acknowledgement

본 연구는 한국한의학연구원의 '한방의료기관 한약처방의 안전성, 유효성 구축 사업 (KSN2013310)'에 대한 연구비 지원으로 수행되었으며, 이에 감사드립니다.

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