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Cardiotoxicity assessment of 31 herbal formulae by activity of hERG potassium channel in HEK 293 cells

hERG 칼륨채널 활성도 변화에 따른 31종 한약처방의 심장독성 평가

  • Ha, Hyekyung (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Jin, Seong Eun (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) ;
  • 진성은 (한국한의학연구원 한의과학연구부) ;
  • 이시온 (대구경북첨단의료산업진흥재단 신약개발지원센터) ;
  • 김동현 (대구경북첨단의료산업진흥재단 신약개발지원센터) ;
  • 서창섭 (한국한의학연구원 한의과학연구부) ;
  • 신현규 (한국한의학연구원 한의과학연구부)
  • Received : 2021.11.15
  • Accepted : 2022.02.22
  • Published : 2022.03.01

Abstract

Objectives: Drug-induced blockade of the human ether-à-go-go related gene (hERG) potassium ion channel causes acquired long QT syndrome, which is known to cause cardiac arrhythmias and be fatal. To establish safety evidence of herbal formulae, we evaluated the effects of 31 herbal formulae on hERG channel activity. Methods: The current through hERG channel was measured by changing the membrane voltage before and after treatment with 31 herbal formulae in HEK 293 cell overexpressing hERG channel using a whole-cell patch clamp system. The current-voltage curves and the activity curves were fitted, and the hERG activity and 50% inhibitory concentration (IC50) according to each herbal formula were calculated. Results: Chokyungjongok-tang, Oncheong-eum, and Cheongsangbangpung-tang strongly inhibited the hERG activity, with IC50 values of 67.67, 141.2, and 296.3 ㎍/mL, respectively. Yeonkyopaedok-san, Eunkyo-san, Ukgan-san gajinphibanha, Daegunjoong-tang (except Oryzae gluten), Insamyangyoung-tang, Banhahubak-tang, SokyungHwalhyul-tang, Jodeung-san, Hyeonggaeyeongyo-tang, and Bangkeehwangkee-tang weakly inhibited hERG activity, with IC50 values ranging from 400 to 1000 ㎍/mL. The other 18 herbal formulae showed very weak hERG activity inhibition of less than 50% at the highest concentration (1000 ㎍/mL). Conclusion: This study provided safety information on cardiotoxicity by cardiac arrhythmia risk assessment of herbal formulae, and is expected to be a reference data for predicting the safety and risk of herbal formulae.

Keywords

Acknowledgement

본 연구는 한국한의학연구원에서 지원하는 '한방의료기관 한약처방 안전성·유효성 구축 사업(KSN2013310)'에 의해 수행되었습니다.

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