1KM Science Research Division, Korea Institute of Oriental Medicine
2New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation
Correspondence to: Hyeun-Kyoo Shin, KMD, Ph.D., KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daejeon 34054, Republic of Korea, Tel: +82-42-868-9464, Fax: +82-42-864-2120, E-mail: hkshin@kiom.re.kr
Received November 15, 2021 Revised February 9, 2022 Accepted February 22, 2022
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 μg/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 μg/mL. The other 18 herbal formulae showed very weak hERG activity inhibition of less than 50% at the highest concentration (1000 μg/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.
Effects of 31 herbal formulae on hERG potassium channel activity in the voltage–clamp assay using HEK 293 cells. Concentration–activity curves fitted with the three parameters logistic equation for block of hERG activity by quinidine (positive control) and herbal formulae, respectively. Data are presented means ± standard error (n ≥ 4 per each point).
Table 1
The extraction yield and the half–maximal inhibitory concentration (IC50) values of herbal formulas on hERG potassium channel activity
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