hERG Channel-Related Cardiotoxicity Assessment of 13 Herbal Medicines

Article information

J Korean Med. 2021;42(3):44-55

Publication date (electronic) : 2021 September 01

doi : https://doi.org/10.13048/jkm.21024

Hyekyung Ha ¹

, Sion Lee ²

, Dong-Hyun Kim ²

, Chang-Seob Seo ¹

, Hyeun-kyoo Shin ¹^,

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., Herbal Medicine 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 2021 May 3; Revised 2021 July 8; Accepted 2021 July 28.

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 μg/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 μg/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 μg/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: Herbal medicine; Cardiotoxicity; Cardiac arrhythmia; hERG potassium channel

% hERG activity=peak hERG tail current post-sample treatmentpeak hERG tail current pre-sample treatment×100

Fig. 1

hERG potassium channel activity and concentration-response curves of hERG activity by quinidine (hERG inhibitor) and 13 herbal medicines in hERG-HEK 293 cells. (A) Sample voltage-dependent current traces by hERG channel activities pre/post-treatment of quinidine (10 ìM). (B) Concentration dependent inhibition of hERG channel activities by quinidine. (C-O) Concentration dependent inhibition rate of hERG channel activities by 13 herbal medicine extracts. Data are presented as normalized %hERG activities and means ± standard error (n ≥ 4).

Table 1

The extraction yield of herbal medicines

Table 2

The IC₅₀ values of quinidine and herbal extracts on hERG potassium channel activity in HEK 293 cells.

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