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JKM > Volume 40(2); 2019 > Article
Choi, Kwon, Lee, Seo, and Shin: Cardiac Safety Assessment of Medicinal Herbal Formulas Using hERG-HEK 293 cell

Abstract

Objectives

The correlation between medicinal herbal formulas and a risk of cardiotoxicity has been controversial. Thus, this study investigated cardiac safety assessment of 52 most commonly used medicinal herbal formulas.

Methods

We evaluated the in vitro effects of medicinal herbal formulas on recombinant human embryonic kidney 293 (HEK 293) cell line expressing human ether-a-go-go-related gene (hERG) potassium channel.

Results and Conclusion

Our results demonstrated that all of 52 medicinal herbal formulas did not show inhibition of hERG current in hERG-HEK 293 recombinant cells. In conclusion, these safety data suggest that 52 medicinal herbal formulas were not associated with an increased risk of cardiotoxicity in hERG-HEK 293 recombinant cells.

%hERGactivity=Current post compound treatmentCurrent pre compound treatment×100

Fig. 1
In vitro effects of medicinal herbal formulas used to treat endocrine and metabolic diseases on the hERG current in hERG-HEK 293 recombinant cells. Panel A and B show the dose-response curve of the positive control, Quinidine (panel A, 30 – 0.1 μM) and Bangpungtongseong-san (panel B, 400 – 1.6 μg/ml) in HEK 293 cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f1.gif
Fig. 2
In vitro effects of medicinal herbal formulas used to treat mental and behavioural disorders on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – E show the dose-response curve of Gamisoyo-san (panel A, 400 – 1.6 μg/ml), Guibi-tang (panel B, 400 – 1.6 μg/ml), Chengsimyeunjaeum (panel C, 400 – 1.6 μg/ml), Cheonwangbosim-dan (panel D, 400 – 1.6 μg/ml) and Buhnsimgieum (panel E, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f2.gif
Fig. 3
In vitro effects of medicinal herbal formulas used to treat musculoskeletal and joint diseases on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – F show the dose-response curve of Oyaksungi-san (panel A, 400 – 1.6 μg/ml), Dangguisu-san (panel B, 400 – 1.6 μg/ml), Jakyak gamcho-tang (panel C, 400 – 1.6 μg/ml), Daeyoung-jeon (panel D, 400 – 1.6 μg/ml), ), Galgeun-tang (panel E, 400 – 1.6 μg/ml) and Ojeok-san (panel F, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f3.gif
Fig. 4
In vitro effects of medicinal herbal formulas used to treat respiratory diseases on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – I show the dose-response curve of Hyangso-san (panel A, 400 – 1.6 μg/ml), Gyeji-tang (panel B, 200 – 0.8 μg/ml), Mahwang-tang (panel C, 400 – 1.6 μg/ml), Gumiganghwal-tang (panel D, 400 – 1.6 μg/ml), Sosiho-tang (panel E, 400 – 1.6 μg/ml), Saengmaek-san (panel F, 400 – 1.6 μg/ml), Samsoeum (panel G, 400 – 1.6 μg/ml), Socheongryong-tang (panel H, 400 – 1.6 μg/ml) and Insampaedok-san (panel I, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f4.gif
Fig. 5
In vitro effects of medicinal herbal formulas used to treat digestive diseases on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – O show the dose-response curve of Yeongyechulgam-tang (panel A, 400 – 1.6 μg/ml), Hyangsayukgunja-tang (panel B, 400 – 1.6 μg/ml), Gwakhyangjeonggi-san (panel C, 400 – 1.6 μg/ml), Maekmundong-tang (panel D, 400 – 1.6 μg/ml) and Samryeongbaechul-san (panel E, 400 – 1.6 μg/ml), Bojungikgi-tang (panel F, 400 – 1.6 μg/ml), Banhabakchulcheonma-tang (panel G, 400 – 1.6 μg/ml), Samchulgeonbi-tang (panel H, 400 – 1.6 μg/ml), Pyeongwi-san (panel I, 400 – 1.6 μg/ml), Banhasasim-tang (panel J, 400 – 1.6 μg/ml), Hyangsapyeongwi-san (panel K, 400 – 1.6 μg/ml), Naeso-san (panel L, 400 – 1.6 μg/ml), Yijung-tang (panel M, 400 – 1.6 μg/ml), Yijin-tang (panel N, 400 – 1.6 μg/ml) and Bulwhangeumjeionggi-san (panel O, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f5.gif
Fig. 6
In vitro effects of medicinal herbal formulas used to treat genitourinary diseases on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – L show the dose-response curve of Yukmijihwang-tang (panel A, 400 – 1.6 μg/ml), Oryeong-san (panel B, 400 – 1.6 μg/ml), Gyejibokryeong-hwan (panel C, 200 – 0.8 μg/ml), Palmijihwang-hwan (panel D, 400 – 1.6 μg/ml), Onkyung-tang (panel E, 400 – 1.6 μg/ml), Yongdansagan-tang (panel F, 400 – 1.6 μg/ml), Paljung-san (panel G, 200 – 0.8 μg/ml), Wiryeong-tang (panel H, 400 – 1.6 μg/ml) Gamisoyo-san (panel I, 400 – 1.6 μg/ml), Jaeumganghwa-tang (panel J, 400 – 1.6 μg/ml), Hwanglyeonhaedok-tang (panel K, 400 – 1.6 μg/ml) and Palmul-tang (panel L, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f6.gif
Fig. 7
In vitro effects of medicinal herbal formulas used to treat symptoms, signs and abnormal clinical and laboratory findings, NEC (not elsewhere classified) on the hERG potassium channel in hERG-HEK 293 recombinant cells. Panel A – D show the dose-response curve of Sagunja-tang (panel A, 400 – 1.6 μg/ml), Sibjeondaebo-tang (panel B, 400 – 1.6 μg/ml), Ssanghwa-tang (panel C, 400 – 1.6 μg/ml) and Samul-tang (panel D, 400 – 1.6 μg/ml) in hERG-HEK 293 recombinant cells. Data are the mean ± SEM (n=3).
jkm-40-2-94f7.gif
Table 1
Medicinal herbal formulas of target diseases
Classification of disease Medicinal herbal formulas Yield (%) Original
Endocrine and metabolic disorders Bangpungtongseong-san 17.7 Donguibogam

Mental and behavioural disorders Gamisoyo-san 26.8 Bangyakhappyeon
Guibi-tang 24.3 Donguibogam
Chengsimyeunjaeum 13.0 Donguibogam
Cheonwangbosim-dan 21.3 Donguibogam
Buhnsimgieum 14.5 Bangyakhappyeon

Respiratory diseases Hyangso-san 13.4 Donguibogam
Gyeji-tang 9.8 Donguibogam
Mahwang-tang 4.5 Donguibogam
Gumiganghwal-tang 22.8 Donguibogam
Sosiho-tang 22.9 Donguibogam
Saengmaek-san 26.5 Donguibogam
Samsoeum 18.6 Donguibogam
Socheongryong-tang 21.7 Donguibogam
Insampaedok-san 24.3 Donguibogam

Digestive diseases Yeongyechulgam-tang 12.7 Donguibogam
Hyangsayukgunja-tang 12.9 Donguibogam
Gwakhyangjeonggi-san 12.8 Donguibogam
Maekmundong-tang 9.2 Donguibogam
Samryeongbaechul-san 14.1 Donguibogam
Bojungikgi-tang 25.4 Donguibogam
Banhabakchulcheonma-tang 17.6 Donguibogam
Samchulgeonbi-tang 24.5 Donguibogam
Pyeongwi-san 23.4 Donguibogam
Banhasasim-tang 14.9 Donguibogam
Hyangsapyeongwi-san 18.7 Donguibogam
Naeso-san 11.9 Donguibogam
Yijung-tang 24.8 Donguibogam
Yijin-tang 18.5 Donguibogam
Bulwhangeumjeionggi-san 12.4 Bangyakhappyeon

Musculoskeletal and joint diseases Oyaksungi-san 24.4 Donguibogam
Dangguisu-san 16.9 Donguibogam
Jakyak gamcho-tang 19.3 Donguibogam
Daeyoung-jeon 27.5 Bangyakhappyeon
Galgeun-tang 12.6 Euihakipmun
Ojeok-san 21.0 Donguibogam

Genitourinary diseases Yukmijihwang-tang 27.0 Yihaksimo
Oryeong-san 22.7 Donguibogam
Gyejibokryeong-hwan 11.8 Donguibogam
Palmijihwang-hwan 24.7 Donguibogam
Onkyung-tang 30.6 Donguibogam
Yongdansagan-tang 18.5 Donguibogam
Paljung-san 9.3 Donguibogam
Wiryeong-tang 12.5 Donguibogam
Gamisoyo-san 19.4 Donguibogam
Jaeumganghwa-tang 20.8 Donguibogam
Hwanglyeonhaedok-tang 17.1 Donguibogam
Palmul-tang 25.9 Donguibogam

Symptoms, signs and abnormal clinical and laboratory findings, NEC (not elsewhere classified) Sagunja-tang 22.3 Donguibogam
Sibjeondaebo-tang 22.9 Donguibogam
Ssanghwa-tang 25.5 Donguibogam
Samul-tang 33.3 Donguibogam

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