Cardiac toxicity of Triptergium wilfordii Hook F. may correlate with its inhibition to hERG channel
Wei Zhao,
Liping Xiao,
Lanying Pan,
Xianfu Ke,
Yanting Zhang,
Dian Zhong,
Jianwei Xu,
Fumin Cao,
Liren Wu,
Yuan Chen
Affiliations
Wei Zhao
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Liping Xiao
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Lanying Pan
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Xianfu Ke
Zhejiang Key Laboratory for Laboratory Animal and Safety Research, Zhejiang Academy of Medical Sciences, PR China
Yanting Zhang
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Dian Zhong
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Jianwei Xu
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Fumin Cao
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China
Liren Wu
Zhejiang Key Laboratory for Laboratory Animal and Safety Research, Zhejiang Academy of Medical Sciences, PR China; Corresponding author.
Yuan Chen
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Lin'an 311300, PR China; The State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 666 Wusu St, Lin'an 311300, PR China; Corresponding author.
Tripterygium wilfordii Hook F. (TWHF) is a Chinese traditional medicine with cardiac toxicities. However, the mechanism of acute cardiac toxicity is not very clear. By using patch clamp techniques, we found that 0.05 mg/ml and 0.1 mg/ml of the aqueous crude extract of TWHF inhibit 21.4 ± 1.6% and 86.7 ± 5.7% (n = 5) of hERG current Amplitudes (IhERG) respectively. We further found that Celastrol, one of main components of TWHF, inhibits hERG with an IC50 of 0.83 μM. Additional mutagenesis studies show that mutations of T623A, S624A and F656A significantly alter the inhibition and S624A has the strongest effect, supported by our docking model. Our data suggest that inhibition of hERG channel activity by Celastrol contributed to TWHF cardiotoxicity.
