Cardiac toxicity of Triptergium wilfordii Hook F. may correlate with its inhibition to hERG channel

作者：Wei Zhao, Liping Xiao, Lanying Pan, Xianfu Ke, Yanting Zhang, Dian Zhong, Jianwei Xu, Fumin Cao, Liren Wu, Yuan Chen · 发表于：Heliyon · 年份：2019 · DOI：10.1016/j.heliyon.2019.e02527 · 被引用次数：25 · 研究领域：Phytochemistry and Bioactive Compounds、Natural Compounds in Disease Treatment、Beetle Biology and Toxicology Studies

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 (I hERG ) respectively. We further found that Celastrol, one of main components of TWHF, inhibits hERG with an IC 50 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.