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Although the efficacy and the health care advantages of Chinese herbal medicine (CHM) have become increasingly recognized worldwide, the potential side effects and toxicity still restrict its broader application. This study established and applied an integrated platform anchored on automatic patch clamp system to screen and evaluate a collection of CHM extracts, compositions and monomeric compounds for in vitro cardiac toxicity. Of 1036 CHM samples screened, 2.79% significantly inhibited hERG channel activity. Among them, Strychnine was identified for the first time as a potent hERG inhibitor with an IC 5 0 of 6. 6 5 ± 1. 0 4 μ M in comparison to that of Dofetilide at 1. 8 0 ± 0. 2 4 μ M and Quinidine at 7. 4 2 ± 0. 5 4 μ M. Langendorff-perfusion experiments confirmed that strychnine increased QT interphase from 7 1. 6 9 ± 5. 3 4 ms to 9 8. 6 1 ± 5. 5 4 ms and decreased heart rates from 2 2 7. 6 5 ± 5. 4 0 bmp to 1 6 2. 9 1 ± 1 4. 7 0 bmp in isolated rat hearts. The cardiac toxicity effect of strychnine appears to be specific to hERG channel since an in vitro multiplex imaging analysis showed that it did not affect cellular phenotypes such as cell vitality, nucleus area, mitochondria mass and function, nor intracellular calcium in rat primary myocytes. This integrated high-throughput hERG patch clamp and high-content multi-parameter imaging cardiac toxicity screen approach should be useful for large-scale preclinical evaluation of complex Chinese herbal medicine. [ABSTRACT FROM AUTHOR]