Abstract
Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24 h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.
Highlights
Computational toxicology aims to complement other measures of toxicity by helping to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drug development [1]
The present study focuses on this prediction of a cardiotoxic effect of a major bioactive alkaloid as an herb with mild toxicity in “Shen Nong’s Herbal Classic”, China’s most ancient herbal medicine present in Evodia rutaecarpa (E. rutaecarpa), evodiamine
The present study investigated cardiotoxicity of evodiamine on primary neonatal rat Previous investigations havethe indicated that evodiamine has a beneficial effect incultured cardiovascular diseases [7,8,9]
Summary
Computational toxicology aims to complement other measures of toxicity by helping to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drug development [1]. A range of in silico methods have been developed to predict the toxicity of chemicals. Quantitative structure-activity relationship (QSAR) models are widely used for the early prediction of potential toxic effects. This approach assumes that chemicals with similar structural features operate via similar mechanisms [2]. Traditional Chinese herbs are widely used to produce important preparations employed in Oriental medicine. The therapeutic efficacy of this type of medicine is supported by clinical observations, it still lacks a formal evidence base relating to the pharmacodynamic effects and potential toxicity. Further studies are urgently required to determine the toxicity of traditional Chinese herbal preparations. As traditional Chinese medicines contain multiple chemical components, toxicity prediction is challenging.
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