Preprint Article Version 1 This version not peer reviewed

Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo

These authors contributed equally and are considered as co-first authors
Version 1 : Received: 1 June 2017 / Approved: 2 June 2017 / Online: 2 June 2017 (08:07:04 CEST)

A peer-reviewed article of this Preprint also exists.

Yang, W.; Ma, L.; Li, S.; Cui, K.; Lei, L.; Ye, Z. Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo. Molecules 2017, 22, 943. Yang, W.; Ma, L.; Li, S.; Cui, K.; Lei, L.; Ye, Z. Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo. Molecules 2017, 22, 943.

Journal reference: Molecules 2017, 22, 943
DOI: 10.3390/molecules22060943

Abstract

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia 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.

Subject Areas

evodiamine; primary cultured neonatal rat cardiomyocytes; zebrafish; cardiotoxicity; oxidative stress

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