Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway
Meijun Pang,
Xin Song,
Yaodong Miao,
Yiwen Wang,
Chang Zhou,
Zihan Geng,
Jiayin Du,
Bernard Moussian,
Yanfang Su,
Xiuyun Liu,
Dong Ming
Affiliations
Meijun Pang
Academy of Medical Engineering and Translational Medicine Tianjin University Tianjin China
Xin Song
Academy of Medical Engineering and Translational Medicine Tianjin University Tianjin China
Yaodong Miao
Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Tianjin China
Yiwen Wang
School of Pharmaceutical Science and Technology Tianjin University Tianjin China
Chang Zhou
Academy of Medical College Tianjin University Tianjin China
Zihan Geng
Academy of Medical College Tianjin University Tianjin China
Jiayin Du
Academy of Medical College Tianjin University Tianjin China
Bernard Moussian
Animal Genetics Interfaculty Institute of Cell Biology University of Tübingen Tübingen Germany
Yanfang Su
School of Pharmaceutical Science and Technology Tianjin University Tianjin China
Xiuyun Liu
Academy of Medical Engineering and Translational Medicine Tianjin University Tianjin China
Dong Ming
Academy of Medical Engineering and Translational Medicine Tianjin University Tianjin China
Abstract Background Aconitum carmichaelii, the mother root of Aconitum, has a long‐applied history for treating many diseases in China. Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity. The molecular mechanisms underlying A. carmichaelii‐induced neurotoxicity are poorly understood. Methods We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A. carmichaelii. In addition to the behavior and neuronal activity testing, gene expression of neuronal oxidative stress, and apoptosis levels were also analyzed. Results In contrast to the excitatory effect of low‐dose A. carmichaelii decoction, hypoactivity of locomotor behavior, and neural activity, especially telencephalon, were detected in the 20 mg/mL group. High doses of A. carmichaelii induced excessive ROS by downregulating DJ‐1 and activating Nox5, and further triggered cell apoptosis through the bax/bcl2a‐caspase‐9 pathway in zebrafish larva. Mitochondrial protection‐related genes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress. The ROS scavenger‐NAC significantly alleviated neurotoxicity in the 20 mg/mL group. Conclusion The study reveals the potential mechanism of A. carmichaelii‐induced neurotoxicity and provides new insights into a significant risk marker of A. carmichaelii poisoning.