Aconitum carmichaelii triggers neurotoxicity and Parkinson-like symptoms through initiation of ROS-mitochondrial apoptosis and the Nox5/DJ-1 signaling pathway  

作　　者：Meijun Pang Xin Song Yaodong Miao Yiwen Wang Chang Zhou Zihan Geng Jiayin Du Bernard Moussian Yanfang Su Xiuyun Liu Dong Ming 

机构地区：[1]Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin,China [2]Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,China [3]School of Pharmaceutical Science and Technology,Tianjin University,Tianjin,China [4]Academy of Medical College,Tianjin University,Tianjin,China [5]Animal Genetics,Interfaculty Institute of Cell Biology,University of Tübingen,Tübingen,Germany [6]UniversitéCôte d’Azur,Nice,France [7]Department of Biomedical Engineering,College of Precision Instruments and Optoelectronics Engineering,Tianjin University,Tianjin,China

出　　处：《BMEMat(BioMedical Engineering Materials)》2023年第2期153-167,共15页生物医学工程材料（英文）

基　　金：National Key Research and Development Program,Grant/Award Number:2021YFF1200600;China Postdoctoral Science Foundation,Grant/Award。

摘　　要：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 bydownregulating DJ-1 and activating Nox5,and further triggered cell apoptosis through the bax/bcl2a-caspase-9 pathway in zebrafish larva.Mitochondrial protection-relatedgenes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress.The ROS scavenger-NAC significantly alleviated neurotoxicity in the 20mg/mL group.Conclusion:The study reveals the potential mechanism of A.carmichaelii-induced neurotoxicity and provides new insights in to a significant risk marker of A.carmichaelii poisoning.

关 键 词：Aconitum Carmichaelii apoptosis NEUROTOXICITY OXIDATIVESTRESS ZEBRAFISH 

分 类 号：R742.5[医药卫生—神经病学与精神病学]