title: Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine and sophocarpine, in zebrafish (Danio rerio) embryos/larvae.
abstract: Matrine and sophocarpine are two major matrine-type alkaloids included in the traditional Chinese medicine (TCM) Kushen (the root of Sophora flavescens Ait.). They have been widely used clinically in China, however with few reports concerning their potential toxicities. This study investigated the developmental toxicity and neurotoxicity of matrine and sophocarpine on zebrafish embryos/larvae from 0 to 96/120h post fertilization (hpf). Both drugs displayed teratogenic and lethal effects with the EC50 and LC50 values at 145 and 240mg/L for matrine and 87.1 and 166mg/L for sophocarpine, respectively. Exposure of matrine and sophocarpine significantly altered spontaneous movement and inhibited swimming performance at concentrations below those causing lethality and malformations, indicating a neurotoxic potential of both drugs. The results are in agreement with most mammalian studies and clinical observations.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Zhao-Guang
authors.initials: ZG
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Li
authors.affiliation: Center for Molecular Metabolism, School of Environmental & Biological Engineering, Nanjing University of Science & Technology, 200 Xiao Ling Wei Street, Nanjing 210094, PR China. Electronic address: wang.junsong@gmail.com.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Qing-Wang
authors.initials: QW
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D054715:Cardiotoxins / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D009672:Notochord / Q000002:abnormalities; D011807:Quinolizines / Q000633:toxicity*; D013623:Tail / Q000002:abnormalities; D013723:Teratogens / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities; D000093842:Matrines
chemical_list: D000470:Alkaloids; D054715:Cardiotoxins; D009498:Neurotoxins; D011807:Quinolizines; D013723:Teratogens; C035933:sophocarpine; D000093842:Matrines
keywords: Developmental toxicity; Matrine; Neurotoxicity; Sophocarpine; Spontaneous movement; Swimming behavior; Zebrafish