Abstract：
BACKGROUND: Valeriana officinalis L., commonly known as \"valerian\", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear.
OBJECTIVE: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR).
METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR.
RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight.
CONCLUSIONS: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.
OBJECTIVE: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR).
METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR.
RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight.
CONCLUSIONS: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.
摘要：
背景：缬草，俗称“缬草”，是一种分布在美国北温带地区的传统草药，欧洲和亚洲。在中医中,缬草和它的根被用于治疗心脏和心灵的不安，心悸和失眠引起的内部抑郁的情绪和情绪。然而,缬草的安全性评价尚不清楚。
目的：本研究旨在评估遗传毒性，14天急性口服毒性试验，缬草根水提物(AEVR)90天亚慢性经口毒性试验和致畸试验。
方法：用细菌回复突变评估AEVR的遗传毒性，小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在14天的急性毒性研究中，昆明小鼠以96g/kg体重的剂量通过管饲法给药。在90天的亚慢性毒性研究中，Sprague-Dawley大鼠接受0、3.5、7和14g/kg体重的AEVR口服剂量。在致畸研究中，怀孕的Sprague-Dawley大鼠接受剂量为0、3.5、7和14g/kg体重的AEVR。
结果：AEVR没有显示任何基于细菌反向突变的遗传毒性，小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在急性毒性研究中,96g/kg体重剂量的AEVR不会导致雄性或雌性小鼠的死亡或异常行为。在亚慢性毒性研究中，在0、3.5、7、14克/千克体重的剂量下，对临床观察没有剂量相关影响，体重,器官重量,血液学,在雄性或雌性大鼠中检测AEVR的血清生化和尿液分析。致畸试验显示胚胎形成无明显毒理学变化,怀孕大鼠的体重，外部,在剂量为0、3.5、7、14g/kg体重的孕鼠和胎鼠中观察到的骨骼和内脏检查。
结论:体内或体外试验证明AEVR不表现出遗传毒性。根据急性口服毒性研究，在两种性别的小鼠中，AEVR的LD50均大于96g/kg体重。亚慢性毒性和致畸试验表明，AEVR的无观察不良反应水平（NOAEL）不低于14g/kg体重。本研究建立了AEVR的无毒剂量，为在一些国家和地区使用缬草作为新资源食品提供了基础。
目的：本研究旨在评估遗传毒性，14天急性口服毒性试验，缬草根水提物(AEVR)90天亚慢性经口毒性试验和致畸试验。
方法：用细菌回复突变评估AEVR的遗传毒性，小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在14天的急性毒性研究中，昆明小鼠以96g/kg体重的剂量通过管饲法给药。在90天的亚慢性毒性研究中，Sprague-Dawley大鼠接受0、3.5、7和14g/kg体重的AEVR口服剂量。在致畸研究中，怀孕的Sprague-Dawley大鼠接受剂量为0、3.5、7和14g/kg体重的AEVR。
结果：AEVR没有显示任何基于细菌反向突变的遗传毒性，小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在急性毒性研究中,96g/kg体重剂量的AEVR不会导致雄性或雌性小鼠的死亡或异常行为。在亚慢性毒性研究中，在0、3.5、7、14克/千克体重的剂量下，对临床观察没有剂量相关影响，体重,器官重量,血液学,在雄性或雌性大鼠中检测AEVR的血清生化和尿液分析。致畸试验显示胚胎形成无明显毒理学变化,怀孕大鼠的体重，外部,在剂量为0、3.5、7、14g/kg体重的孕鼠和胎鼠中观察到的骨骼和内脏检查。
结论:体内或体外试验证明AEVR不表现出遗传毒性。根据急性口服毒性研究，在两种性别的小鼠中，AEVR的LD50均大于96g/kg体重。亚慢性毒性和致畸试验表明，AEVR的无观察不良反应水平（NOAEL）不低于14g/kg体重。本研究建立了AEVR的无毒剂量，为在一些国家和地区使用缬草作为新资源食品提供了基础。
