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Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats.
Natural Products and Bioprospecting ( IF 4.8 ) Pub Date : 2020-03-31 , DOI: 10.1007/s13659-020-00237-1
Yun-Li Zhao 1, 2 , Min Su 3 , Jian-Hua Shang 2, 3 , Xia Wang 3 , Guy Sedar Singor Njateng 4 , Guang-Lei Bao 3 , Jia Ma 3 , Qing-Di Sun 5 , Fang Yuan 3 , Jing-Kun Wang 3 , Xiao-Dong Luo 1, 2
Affiliation  

Abstract

Alstonia scholaris (L.) R. Br. (Apocynaceae) is an evergreen tree that has been used to treat lung diseases. In this study, the toxicity profile of indole alkaloids from leaves of A. scholaris was investigated. In acute toxicity tests, mice were administered total alkaloids (TA) and five indole alkaloids. In a chronic toxicity test, rats were continuously administered TA (50, 100, and 300 mg/kg bw) for 13 weeks, followed by a 4-week recovery. A single administration of TA affected the behavior of mice, and at 12.8 g/kg bw, prone position, shortness of breath, wheezing, and convulsion were observed. The half-lethal dose (LD50) in mice was 5.48 g/kg bw, almost 2740 times the clinical dose in humans. Among the five indole alkaloids, the maximum tolerance dose in mice ranged from 0.75 to 4 g/kg bw. The TA-treated rats did not die and showed no adverse effects or dose-dependent changes in weight or food and water consumption, despite fluctuations in hematological and biochemical parameters compared with historical data. Furthermore, both gross and histopathological observations revealed no abnormalities in any organ. With daily oral administration to rats, the non-observed-adverse-effect-level of TA was 100 mg/kg bw. The results indicate that TA is safe for clinical use.

Graphic Abstract



中文翻译:


Alstonia sexyis (L.) R. Br. 叶中吲哚生物碱的急性和慢性毒性。在小鼠和大鼠中。


 抽象的


阿尔斯托尼亚学术(L.) R. Br. (夹竹桃科)是一种常绿乔木,已用于治疗肺部疾病。在本研究中,研究了学术植物叶子中吲哚生物碱的毒性特征。在急性毒性试验中,给小鼠注射了总生物碱(TA)和五种吲哚生物碱。在慢性毒性试验中,大鼠连续服用 TA(50、100 和 300 mg/kg bw)13 周,随后 4 周恢复。单次给予 TA 会影响小鼠的行为,在 12.8 g/kg 体重时,观察到俯卧位、呼吸短促、喘息和抽搐。小鼠的半致死剂量(LD 50 )为5.48克/千克体重,几乎是人类临床剂量的2740倍。 5种吲哚生物碱中,小鼠最大耐受剂量为0.75~4 g/kg体重。尽管与历史数据相比,血液学和生化参数发生了波动,但接受 TA 治疗的大鼠并未死亡,并且体重或食物和水消耗量没有出现任何副作用或剂量依赖性变化。此外,肉眼观察和组织病理学观察均未发现任何器官异常。大鼠每日口服给药时,未观察到 TA 不良反应水平为 100 mg/kg bw。结果表明 TA 临床使用是安全的。

 图文摘要

更新日期:2020-03-31
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