Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats

Natural Products and Bioprospecting

Qing-Di Sun¹  Guy Sedar Singor Njateng²  Yun-Li Zhao³  Xiao-Dong Luo³  Min Su⁴  Fang Yuan⁴  Jing-Kun Wang⁴  Xia Wang⁴  Guang-Lei Bao⁴  Jia Ma⁴  Jian-Hua Shang⁴ 

[1] Jiangsu Nhwa Pharmaceutical Co., Ltd;Laboratory of Microbiology and Antimicrobial Substances, Faculty of Science, University of Dschang;State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences;Yunnan Institute of Medical Material;

关键词: Alstonia scholaris;    Indole alkaloids;    Acute toxicity;    Chronic toxicity;    Non-observed-adverse-effect-level;   

DOI  :  10.1007/s13659-020-00237-1

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown