| ORIGINAL ARTICLES |
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Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats |
| Yun-Li Zhao1,3, Min Su2, Jian-Hua Shang2,3, Xia Wang2, Guy Sedar Singor Njateng4, Guang-Lei Bao2, Jia Ma2, Qing-Di Sun5, Fang Yuan2, Jing-Kun Wang2, Xiao-Dong Luo1,3 |
1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China;
2 Yunnan Institute of Medical Material, Kunming 650111, People's Republic of China;
3 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China;
4 Laboratory of Microbiology and Antimicrobial Substances, Faculty of Science, University of Dschang, P. O. Box 67, Dschang, Cameroon;
5 Jiangsu Nhwa Pharmaceutical Co., Ltd, Xuzhou 221009, People's Republic of China |
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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.
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| Keywords
Alstonia scholaris
Indole alkaloids
Acute toxicity
Chronic toxicity
Non-observed-adverse-effect-level
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| Fund:The authors are grateful to the Yunnan Major Science and Technology Project (2019ZF003) and National Key Research and Development Program of China (2017YFC1704007) for partial financial support. |
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Corresponding Authors:
Jing-Kun Wang, Xiao-Dong Luo
E-mail: wjkyimm@163.com;xdluo@mail.kib.ac.cn
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Issue Date: 06 May 2020
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