Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of <i>Alstonia scholaris</i> (L.) R. Br. in Beagle Dogs

doi:10.1007/s13659-020-00246-0

Natural Products and Bioprospecting

2020, Vol. 10

Issue (4) : 209-220 DOI: 10.1007/s13659-020-00246-0

ORIGINAL ARTICLES

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Yun-Li Zhao^1,3, Min Su², Jian-Hua Shang^2,3, Xia Wang², Guang-Lei Bao², Jia Ma², Qing-Di Sun⁴, Fang Yuan², Jing-Kun Wang², Xiao-Dong Luo^1,3

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 Jiangsu Nhwa Pharmaceutical Co., Ltd, Xuzhou 221009, People's Republic of China

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Abstract Alstonia scholaris (L.) R. Br., an evergreen tropical plant rich in indole alkaloids with significant physiological activity, is traditionally used to treat respiratory diseases in China. This study was conducted to establish the toxicity profile of the alkaloid extract (TA) of A. scholaris leaves in non-rodents. After oral administration of a single dose (4 g/kg.bw), a number of transient symptoms, such as unsteady gait, drooling, emesis, and reddening of peri-oral mucosa, were observed, but no treatment-related mortality. A sub-chronic toxicity study with a range of doses of TA (20, 60 and 120 mg/kg.bw) was conducted for a 13-week treatment period, followed by 4-week recovery observation. Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group, no clinical changes were observed in TA-treated animals. Data from electrocardiography, bone marrow, urine, fecal, hematology and clinical chemistry analyses were comparable between TAtreated and control animals. No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups. Accordingly, the non-observed-adverse-effect-level (NOAEL) of TA was established as 120 mg/kg.bw. Our results add further knowledge to the safety database for indole alkaloid extracts from A. scholaris with potential utility as novel drug candidates.

Keywords Alstonia scholaris Indole alkaloids Acute toxicity Sub-chronic toxicity Beagle dog Non-observedadverse-effect-level

Fund:The authors are grateful to Yunnan Major Science and Technology Project (2019ZF003, 2019FY003004), and the National Key Research and Development Program of China (2017YFC1704007), and the general program of applied basic research of Yunnan province (2019FB116) for partial financial support.

Corresponding Authors: Jing-Kun Wang, Xiao-Dong Luo E-mail: wjkyimm@163.com;xdluo@mail.kib.ac.cn

Issue Date: 19 August 2020

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	Yun-Li Zhao
	Min Su
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	Xia Wang
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	Jia Ma
	Qing-Di Sun
	Fang Yuan
	Jing-Kun Wang
	Xiao-Dong Luo

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Yun-Li Zhao,Min Su,Jian-Hua Shang, et al. Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs[J]. Natural Products and Bioprospecting, 2020, 10(4): 209-220.

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http://npb.kib.ac.cn/EN/10.1007/s13659-020-00246-0 OR http://npb.kib.ac.cn/EN/Y2020/V10/I4/209

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