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 TA-treated 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.

Graphic Abstract

中文翻译：

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阿尔斯托尼亚 (L.) R. Br. 叶中吲哚生物碱提取物的急性和亚慢性毒性。在比格犬中。

Alstonia schoolris (L.) R. Br.是一种常绿热带植物，富含具有显着生理活性的吲哚生物碱，在我国传统上用于治疗呼吸道疾病。本研究旨在确定学者叶生物碱提取物 (TA) 对非啮齿动物的毒性特征。口服单剂量（4 g/kg.bw）后，观察到许多短暂症状，如步态不稳、流口水、呕吐和口周粘膜发红，但没有出现与治疗相关的死亡。对一系列 TA 剂量（20、60 和 120 mg/kg.bw）进行了为期 13 周的治疗期的亚慢性毒性研究，随后进行了 4 周的恢复观察。除了120 mg/kg.bw治疗组中大多数动物出现呕吐和流口水外，TA治疗的动物没有观察到临床变化。TA治疗组动物和对照动物之间的心电图、骨髓、尿液、粪便、血液学和临床化学分析数据具有​​可比性。TA治疗组和对照组之间的相对器官重量和组织病理学特征没有明显差异。因此，TA 的未观察到不良反应水平 (NOAEL) 确定为 120 mg/kg.bw。我们的研究结果进一步丰富了学者吲哚生物碱提取物的安全性数据库，该提取物具有作为新候选药物的潜在用途。

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