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

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.

Keywords: Acute toxicity; Alstonia scholaris; Chronic toxicity; Indole alkaloids; Non-observed-adverse-effect-level.

Fig. 1

HPLC/UV chromatograms of total alkaloids (285 nm). A. Four major alkaloids from leaf and echitamine from bark of A. scholaris. B. HPLC/UV chromatograms of total alkaloids