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 (LD 50) 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.

The in vivo toxicity evaluation of leaf and root methanolic extracts of Tephrosia vogelii Hook.f using animal model

“…Medicinal plants are good candidates for the health care system as herbal medicines against diseases perpetrating human beings and animals' husbandry. Concurrently, their worth sources are attested beyond doubts in recent years whereby many researchers have paid more attention to the exploitation of the herbal medicines for the development of antimicrobial products [37][38][39]. However, little is done to carry out toxicity evaluation of such herbal medicines.…”

“…Twenty-seven rats were grouped into nine groups; each group consisted of three rats based to minor modification from previous studies [27,37]. Animal groups were housed in separate plastic cages for ease observation and treatments.…”

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

“…Thirteen-week sub-chronic toxicity studies are extensively used for evaluating long-term toxicological effects and safety profiles of drugs [ 37 ]. The current doses were selected based on the results of a chronic toxicity study on rats in which oral administration of TA (50, 100, or 300 mg/kg.bw) had no significant toxicity symptoms [ 33 ] and the pharmacodynamics dose in rats was 15 mg/kg.bw [ 25 ]. Another important reason for our dose selection was because a 2 mg/kg.bw dose was suggested for potential TA applications in humans [ 32 ], which guided us to limit the highest dose to 120 mg/kg.bw.…”

“…Despite the known chemical composition, substantial pharmacological effects and metabolic characteristics of TA, related toxicological studies such as acute toxicity test in mice and chronic in rats [ 33 ] as well as genotoxicity [ 34 ] have been studied by our group. Therefore, as part of a comprehensive preclinical program, toxicological assessment of TA and estimation of the appropriate doses in nonrodents are essential.…”

Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents

“…After administration, the general behavioral changes (i.e. altered locomotion, breathing difficulty, tremors, lethargy and convulsion) and mortality were observed at 0.5 h, 2 h, 4 h, 6 h, 10 h, and 24 h for the first day, and then recorded daily for 14 days [51]. Body weight, food and water intakes were assessedat the 4th, 7th, 11th and 14th day, and then weekly changes were calculated.…”