Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial

Anti-microbial Effects In Vitro and In Vivo of Alstonia scholaris

“…In addition, preclinical safety evaluation results indicated that TA had a wide safety range in rats [ 20 ] or dogs [ 21 ] and no genotoxic effects [ 22 ]. Notably, the human pharmacokinetic results [ 23 ] were consistent with those of preclinical studies [ 14 , 24 ], and the four principal alkaloids (picrinine, scholaricine, vallesamine, and 19-epischolaricine, Fig. 1 ) were all distributed in blood, thus ensuring credibility and validity for further study.…”

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

“…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. No mortality or morbidity was observed during the course of the study.…”

“…Dose levels 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 influence on survivability, macroscopic and microscopic parameters [ 33 ] and the pharmacodynamics dose in rats was 15 mg/kg.bw [ 25 ]. In addition, a 2 mg/kg.bw dose was suggested for potential TA applications in humans [ 32 ]. In total, 12 female and 12 male purebred dogs were allocated into 4 groups, each containing 6 dogs (3 female and 3 male), for administration of TA capsules at doses of 0 (control), 20, 60, 120 mg/kg.bw.…”

“…In parallel with the above findings, in eligible healthy Chinese volunteers administered oral TA capsules at different doses (20, 40, 80 or 120 mg), AUC exposure was in the order: vallesamine > scholaricine > 19-epischolaricine > picrinine. Different patterns were observed whereby 19-epischolaricine, vallesamine and picrinine exhibited linear pharmacokinetic characteristics while scholaricine conformed to non-linear pharmacokinetics [ 32 ]. Based on the chemical profiles and metabolites of alkaloid extracts of leaves of A. scholaris , scholaricine, 19-epischolaricine, vallesamine and picrinine have been determined as the major indole alkaloids (Fig.…”

Pharmaceutical Application of Bio-actives from Alstonia Genus: Current Findings and Future Directions

“…In some of the cases, identified pharmacological activities were further provided a full proof basis for their traditional uses. In China, the monoterpenoid indole alkaloidal component from the A. scholaris leaves was formulated as a capsule and currently, it has completed the phase I clinical trial for the respiratory-related ailments (Li et al 2019). The obtained promising results provided additional value to the traditional uses of these plants for respiratory problems.…”