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

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 adminis-tered 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 bio-chemical 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.

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

Melodinus henryi is a good source of terpenoid indole alkaloids,and traditionally used as a folk medicine in the treatment of meningitis and fracture.In order to further exploit their potential uses,its anti-inflammatory and immunosuppressive activi-ties,safety evaluations and chemical profiles have been illustrated.Compared to the crude methanol extract from M.henryi and its non-alkaloidal fraction,the total alkaloidal fraction(MHTA)had the strongest anti-inflammatory and immunosup-pressive activities.In the acute oral toxicity assay,the half lethal dose(LD50)of MHTA was more than 2000 mg/kg.The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe,and might damage spleen,liver,kidney,and heart when the dose is higher than 1000 mg/kg.In addition,a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids.Thus,in regard with the potent side effects of MHTA,it should be used with caution in the development of phytomedicine.

Antidiabetic potential of methanol extracts from leaves of Piper umbellatum L. and Persea americana Mill.

Objective: To determine inhibitory activity of methanolic leaf extract of Piper umbellatum and Persea americana(P. americana)(traditionally used in Cameroon against diabetes) on β-glucosidase, β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities, enzymes involved in starch digestion or diabetic complications. Methods: The methanol extracts from Piper umbellatum and P. americana were prepared by maceration. To assess relative efficacy of these extracts, the determination of concentrations that were needed to inhibit 50% of enzyme activity was done, whereas, gas chromatography-mass spectrum was used to identify components from extracts that may be responsible for the activities. Results:The tested extracts strongly inhibited β-glucosidase, maltase-glucoamylase, aldose reductase and aldehyde reductase activities with IC50 ranging from(1.07 ± 0.03) to(31.77 ± 1.17) μg/mL.Among the tested extracts, P. americana was the most active against sensitive enzymes(IC50 of1.07 ± 0.03 to 15.63 ± 1.23). But, none of the extracts showed interesting inhibitory effect against β-glucosidase as their percentage inhibitions were less than 16%. From gas chromatographymass spectrum analysis, 10 and 8 compounds were identified in Piper umbellatum and P.americana extracts respectively, using NIST library 2014. Conclusions: Results of this study provide the scientific credential for a prospective usage of these plants to treat diabetes.