Safety Evaluation of Main Alkaloids from Rhizoma Coptidis

Ethnopharmacological Relevance: Rhizoma Coptidis (RC), a widely used traditional Chinese medicine, has been used for the treatment of heat-clearing and detoxifying, but there is very little information on its safety.

Aim Of The Study: To provide information on the safety of RC, we evaluated the toxicity of the crude RC and RC alkaloids (berberine, coptisine, palmatine and epiberberine) including cytotoxicity, acute toxicity in mice and sub-chronic toxicity in rats.

Materials And Methods: The cytotoxicity of RC alkaloids was tested in HepG2 and 3T3-L1 cells by the MTT assay. The acute toxicity of RC alkaloids was tested in mice and the mortality was calculated at the end of experiment. For sub-chronic toxicity study, the rats were treated with the RC alkaloids at a dose of 156 mg/kg/day and RC at a dose of 521 mg/kg/day for 90 days. Mortality, clinical signs, body weight changes, organ weights, urinalysis and hematological parameters, gross necropsy and histopathology were monitored during the study period.

Results: The cell assay indicates that the IC(50) values of berberine, coptisine, palmatine and epiberberine in HepG2 cells were 48.17, 64.81, 112.80 and 120.58 μg/mL, which in 3T3-L1 cells were 41.76, 56.48, 84.32 and 104.18 μg/mL, respectively. In the acute toxicity assay, the LD(50) values of four alkaloids were 713.57, 852.12, 1533.68 and 1360 mg/kg, respectively. However, in the sub-chronic toxicity study, no mortality and morbidity were observed which could be related to RC alkaloids and RC treatment. Besides, there was no abnormality in clinical signs, body weights, organ weights, urinalysis, hematological parameters, gross necropsy and histopathology in any of the animals after the oral administration of RC alkaloids and RC.

Conclusions: Taking these results together, we came to the conclusion that the toxicity of berberine is the maximum and palmatine is the minimal in four RC alkaloids. The currently recommended doses of RC alkaloids and RC consumed are relatively safe.