Toxicology of a Peruvian botanical remedy to support healthy liver function.
BACKGROUND
The purpose of these studies was to determine the safety of a botanical treatment for supporting healthy liver function developed in Peru. The formulation, A4+, contains extracts of Curcuma longa L. rhizome (A4R), Cordia lutea Lam. flower (A4F) and Annona muricata L. leaf (A4L). The tests were used to support an application for a non-traditional Natural Health Product Licence from the Natural Health Product Directorate of Health Canada and future clinical trials.


METHODS
Besides reviewing the scientific and clinical information from Peru on the ingredients and conducting an initial Ames test for mutagenicity, we analysed A4+ for its chemical profile and tested genotoxicity (micronucleus test) and general toxicity (28-day repeated dose).


RESULTS
A4+ and extracts from the three plants provided distinctive chemical fingerprints. A4L contained acetogenins, requiring a second chromatographic method to produce a specific fingerprint. The Ames test proved positive at the highest concentration (5,000 μg/mL) but A4+ showed no evidence of genotoxicity in the more specific mouse micronucleus test. The 28-day repeated dose (general toxicity) study in rats showed no toxicity at 2,000 mg/kg.


CONCLUSIONS
We conclude that under the conditions of these studies, A4+ shows no evidence of toxicity at the levels indicated. A no observed adverse effect level (NOAEL) of 2,000 mg/kg was assigned.
Hugh A
HA
Semple
B Duff
BD
Sloley
José
J
Cabanillas
Andrea
A
Chiu
Steven K H
SK
Aung
Francis H Y
FH
Green
D000818:Animals; D031041:Annona / Q000633:toxicity*; D031213:Cordia / Q000633:toxicity*; D030024:Curcuma / Q000633:toxicity*; D020834:Ethnopharmacology; D008099:Liver / Q000187:drug effects*; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D010568:Peru; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats
D010936:Plant Extracts; C012596:turmeric extract