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Journal of Complementary and Integrative Medicine

Editor-in-Chief: Lui, Edmund

Ed. by Ko, Robert / Leung, Kelvin Sze-Yin / Saunders, Paul / Suntres, PH. D., Zacharias

CiteScore 2017: 1.41

SCImago Journal Rank (SJR) 2017: 0.472
Source Normalized Impact per Paper (SNIP) 2017: 0.564

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Toxicology of a Peruvian botanical remedy to support healthy liver function

Hugh A. Semple / B. Duff Sloley / José Cabanillas / Andrea Chiu / Steven K. H. Aung / Francis H. Y. Green
  • Corresponding author
  • Snyder Institute for Chronic Diseases, Faculty of Medicine, University of Calgary, 3280 Hospital Drive N.W., Calgary, AB, Canada T2N 4Z6
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Published Online: 2016-04-21 | DOI: https://doi.org/10.1515/jcim-2015-0054


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.

This article offers supplementary material which is provided at the end of the article.

Keywords: Annona muricata; Cordia lutea; Curcuma longa; herbal medicine; liver disease; toxicity testing


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About the article

aHugh A. Semple and B. Duff Sloley contributed equally to this work.

Received: 2015-07-17

Accepted: 2016-02-10

Published Online: 2016-04-21

Published in Print: 2016-06-01

Citation Information: Journal of Complementary and Integrative Medicine, Volume 13, Issue 2, Pages 163–173, ISSN (Online) 1553-3840, ISSN (Print) 2194-6329, DOI: https://doi.org/10.1515/jcim-2015-0054.

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