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.

A rapid, sensitive electron-capture gas chromatographic procedure for analysis of metabolites of N-methyl,N-propargylphenylethylamine, a potential neuroprotective agent.

INTRODUCTION: N-Methyl,N-propargyphenylethylamine (MPPE) is a novel analog of (-)-deprenyl, a drug prescribed for Parkinson's disease and shown to have neuroprotective and neurorescue properties in a wide variety of in vitro and in vivo models. MPPE is also neuroprotective, but has the advantage over (-)-deprenyl of not being metabolized to amphetamine or N-methylamphetamine. METHOD: In this paper, extractive derivatization with pentafluorobenzenesulfonyl chloride (PFBSC) followed by electron-capture gas chromatography was utilized to study the metabolism of MPPE. RESULTS: The procedure is rapid and reproducible, giving derivatives with excellent chromatographic properties. Using this procedure, it has now been shown that beta-phenylethylamine (PEA), N-methylphenylethylamine (N-methylPEA) and N-propargylphenylethylamine (N-propargylPEA) are formed from MPPE during incubation of this drug with human liver microsomes. Levels of all three metabolites were shown to increase with increasing time of incubation with the microsomes. DISCUSSION: Extractive derivatization with PFBSC followed by electron-capture gas chromatography represents an efficient means of separating and quantitating the metabolites of MPPE, a novel neuroprotective agent.

Metabolism of monoamines in invertebrates: the relative importance of monoamine oxidase in different phyla.

A review of the occurrence of monoamine oxidase activity in invertebrates is presented. In contrast to vertebrates, invertebrates use a variety of enzymatic routes to metabolise monoamines. These routes include N-acetylation, gamma-glutamyl conjugation, sugar conjugation, sulphation, beta-alanyl conjugation as well as oxidative deamination. Some of these enzymatic routes appear to be strictly catabolic whereas others result in metabolites used for structural and pigmentation purposes. The development of the various catabolic routes for monoamines in different groups of invertebrates may be dependent on the physical requirements of the diverse excretory organs used by these animals.