Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc.

J Pharm Pharmacol. 2018 Jul;70(7):976-984. doi: 10.1111/jphp.12918. Epub 2018 Apr 6. Makhuvele R1,2, Foubert K3, Apers S3, Pieters L3, Verschaeve L4,5, Elgorashi E1,2. Author information 1 Toxicology and Ethnoveterinary Medicine, ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa. 2 Department of Paraclinical Sciences, University of Pretoria, Onderstepoort, South Africa. 3 Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp-Wilrijk, Belgium. 4 Toxicology, Scientific Institute of Public Health, Brussels, Belgium. 5 Department of Biomedical Sciences, University of Antwerp, Antwerp-Wilrijk, Belgium. Abstract OBJECTIVES: Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to possess antitumoural properties. Preliminary screening showed that the crude methanolic leaf extract had strong antimutagenic effects against aflatoxin B1 -induced mutagenicity. The aim of this study was to isolate and evaluate the antimutagenic properties of the active constituents from M. caffra. METHODS: Different chromatographic, spectroscopic and spectrometric techniques were used for the isolation and identification of the antimutagenic constituents. The antimutagenic effect of the extract and compounds was evaluated using Ames, Vitotox and Comet assays. KEY FINDINGS: Bioassay-guided fractionation of the methanolic leaf extract yielded two antimutagenic compounds identified as (+)-crotepoxide and 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene. Crotepoxide had strong antimutagenicity in the Vitotox assay with an IC50 value of 131 μg/ml. 5,6-Diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene showed strong antimutagenic activity in the Ames assay with an IC50 value of 348.9 μg/plate and no antimutagenic activity in the Vitotox test. Furthermore, the compound was able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing the proteins involved in transcription. CONCLUSIONS: Crotepoxide and 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene have the potential to mitigate the risks arising from consumption of aflatoxin B1 -contaminated food and feed. © 2018 Royal Pharmaceutical Society. KEYWORDS: (+)-crotepoxide ; Monanthotaxis caffra ; 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene; aflatoxin B1; antimutagenicity PMID: 29633259 DOI: 10.1111/jphp.12918