Genipap (Genipa americana L.) juice intake biomarkers after medium-term consumption.

Genipap (Genipa americana L.) is an exotic fruit largely consumed and well known, in Amazonian pharmacopeia, to treat anemia, measles and uterine cancer. It is also used as a diuretic, digestive, healing, laxative and antiseptic. The aim of this study was to apply an untargeted metabolomics strategy to determine biomarkers of food intake after short-term consumption of genipap juice. Sixteen healthy adult men were administered jenipap juice (250 mL) twice a day for three weeks. Before and after the three weeks of consumption. the subjects drank a control drink, and they consumed a standard diet. Urine was collected after 0-6 h, 6-12 h and 12-24 h. An ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics approach was applied to analyze the urine samples. Principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to highlight experimental differences between groups. The value of the area under the curve (AUC) of the receiver operator characteristic (ROC) curve validated the identified biomarkers. Thirty-one statistically affected urinary metabolites were putatively identified and were mainly related to iridoids family, medium-chain fatty acids, and polyphenols. Also a group of urinary markers including dihydrocaffeic acid (DHCA), 1-(4-hydroxyphenyl)-1,2-propanediol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were established as biomarkers of genipap consumption. Our findings have established a comprehensive panel of changes in the urinary metabolome and provided information to monitor endogenous alterations that are linked to genipap juice intake. These data should be used in further studies to understand the health implications of genipap juice consumption.

Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake.

Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography⁻high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.