OLIVE LEAF EXTRACTS: CHARACTERIZATION OF PHENOLIC CONTENT, ANTIOXIDANT ACTIVITY, INFLUENCE OF IN VITRO DIGESTION, AND CYTOTOXIC POTENTIAL ON COLON AND LIVER CANCER CELLS

INTRODUCTION AND OBJECTIVE: Cancer incidence and mortality rates are worrying. Colorectal cancer is now the third most frequent and second most deadly cancer, whereas liver cancer is the third most lethal, despite being the sixth most prevalent. In this sense, less aggressive treatment alternatives and preventative measures are being investigated based on the anticancer potential of plant-derived bioactive compounds (BC) and potential interactions between them. Olive tree cultivation and the olive oil industry, predominantly located in the Mediterranean region, are on the rise in Brazil. This industry generates a substantial number of by-products and waste materials, most of which lack practical applications but are sources of BC, such as olive leaves. Olive leaf is a source of BC with antioxidant activity and has demonstrated anticancer properties. Investigating Brazilian Olive Leaf Extracts (BOLE), which are currently understudied in terms of bioactive composition and health activities, may allow the exploration of this complex plant matrix in cancer cells. The use of an in vitro digesting approach allows the exploitation of its potential, considering the transformations that occurred post-intake. This study aims to characterize the phenolic composition and antioxidant activity of the BOLE of two cultivars (Coratina and Picual) and their digested fractions, determine the most effective method of extraction, and evaluate the antitumoral activity. MATERIAL AND METHODS: The extracts obtained by infusion and ultrasound-assisted extraction were subjected to simulated gastrointestinal in vitro digestion by the INFOGEST method and evaluated for total phenolic content (Folin-Ciocalteu) and antioxidant potential (DPPH and ABTS). The characterization of polyphenols from BOLE and digested fractions was carried out by UHPLC-ESI-MS/MS. Colon adenocarcinoma (HT29 and HCT116) and hepatocellular carcinoma cells (HepG2) were exposed to different concentrations of olive leaf extracts, and the digested fractions for 24 and 48h was analyzed for viability by the Alamar Blue and Trypan Blue assays. RESULTS AND CONCLUSION: Partial results showed higher phenolic content for extracts obtained by infusion; all extracts exhibited an abundance of polyphenols (107–187 mg/kg), mainly secoiridoids and flavonoids. The in vitro digestion showed effects on the phenolic profile, with changes and reductions in the profile of the identified compounds, lower recovery in the gastric phase, and an increase at the enteral phase, with bioavailability ≥30% and a majority presence of the metabolite ligstroside aglycone derivative. The BOLE has the capacity to decrease the viability of HT29, HCT116, and HepG2 cells. These findings show the possibility of exploiting this residue as a plant matrix source of bioactive polyphenols, elucidate how digestion affects the bioactive content of this plant matrix, and suggest potential cytotoxic action in cancer cells.