Mango seed kernel (MSK) has demonstrated to be a valuable source of bioactive phenolic compounds with antiproliferative activity against colon cancer cell lines. In this work, a phenolic MSK extract obtained by sequential pressurized liquid extraction (PLE) was submitted to supercritical antisolvent fractionation (SAF) to attain enriched fractions with improved inhibitory effect on HT-29 colon cancer cells. SAF was optimized using a Box-Behnken experimental design and considering as main factors: pressure, percentage of water in the feed extract and feed/sc-CO2 flow rate ratio; selected response variable was the inhibitory cell proliferation (%) and the SAF yield (%) measured in both, raffinates and extracts. The highest inhibitory cell proliferation effect (70.51 ± 1.14%) was obtained in the extract using 50% of water v/v in the feed and 0.0625 feed/sc-CO2 ratio at 15 MPa. This result represents an improvement in the antiproliferative activity by the SAF process compared to the original PLE extract. A targeted phytochemical profiling by LC-q-TOF-MS/MS followed by a multivariate statistical analysis of the observed bioactivity and the chemical composition evidenced the existence of a remarkable variability among the obtained SAF fractions, mainly due to characteristic compounds (e.g., mangiferin, homomangiferin, galloyl methylgallate, ellagic acid and methyl gallate), which might explain the enhanced antiproliferative activity of the optimal SAF extract.
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