The bioactive properties of underutilized corks such as Quercus cerris cork and planted
Quercus suber cork in the Eastern Mediterranean are not well-known but are crucial in developing
lignocellulosic biorefineries. To assess their biological potential, hydroethanolic cork extracts of Quercus
cerris and Quercus suber were analyzed for phenolic composition, antioxidant, antiproliferative,
antimicrobial activities, and hepatoxicity, as well as NO-production inhibition. Here, we show that
a mild hydroethanolic extraction of Q. cerris and Q. suber corks yielded 3% phenolic extracts. The
phenolic composition was similar in both cork extracts, with phenolic acids and ellagitannins as the
primary compounds. The bioactivity of hydroethanolic cork extracts from Q. cerris surpassed that of
Q. suber and showed effectiveness against all cancer cell lines tested. This first comprehensive study
on the bioactivities of different corks involves detailed characterizations of phenolic compounds of
cork extracts using UPLC-DAD-ESI/MSn, evaluations of the antioxidant properties with TBARS and
OxHLIA methods, evaluation of antiproliferative activity against gastric (AGS), lung (NCI-H460),
colon (CaCo2), and breast cancer (MCF7) cell lines, as well as evaluations of hepatotoxicity and
NO-production inhibition. The findings from this study will help bolster the potential of using
underutilized cork-rich barks as a valuable resource in bark-based biorefineries.