In vitro cytotoxic activity of six Syzygium leaf extracts as related to their phenolic profiles: An untargeted UHPLC-QTOF-MS approach

Untargeted metabolomics was used in this study to discriminate the phenolic fingerprints of six Syzygium species. This approach resulted in the annotation of 441 compounds that belong to different phenolic classes, such as flavonoids, lignans, stilbenes, tyrosols, alkylphenols, and phenolic acids. Multivariate data analysis unraveled the main differences between the studied species. S. paniculatum and S. aqueum were the richest sources in terms of phenolic compounds, cumulatively amounting to 355.3 and 266.4 mg/g dry matter, respectively. Nevertheless, S. jambos showed reduced amounts of phenolics, when compared with other species. The biological activity of Syzygium leaf extracts was assessed on MCF-7 breast adenocarcinoma and MDA-MB-231 breast cancer cell lines. Potent estrogenic activity was detected using the SRB assay on MCF-7. This activity may be ascribable to the presence of phenolic compounds miming phytoestrogens such as lignans, stilbenes, and isoflavonoids in the investigated Syzygium extracts. By examining the biological effect of Syzygium extracts against MDA-MB-231 cell lines, the Syzygium gratum leaf extract exhibited the strongest inhibition, with IC50 = 19.4 µg/mL, followed by S. paniculatum (IC50 = 50.9 µg/mL). However, the Syzygium gratum leaf extract showed a potent cytotoxic effect on normal human skin fibroblasts, HSF (IC50 = 1.24 µg/mL), assuming a nonselective cytotoxic effect. On the other hand, other studied Syzygium leaves proved as safe nutraceuticals (IC50 ≥ 100 µg/mL) on HSF cell lines. Our study suggested a possible implication of Syzygium malaccense and Syzygium aqueum leaves as potential estrogenic candidates in relation to their health-promoting phenolic constituents.