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Background  Saffron or stigmas of  Crocus sativus  L. is one of the most valuable food products with interesting health-promoting properties.  C. sativus  has been widely used as a coloring and flavoring agent. Stigmas secondary metabolites showed potent cytotoxic effects in previous reports.    Methods  The present study investigated the chemical composition and the cytotoxic effect of Ukrainian saffron crude extracts and individual compounds against melanoma IGR39, triple-negative breast cancer MDA-MB-231, and glioblastoma U-87 cell lines in vitro using MTT assay. Several bioactivity in vitro assays were performed. The chemical profile of the water and hydroethanolic (70%, v/v) crude extracts of saffron stigmas was elucidated by HPLC-DAD analysis.    Results  Seven compounds were identified including crocin, picrocrocin, safranal, rutin, apigenin, caffeic acid, ferulic acid. Crocin, picrocrocin, safranal, rutin, and apigenin were the major active constituents of Ukrainian  C. sativus  stigmas. The hydroethanolic extract significantly reduced the viability of MDA-MB-231 and IGR39 cells and the effect was more potent in comparison with the water extract. However, the water extract was almost 5.6 times more active against the U-87 cell line (EC 50  of the water extract against U-87 was 0.15 ± 0.02 mg/mL, and EC 50  of the hydroethanolic extract was 0.83 ± 0.03 mg/mL). The pure compounds, apigenin, and caffeic acid also showed high cytotoxic activity against breast cancer, melanoma, and glioblastoma cell lines. The screening of the biological activities of stigmas water extract (up to 100 μg/mL) including anti-allergic, anti-virus, anti-neuraminidase, and anti-inflammatory effects revealed its inhibitory activity against neuraminidase enzyme by 41%.    Conclusions  The presented results revealed the qualitative and quantitative chemical composition and biological activity of  Crocus sativus  stigmas from Ukraine as a source of natural anticancer and neuraminidase inhibitory agents. The results of the extracts’ bioactivity suggested future potential applications of saffron as a natural remedy against several cancers.

Bio-guided bioactive profiling and HPLC-DAD fingerprinting of Ukrainian saffron (Crocus sativus stigmas): moving from correlation toward causation