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

Abstract

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 (EC50 of the water extract against U-87 was 0.15 ± 0.02 mg/mL, and EC50 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.

Model implementation of the legal regulation on medicinal plant cultivation for pharmaceutical purposes. Case study of Crocus sativus cultivation in Ukraine

“…However, officially published data was not found, only oral reports. Our research (Mykhailenko et al, 2021a) has shown cytotoxic (MDA-MB-231 and IGR39 cells line) and neuraminidase inhibitory activities of saffron from Ukraine.…”

Pharmacological Potential and Chemical Composition of Crocus sativus Leaf Extracts

“…Flavonoids are potent antiproliferative and cytotoxic agents [ 37 ]. Their composition and concentration significantly contributed to the cytotoxic activity in Crocus extracts [ 38 ].…”

Comparative analysis of apocarotenoids and phenolic constituents of Crocus sativus stigmas from 11 countries: Ecological impact

“…[ 29 ] These data also report the antioxidant properties of saffron by total phenolic content, radical scavenging activity, and ferric reducing antioxidant power in stigmas. [ 13,23,24,29 ] Thus, the published articles on saffron chemical composition are limited to several countries and the identification of mainly kaempferol and quercetin derivatives; the components quantitative content and their comparison are not everywhere, and the assessment of the influence of environmental factors is also given only for several countries. Various environmental factors, such as the geographical location of the plant at a different altitude, the amount of rainfall, seasonal variation, and different levels of exposure to sunlight, and in addition, the type of soil, have some influence on the phytochemical profile of plants.…”

“…[ 28 ] Previously, we found rutin, apigenin, caffeic acid, and ferulic acid in the stigma crude extracts of Crocus from Ukraine. [ 29 ] These data also report the antioxidant properties of saffron by total phenolic content, radical scavenging activity, and ferric reducing antioxidant power in stigmas. [ 13,23,24,29 ] Thus, the published articles on saffron chemical composition are limited to several countries and the identification of mainly kaempferol and quercetin derivatives; the components quantitative content and their comparison are not everywhere, and the assessment of the influence of environmental factors is also given only for several countries.…”

“…The method of obtaining saffron extracts and antibacterial assay has been described previously. [29,72] Briefly, crushed C. sativus stigma (Ukraine, Kherson) was macerated with hot distilled water (80°C)/80% ethanol (1:100), kept in a dark place for 24 h, then the extract was filtered. The maceration was repeated two more times with the residue under the same conditions.…”