Isolation of a Novel Bioactive Fraction from Saffron (Crocus sativus L.) Leaf Waste: Optimized Extraction and Evaluation of Its Promising Antiproliferative and Chemoprotective Effects as a Plant-Based Antitumor Agent

Saffron spice is obtained from the flower’s stigmas through a labor-intensive process. However, other organs (particularly the leaves and tepals) are often regarded as waste. To investigate the health benefits of saffron leaf by-products, an optimized methodology was developed to obtain a phenol-enriched fraction. The main components of this fraction were identified by HPLC-DAD/ESI-MS and the antiproliferative and metal-chelating effects on colon cancer cells (Caco-2) and Fe2+ and Cu2+ ions, respectively, were evaluated. The process involved the extraction of saffron leaves with a 70% hydroalcoholic solution, followed by purification using liquid chromatography. Chemical characterization revealed the presence of several phenolic compounds, including flavonoids (kaempferol, luteolin and quercetin glycosides) as major constituents; whereas, in vitro assays revealed a strong dose-dependent inhibition of cell proliferation. Likewise, the sample exhibited significant iron- and copper-chelating activity, suggesting its potential as a natural chelator to help mitigate the carcinogenic effects of metal accumulation in humans. In summary, this study underscores the potential of the saffron leaf fraction as a promising natural and complementary chemoprotective agent in colorectal cancer. Additionally, these results underscore the value of agricultural by-products, supporting a circular bioeconomy by reducing environmental impact and promoting the sustainable use of natural resources.