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Applied Sciences
Volume 15
Issue 13
10.3390/app15137376
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Raúl Sánchez-Vioque
1,2,
Julio Girón-Calle
3,
Manuel Alaiz
3,
Javier Vioque-Peña
3,
Adela Mena-Morales
2,
Esteban García-Romero
2,
Lourdes Marchante-Cuevas
2 and
Gonzalo Ortiz de Elguea-Culebras
2,*
1
Institute of Human Resources for Science and Technology (INCRECYT), Science and Technology Park Foundation from Castilla—La Mancha, Paseo de la Innovación 1, 02006 Albacete, Spain
2
Regional Institute of Agri-Food and Forestry Research and Development of Castilla-La Mancha (IRIAF), N-310, 19, 13700 Tomelloso, Spain
3
Fat Institute (IG), Spanish National Research Council (CISC), Pablo de Olavide University, Ctra. de Utrera, Km. 1, 41012 Sevilla, Spain
*
Author to whom correspondence should be addressed.
Appl. Sci. 2025, 15(13), 7376; https://doi.org/10.3390/app15137376 (registering DOI)
Submission received: 12 May 2025 / Revised: 19 June 2025 / Accepted: 26 June 2025 / Published: 30 June 2025
(This article belongs to the Special Issue Advances in Natural Products: Extraction, Bioactivity, Biotransformation, and Applications)
Versions Notes

Featured Application

The phenolic-enriched fraction of saffron leaf demonstrates strong potential as an anticancer and chemoprotective agent, due to its antioxidant, antiproliferative and metal-chelating properties, supporting its application in complementary cancer therapies and the development of health-promoting nutraceuticals.

Abstract

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.
Keywords: circular bioeconomy; antiproliferative; colorectal cancer; metal-chelating; phenolic content; saffron leave waste circular bioeconomy; antiproliferative; colorectal cancer; metal-chelating; phenolic content; saffron leave waste

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MDPI and ACS Style

Sánchez-Vioque, R.; Girón-Calle, J.; Alaiz, M.; Vioque-Peña, J.; Mena-Morales, A.; García-Romero, E.; Marchante-Cuevas, L.; Ortiz de Elguea-Culebras, G. 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. Appl. Sci. 2025, 15, 7376. https://doi.org/10.3390/app15137376

AMA Style

Sánchez-Vioque R, Girón-Calle J, Alaiz M, Vioque-Peña J, Mena-Morales A, García-Romero E, Marchante-Cuevas L, Ortiz de Elguea-Culebras G. 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. Applied Sciences. 2025; 15(13):7376. https://doi.org/10.3390/app15137376

Chicago/Turabian Style

Sánchez-Vioque, Raúl, Julio Girón-Calle, Manuel Alaiz, Javier Vioque-Peña, Adela Mena-Morales, Esteban García-Romero, Lourdes Marchante-Cuevas, and Gonzalo Ortiz de Elguea-Culebras. 2025. "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" Applied Sciences 15, no. 13: 7376. https://doi.org/10.3390/app15137376

APA Style

Sánchez-Vioque, R., Girón-Calle, J., Alaiz, M., Vioque-Peña, J., Mena-Morales, A., García-Romero, E., Marchante-Cuevas, L., & Ortiz de Elguea-Culebras, G. (2025). 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. Applied Sciences, 15(13), 7376. https://doi.org/10.3390/app15137376

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