The present study investigated the antioxidant activity, metal chelating ability and genoprotective effect of the hydroethanolic extracts of Crocus sativus stigmas (STG), tepals (TPL) and leaves (LV). We evaluated the antioxidant and metal (Fe²⁺ and Cu²⁺) chelating activities of the stigmas, tepals and leaves of C. sativus. Similarly, we examined the genotoxic and DNA protective effect of these parts on rat leukocytes by comet assay. The results showed that TPL contains the best polyphenol content (64.66 µg GA eq/mg extract). The highest radical scavenging activity is shown by the TPL (DPPH radical scavenging activity: IC₅₀ = 80.73 µg/mL). The same extracts gave a better ferric reducing power at a dose of 50 µg/mL, and better protective activity against β-carotene degradation (39.31% of oxidized β-carotene at a 100 µg/mL dose). In addition, they showed a good chelating ability of Fe²⁺ (48.7% at a 500 µg/mL dose) and Cu²⁺ (85.02% at a dose of 500 µg/mL). Thus, the antioxidant activity and metal chelating ability in the C. sativus plant is important, and it varies according to the part and dose used. In addition, pretreatment with STG, TPL and LV significantly (p < 0.001) protected rat leukocytes against the elevation of percent DNA in the tail, tail length and tail moment in streptozotocin- and alloxan-induced DNA damage. These results suggest that C. sativus by-products contain natural antioxidant, metal chelating and DNA protective compounds, which are capable of reducing the risk of cancer and other diseases associated with daily exposure to genotoxic xenobiotics.

Saffron (Crocus sativus L.), known as the world’s most valuable spice, has long been appreciated for its culinary, medicinal, and cultural significance. In recent years, increasing scientific attention has been directed toward its unique phytochemical profile and wide-ranging therapeutic potential. This review provides a comprehensive synthesis of current evidence regarding saffron’s chemical composition, molecular mechanisms of action, pharmacological activities, and safety aspects. The stigmas of saffron contain a rich array of bioactive constituents, notably crocin, crocetin, picrocrocin, and safranal, which collectively contribute to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, hepatoprotective, neuroprotective, anti-obesity, antidiabetic, and anticancer properties. Evidence from in vitro and in vivo models, as well as clinical studies, suggests that saffron primarily exerts its beneficial effects through the modulation of oxidative stress, apoptosis, autophagy, lipid metabolism, and the regulation of key molecular pathways, including the NF-κB, PI3K/Akt/mTOR, and Nrf2/HO-1 pathways. Furthermore, recent advances in nanotechnology-based formulations have demonstrated improved bioavailability and enhanced therapeutic efficacy, thereby opening up promising avenues for clinical applications. While saffron is generally regarded as safe, challenges remain concerning its high cost, limited availability, and variability in quality due to geographic and environmental factors. Collectively, the accumulated body of evidence highlights saffron as a promising natural agent for the prevention and management of chronic diseases. However, further translational and large-scale clinical investigations are needed to fully establish its therapeutic value and optimize its integration into modern pharmacological and nutraceutical strategies.

The most costly spice in the world, Crocus sativus L. (C. sativus), has been used for more than 3,000 years. It has various beneficial applications in a range of fields, including aromas, colorants, and medications, but its usefulness as a food flavoring and coloring ingredient is the highest. Large quantities of by-products from the processing of saffron are typically thrown as unwanted bio-residues. This study’s goal was to assess and compare the nephroprotective effects of hydroethanolic extracts of C. sativus stigmas, tepals, and leaves on gentamicin (GM)-induced nephrotoxicity in rats. For that, we used a biochemical and histological investigation to propose new pharmaceutical valorizations. Based on the biochemical and histological analyses, it is concluded that all the studied parts of C sativus showed a renoprotective effect. Markedly, tepals revealed the most significant reduction of relative liver weight , water intake , plasma creatinine , plasma urea , plasma uric acid , urinary protein and albumin , and renal malondialdehyde (MDA) . In addition, C. sativus tepals caused a significant increase in body weight , urinary creatinine , creatinine clearance , and urinary urea compared with the gentamicin untreated (GM) group. This is confirmed by the histopathological study which shows that treatment with stigmas, tepals, and leaves preserved kidney morphology at the glomerular and tubular cell level. The studied extracts exhibit good recovery potential for nephrotoxicity induced by gentamicin. In order to create potent dietary supplements or phytomedicines, it would also be very interesting to confirm these actions through clinical research.

Background: Saffron (Crocus sativus L.) corms, often discarded as agricultural by-products, are a promising and sustainable source of bioactive metabolites with potential therapeutic relevance. However, their anticancer potential remains largely underinvestigated. Objectives: This study aimed to compare the phytochemical composition of hydroethanolic extracts from fresh (HEEF) and stored (HEES) saffron corms and to evaluate their anticancer effectiveness against colorectal cancer cells. Methods: Phytochemical profiling was performed using HPLC-ESI-QTOF-MS/MS. Cytotoxicity against T84 and SW480 colorectal cancer cell lines was determined by the crystal violet assay. Apoptosis-related protein modulation was assessed by Western blotting. Additionally, molecular docking, molecular dynamics simulations, and MM/GBSA calculations were used to investigate ligand–target binding affinities and stability. Results: Both extracts contained diverse primary and secondary metabolites, including phenolic acids, flavonoids, triterpenoids, lignans, anthraquinones, carotenoids, sugars, and fatty acids. HEES showed higher relative abundance of key bioactive metabolites than HEEF, which was enriched mainly in primary metabolites. HEES showed significantly greater dose-dependent cytotoxicity, particularly against SW480 cells after 24 h (IC₅₀ = 34.85 ± 3.35). Apoptosis induction was confirmed through increased expression of caspase-9 and p53 in T84 cells. In silico studies revealed strong and stable interactions of major metabolites, especially 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid with COX2 and crocetin with VEGFR2. Conclusions: Stored saffron corms possess a richer bioactive profile and show enhanced anticancer effects in vitro compared with fresh saffron corms, suggesting that they may represent a promising source of compounds for the future development of colorectal cancer therapeutics.

Saffron (Crocus sativus L.) corms, often discarded due to their small size, represent a valuable by-product with potential health benefits. This study aims to enhance the value of saffron corms by comparing stored corms (HEES) and fresh corms (HEEF) in terms of chemical composition, antioxidant, genotoxic, and cytotoxic effects. Both corm types were macerated in 50% ethanol, and levels of polyphenols, flavonoids, carotenoids, lycopene, anthocyanins, saponins, and sugars were quantified. Their antioxidant capacity was assessed through DPPH, FRAP, and β-carotene assays, while genotoxicity was evaluated via comet assays, and cytotoxicity was tested on CCD18 normal colon cells using MTT and crystal violet assays. Results showed that stored corms contained higher levels of phenolic compounds (0.781 ± 0.42 µg GAE/mg extract), flavonoids (1.13 ± 0.64 µg QE/mg extract), and carotenoids (27.99 µg β-carotene/g dry matter), compared to fresh corms. HEES also exhibited stronger antioxidant activity with an IC50 of 169.57 µg/mL in the DPPH assay, while HEEF showed an IC50 of 434.37 µg/mL. Both extracts displayed genotoxicity at 50 µg/mL and cytotoxicity on normal colon cells (CCD18) at approximately 300 µg/mL. Stored saffron corms are a rich source of bioactive molecules and exhibit greater antioxidant activity compared to fresh corms. However, both extracts demonstrate genotoxic and cytotoxic effects at higher doses, emphasizing the need for careful evaluation of their potential therapeutic applications. These findings suggest that saffron corms, particularly those that are stored, could be valuable in health-related fields but warrant further investigation. Graphical Abstract

Species of the Opuntia genus are widely recognized for their richness in bioactive metabolites and antioxidant potential, particularly in their cladodes. However, despite increasing interest in cochineal-resistant cultivars, their genotoxic safety remains poorly explored. In this study, the phytochemical composition, antioxidant activity, and genotoxic effects of cladode extracts from three Dactylopius opuntiae-resistant Opuntia species (O. ficus-indica, O. robusta, and O. stricta) collected in eastern Morocco were comparatively evaluated. Hydroethanolic extracts were characterized for their biochemical composition and screened for antioxidant activity using DPPH, β-carotene bleaching, FRAP, and total antioxidant capacity assays. An untargeted UHPLC-Orbitrap MS/MS approach was applied to profile secondary metabolites, while genotoxicity was assessed using the comet assay on rat leukocyte DNA. The three species exhibited distinct phytochemical and antioxidant profiles. O. ficus-indica showed the highest total phenolic and flavonoid contents and the strongest radical scavenging and reducing capacities, whereas O. stricta was particularly rich in ascorbic acid and exhibited the highest total antioxidant capacity. Metabolomic analysis revealed a predominance of phenolic acids and flavonoids, with piscidic acid as a major constituent, along with isorhamnetin derivatives and organic acids. Importantly, none of the extracts induced genotoxic effects compared to the negative control, while all differed significantly from the oxidative damage induced by hydrogen peroxide. Overall, these findings demonstrate the phytochemical richness, antioxidant potential, and genotoxic safety of cochineal-resistant Opuntia cladodes, supporting their sustainable valorization in food, nutraceutical, cosmetic, and agricultural applications.