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We investigated the effects of PEG-induced drought on the antioxidative mechanisms of Crocus sativus L. and the mitigating effects of PEN on drought tolerance. Contents of H₂O₂ and MDA in fibrous roots were considerably lower than those in leaves and were attenuated by PEN pretreatment. Activities of CAT, SOD, and POX were significantly higher in fibrous roots than in leaves. Among antioxidative enzymes, POX activity in fibrous roots was 600–2000-fold higher than that in leaves. The increase in CAT and SOD activities under the influence of PEN in the fibrous roots is the main reason for the decrease in MDA levels and highlights the important role of this organ in the response to drought stress. A somewhat similar increase in CAT activity was also observed in the leaves under drought conditions due to PEN. Under drought, PEN led to a significant increase in carotenoid content and an elevated ratio of Chl a to Chl b in the leaves. However, in spite of the higher content of non-enzymatic antioxidants in leaves than in fibrous roots, the lower MDA levels in fibrous roots indicated greater efficiency of antioxidative enzymes in controlling membrane lipid peroxidation. In conclusion, the results demonstrate that PEN can mitigate oxidative damage in saffron under drought conditions by enhancing the activity of SOD (up to 275%) and CAT (up to 189%) and by increasing proline content (up to 50%) in fibrous roots.

Saffron (Crocus sativus L.) and its main constituents, i.e., crocin and crocetin, are natural carotenoid compounds, which have been reported to possess a wide spectrum of properties and induce pleiotropic anti-inflammatory, anti-oxidative, and neuroprotective effects. An increasing number of experimental, animal, and human studies have investigated the effects and mechanistic pathways of these compounds in order to assess their potential therapeutic use in ocular diseases (e.g., in age related macular degeneration, glaucoma, and diabetic maculopathy). This narrative review presents the key findings of published clinical studies that examined the effects of saffron and/or its constituents in the context of ocular disease, as well as an overview of the proposed underlying mechanisms mediating these effects.

Saffron is a unique spice obtained by drying stigmas of saffron flowers ( Crocus sativus L.). Due to its high price, economically motivated adulteration occurs relatively often. The presented study aimed to develop an effective strategy for the detection of the following potential botanical adulterants used for a saffron substitution or dilution: safflower ( Carthamus tinctorius L.), calendula ( Calendula officinalis L.) , turmeric ( Curcuma longa L.), achiote ( Bixa orellana L.), red pepper ( Capsicum spp.), mountain arnica ( Arnica montana L.), beet ( Beta vulgaris L.), and pomegranate ( Punica granatum L.). A non-target screening strategy based on ultra-high performance reverse-phase liquid chromatography coupled to tandem high-resolution mass spectrometry (UHPLC-HRMS/MS) was employed for the analysis of an aqueous ethanol plant extract. By using multivariate statistical methods, principal components analysis (PCA), and partial least squares discriminant analysis (PLS-DA), for processing the generated “chemical fingerprints,” metabolites unique to the investigated plants could be identified. To enable routine saffron authenticity control by target screening, an internal spectral database was developed; currently, it involves 82 unique markers. In this way, the detection addition as low as 1% ( w/w ) of all analyzed botanical adulterants in admixture with saffron was possible. The developed method was used to control 7 saffron powder samples from the Czech market, and none of the monitored adulterants were confirmed.

Saffron can be infected with pathogenic fungi that cause corm rot as it grows and multiplies, which can reduce the quality and yield of saffron. Corm rot has become one of the most serious diseases of saffron. In this study, rhizosphere bacteria were isolated from saffron rhizosphere soil, and bacteria exhibiting antagonistic effects against corm rot pathogenic fungi were screened using in vitro plate co-culture assays and dual-compartment agar plate systems. Selected strains were further evaluated for hydrolase activity determination and PGP potential assessment. Among them, Bacillus velezensis showed the best disease resistance activity. The degradative enzyme production and some beneficial characteristics of Bacillus velezensis for plant growth promotion were evaluated. It was found that Bacillus velezensis possesses nitrogen fixing, NH 3 -producing, IAA production, and ACC-deaminating enzymes. The whole genome sequence of this strain was annotated and analyzed. The genome of Bacillus velezensis consists of a circular chromosome of 3,908,025 bp base pairs, with a guanine and cytosine content of 46.64%. There are 3737 protein-coding genes, including 86 tRNA genes, 27 rRNA genes, and 85 sRNA genes. The genome also contains four genomic islands, two pre-phages, and one transposon. The prediction of the secondary metabolic accumulation gene cluster demonstrated that the genome sequence of ZGE166 encodes 12 gene clusters involved in the synthesis of secondary metabolites, including macrolactin H, bacillaene, fengycin, difficidin, and bacillibactin. In summary, strain ZGE166 Bacillus velezensis has the potential to be developed as a biological agent.

This study explores the antimicrobial activity of three principal bioactive constituents of Crocus sativus L.—safranal, crocin, and crocetin—using a simplex-centroid mixture design to evaluate their individual and synergistic effects. Twelve formulations were tested against Staphylococcus aureus , Escherichia coli , Candida albicans , and Geotrichum candidum . Minimum inhibitory concentrations (MICs) were determined via microdilution assays, and the results were fitted using special cubic regression models. The models exhibited strong predictive accuracy (R 2 = 0.97–0.99). Safranal showed the highest individual activity against S. aureus (σ 1 = 169.77, p = 0.0053), while crocin exerted the strongest effect on E. coli (σ 2 = 166.63, p < 0.0001). Significant synergistic interactions were observed between crocin and crocetin for both bacterial strains (σ 23 = −290.34 for S. aureus ; −170.28 for E. coli ). Ternary mixtures displayed superior efficacy compared to single compounds, producing the lowest MIC values across all pathogens. The optimal antibacterial formulation—33.31% safranal, 33.29% crocin, and 33.39% crocetin—yielded MICs of 41.14% (v/v) (predicted) and 39.5% ± 0.75% (v/v) (experimental) against E. coli . Against S. aureus , a blend of 27% safranal, 33% crocin, and 38% crocetin resulted in a predicted MIC of 42.15% (v/v) , confirmed experimentally at 38.13% ± 1.33% (v/v) . For G. candidum , the optimized mixture reached MIC values of 9.13% (v/v) (predicted) and 10.24% ± 2.05% (v/v) (observed). These findings demonstrate that synergistic combinations of saffron-derived metabolites markedly enhance antimicrobial potency. Moreover, mixture design modeling emerges as an effective predictive and optimization strategy for developing reproducible, plant-based antimicrobial formulations targeting antibiotic resistance.

Cold plasma is an emerging non-thermal processing technology that could fulfill the food industry’s need for decontamination purposes without compromising the quality if optimized in terms of plasma parameters, including feed gases, voltage, and exposure time. Different food matrices require specialized optimized processes due to the interactions between plasma and the food. In the present study, the response surface methodology was applied to optimize the radiofrequency low-pressure cold plasma processing of saffron (Crocus sativus L. stigmas.) with the aim of achieving the highest decontamination level with the least harm to metabolites. The effects of the treatment time, power, and three gas mixtures (X, Y, and Z) consisting of air, oxygen, and argon on 22 responses related to microbial load and quality of saffron were evaluated in 42 experiments. Eleven critical responses that determine the final quality of saffron were considered to calculate the desirable function as a comprehensive approach for optimization. Analyses showed that all factors significantly affected the desirable function, and the fitted linear model was significant. The optimal condition was determined as an RF power of 76 W for 26 min using the “Y” gas mixture, which reduced the total microorganisms, coliforms, Escherichia coli, molds, and yeast by 5.75, 6.71, 6.07, and 4.00 log CFU g−1 respectively. The optimal condition preserved saffron quality within category I of the ISO specification No. 3632-1. The experimental values were in accordance with the predicted values. Optical emission spectroscopy revealed that the main plasma reactive species were Ar+ species, monoatomic oxygen, O2+, O+ ions, excited N2 species, and N2+ ions. The temperature of the samples after treatment was in the range of 40–44 °C. Scanning electron microscopy of the saffron threads indicated surface etching. Our findings showed that saffron was disinfected without substantial harm to its appearance and metabolites by applying appropriate plasma treatment.

Cervical cancer ranks as the fourth most common malignancy among women worldwide. It is closely associated with the dysregulation of numerous genes and signaling pathways. Conventional treatments for cervical cancer often lead to adverse side effects and the development of drug resistance. In this study, network pharmacology was employed to identify the active components and potential targets of Crocus sativus L. Molecular docking and surface plasmon resonance analyses were used to validate the interaction between lauric acid and a key target. Lauric acid-modified gold nanoparticles (Au@LA) were synthesized and characterized. Twenty-three active components and 819 potential targets of Crocus sativus L. were identified, with PTGS2 being the main target. Au@LA selectively inhibited HeLa cell proliferation, induced apoptosis, downregulated SLC7A11 and GPX4, and modulated oxidative stress markers. In macrophages, Au@LA shifted M2 polarization to the pro-inflammatory M1 phenotype and modulated the PGE2/EP2/cAMP-PKA signaling axis. Our findings indicate that Au@LA has dual anti-cervical cancer properties through inducing ferroptosis in HeLa cells and reprogramming macrophage polarization. It shows promise as a candidate for natural product-based nanomedicine in cervical cancer therapy, potentially opening new avenues for more effective and targeted treatments in the future.

Saffron is the most expensive spice in the world. In addition to its culinary utilization, this spice is used for medicinal purposes such as in pain management. In this study, the analgesic activity of Crocus sativus stigma extract (CSSE) was evaluated in rodents and its possible physiological mechanism was elucidated. The anti-nociceptive effect of CSSE was evaluated using three animal models (hot plate, writhing, and formalin tests). The analgesic pathways involved were assessed using various analgesia-mediating receptors antagonists. The oral administration of CSSE, up to 2000 mg/kg, caused no death or changes in the behavior or in the hematological and biochemical blood parameters of treated animals nor in the histological architecture of the animals’ livers and kidneys. CSSE showed a central, dose-dependent, anti-nociceptive effect in response to thermal stimuli; and a peripheral analgesic effect in the test of contortions induced by acetic acid. The dual (central and peripheral) analgesic effect was confirmed by the formalin test. The anti-nociceptive activity of CSSE was totally or partially reversed by the co-administration of receptor antagonists, naloxone, atropine, haloperidol, yohimbine, and glibenclamide. CSSE influenced signal processing, by the modulation of the opioidergic, adrenergic, and muscarinic systems at the peripheral and central levels; and by regulation of the dopaminergic system and control of the opening of the ATP-sensitive K+ channels at the spinal level. The obtained data point to a multimodal mechanism of action for CSSE: An anti-inflammatory effect and a modulation, through different physiological pathways, of the electrical signal generated by the nociceptors. Further clinical trials are required to endorse the potential utilization of Moroccan saffron as a natural painkiller.

Saffron (Crocus sativus L.) has been traditionally used in food preparation and as a medicinal plant. It currently has numerous therapeutic properties attributed to it, such as protection against ischemia, as well as anticonvulsant, antidepressant, anxiolytic, hypolipidemic, anti-atherogenic, anti-hypertensive, antidiabetic, and anti-cancer properties. In addition, saffron has remarkable beneficial properties, such as anti-apoptotic, anti-inflammatory and antioxidant activities, due to its main metabolites, among which crocin and crocetin stand out. Furthermore, increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, both in experimental models and in clinical studies in patients. Currently, saffron supplementation is being tested for ocular neurodegenerative pathologies, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration and glaucoma, among others, and shows beneficial effects. The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases. This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

The propagation of Crocus sativus L. relies exclusively on corm multiplication. As underground storage organs, corms are susceptible to a wide range of pathogens, environmental stresses, and diseases, making traditional propagation methods often ineffective with the loss of valuable material. In vitro propagation offers an alternative for the saffron culture under controlled conditions. In particular, the innovative application of the Temporary Immersion System (TIS) represents a technological advancement for enhancing biomass production with a reduction in operational costs. The current study utilized the Plantform™ bioreactor to propagate in vitro saffron corms from the ‘Abruzzo’ region (Italy), integrating machine learning models to assess its performance. The evaluation of saffron explants after 30, 60, and 90 days of culture showed a marked improvement in growth and microcorm production compared to conventional in vitro culture on semisolid medium, supported by the machine learning analysis. Indeed, the Random Forest algorithm revealed a predictive accuracy with an R2 value of 0.81 for microcorm number, showcasing the capability of machine learning models to forecast propagation outcomes effectively. These results confirm that applying TIS in saffron culture could lead to economically viable, large biomass production within a controlled environment, irrespective of seasonality. This study represents the first endeavor to use TIS technology to enhance the in vitro propagation of saffron in conjunction with machine learning, suggesting an innovative approach for cultivating high-value crops like saffron.