The study aimed to investigate the effects of acute ingestion of saffron (SAF) on physiological (i.e., heart rate and blood lactate) and perceptual (i.e., ratings of perceived exertion [RPE] and feeling scale) measures in response to a repeated-sprint ability test (RSS) in healthy young males (N = 22; mean ± SD: age, 21.7 ± 1.24 yrs.). All participants completed two experimental trials with a one-week washout period using a double-blind, placebo-controlled, crossover design. In each session, the participants were randomly chosen to receive either a capsule of saffron (300 mg) (SAF session) or a capsule of lactose (PLB session) two hours before performing the RSS.No significant differences (p > 0.05) were found for heart rate, RPE, and feeling scale between the SAF or PLB sessions at pre- and post-RSS. There were no significant changes (p > 0.05) in peak time, total time, fatigue index, and blood lactate in either the SAF or PLB sessions. Acute SAF ingestion did not significantly improve RSS performance nor physiological and perceptual measures in active young males. Future trials should address the topic by using shortened/prolonged higher doses of SAF on biological, physical, physiological, and perceptual responses to acute and chronic exercise.

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn\'s disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD.

Most research on saffron has focused on its composition and beneficial effects, while the culinary perspective to enhance its gastronomic potential remains unexplored. This study aims to define the transfer of the main compounds responsible for color, flavor, and aromatic properties, evaluating three critical variables: temperature (60 °C, 80 °C and 100 °C), infusion time (ranging from 10 to 30 min), and the composition of the medium (water, oil, and water/oil). Samples were analyzed using the LC-QTOF MS/MS and ISO 3632-1:2011 methods. The major compounds were crocins, including trans-crocin and picrocrocin. Among the flavonoids, kaempferol 3-O-sophoroside stands out. Regarding extraction conditions, crocins, glycoside flavonoids, and picrocrocin were enhanced in water, the former in 100% water and at low temperatures, while picrocrocin proved to be the most stable compound with extraction favored at high temperatures. The variable with the greatest incidence of picrocrocin isolation seemed to be the concentration of water since water/oil compositions reported higher concentrations. Safranal and kaempferol were enriched in the oil phase and at lower temperatures. This study provides a chemical interpretation for the appropriate gastronomic use of saffron according to its versatility. Finally, the determination of safranal using the ISO method did not correlate with that obtained using chromatography.

Saffron, renowned for its aroma and flavor, is susceptible to adulteration due to its high value and demand. Current detection methods, including ISO standards, often fail to identify specific adulterants such as safflower or turmeric up to 20% (w/w). Therefore, the quest continues for robust screening methods using advanced techniques to tackle this persistent challenge of safeguarding saffron quality and authenticity. Advanced techniques such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), with its molecular specificity and high sensitivity, offer promising solutions. Samples of pure saffron and saffron adulterated with safflower and turmeric at three inclusion levels (5%, 10%, and 20%) were analyzed without prior treatment. Spectral analysis revealed distinct signatures for pure saffron, safflower, and turmeric. Through principal component analysis (PCA), TOF-SIMS effectively discriminated between pure saffron and saffron adulterated with turmeric and safflower at different inclusion levels. The variation between the groups is attributed to the characteristic peaks of safflower and the amino group peaks and mineral peaks of saffron. Additionally, a study was conducted to demonstrate that semi-quantification of the level of safflower inclusion can be achieved from the normalized values of its characteristic peaks in the saffron matrix.

UNASSIGNED: Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity.
UNASSIGNED: PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 μM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC50), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement.
UNASSIGNED: In vitro studies showed that TSC at a concentration of 7.81 μM and BMPC at concentrations of 3.9, 7.81, and 15.62 μM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC.
UNASSIGNED: TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.

Saffron (Crocus sativus) floral by-products are a source of phenolic compounds that can be recovered and used in the nutraceutical, pharmaceutical, or cosmetic industries. This study aimed to evaluate the phenolic compounds\' extraction using green extraction techniques (GETs) in saffron floral by-products and to explore the influence of selected extraction techniques on the phytochemical composition of the extracts. Specifically, ultrasound-assisted extraction (UAE), subcritical water extraction (SWE), and deep eutectic solvents extraction (DESE) were used. Phenolic compounds were identified with (HR) LC-ESI-QTOF MS/MS analysis, and the quantitative analysis was performed with HPLC-PDA. Concerning the extraction techniques, UAE showed the highest amount for both anthocyanins and flavonoids with 50:50% v/v ethanol/water as solvent (93.43 ± 4.67 mg/g of dry plant, dp). Among SWE, extraction with 96% ethanol and t = 125 °C gave the best quantitative results. The 16 different solvent mixtures used for the DESE showed the highest amount of flavonoids (110.95 ± 5.55-73.25 ± 3.66 mg/g dp), while anthocyanins were better extracted with choline chloride:butane-1,4-diol (16.0 ± 0.80 mg/g dp). Consequently, GETs can be employed to extract the bioactive compounds from saffron floral by-products, implementing recycling and reduction of waste and fitting into the broader circular economy discussion.

Plants are an important source of essential bioactive compounds that not only have a beneficial role in human health and nutrition but also act as drivers for shaping gut microbiome. However, the mechanism of their functional attributes is not fully understood despite their significance. One such important plant is Crocus sativus, also known as saffron, which possesses huge medicinal, nutritional, and industrial applications like food and cosmetics. The importance of this plant is grossly attributed to its incredible bioactive constituents such as crocins, crocetin, safranal, picrocrocin, and glycosides. These bioactive compounds possess a wide range of therapeutic activities against multiple human ailments. Since a huge number of studies have revealed negative unwanted side effects of modern-day drugs, the scientific communities at the global level are investigating a large number of medicinal plants to explore natural products as the best alternatives. Taken into consideration, the available research findings indicate that saffron has a huge scope to be further explored to establish alternative natural-product-based drugs for health benefits. In this review, we are providing an update on the role of bioactive compounds of saffron as therapeutic agents (human disorders and antimicrobial activity) and its nutritional values. We also highlighted the role of omics and metabolic engineering tools for increasing the content of key saffron bioactive molecules for its mass production. Finally, pre-clinical and clinical studies seem to be necessary to establish its therapeutic potential against human diseases.

Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.

This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.

Several limitations in genetic engineering interventions in saffron exist, hindering the development of genetically modified varieties and the widespread application of genetic engineering in this crop. Lack of genome sequence information, the complexity of genetic makeup, and lack of well-established genetic transformation protocols limit its in planta functional validation of genes that would eventually lead toward crop optimization. In this study, we demonstrate agro infiltration in leaves of adult plants and whole corm before sprouting are suitable for transient gene silencing in saffron using Tobacco Rattle Virus (TRV) based virus-induced gene silencing (VIGS) targeting phytoene desaturase (PDS). Silencing of PDS resulted in bleached phenotype in leaves in both methods. TRV-mediated VIGS could be attained in saffron leaves and corms, providing an opportunity for functional genomics studies in this expensive spice crop.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12298-024-01459-0.