Search Results (118)

Crocus sativus L. (saffron), a sterile geophyte of the Iridaceae family, has been traditionally used in culinary and medicinal practices and is currently gaining attention as a source of pharmacologically active metabolites. The main bioactive compounds (BACs) of saffron, crocin, crocetin, picrocrocin, and safranal, are associated with a wide range of biological activities, including anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, antiproliferative, and antidiabetic properties, among others. This review aims to comprehensively and critically summarize the preclinical and clinical evidence for saffron-derived BACs in the context of the most prevalent non-communicable diseases. A literature search of the main scientific databases was conducted to identify peer-reviewed articles on neurodegenerative disorders, cancer, cardiovascular diseases, and diabetes mellitus, with additional topics on ethnopharmacology, phytochemistry, safety, and toxicity. The mechanistic findings include anti-inflammatory, immunomodulatory, antioxidant, antiproliferative, and neuroprotective effects, mediated by activation of the Nrf2 pathway and inhibition of NF-κB. Eligibility criteria were applied, excluding publications focused primarily on food, cosmetics, or technological applications, to prioritize mechanistic and therapeutic endpoints. The findings suggest that BACs from saffron extracts have promising disease-modifying properties and symptom-relieving actions, especially in the case of neurologic disorders, mild cognitive impairment, and some models of metabolic and oncological diseases. Nevertheless, the current variability in study design, dosage, standardization of plant extracts, and sample size limits a conclusive clinical application. More carefully designed studies with a representative number of cases and well-defined plant preparations are needed to validate efficacy, establish structure-activity relationships, and define the prevention and therapeutic potential of saffron in evidence-based pharmacotherapy. Full article

Saffron (Crocus sativus L.) is widely cultivated for the spice obtained from the stigmas, while the remaining floral biomass is discarded as biowaste. Accessing the phytochemical composition of these residues could enable their valorization as a low-cost and sustainable resource for nutraceutical applications. In this context, a quantitative ¹H NMR-based metabolite profiling approach, complemented by HPLC-DAD and LC-MS, was employed to comprehensively characterize saffron biowaste. A total of 40 metabolites were identified and quantified by NMR, including amino acids (611.1 ± 36.5 mg/100 g FW), carbohydrates (2801.4 ± 33.7 mg/100 g FW), lipids (702.7 ± 28.2 mg/100 g FW), and saffron-specific compounds such as crocin (596.6 ± 21.5 mg/100 g FW), picrocrocin (1126.3 ± 18.9 mg/100 g FW), safranal (398.4 ± 14.8 mg/100 g FW), and crocetin (13.4 ± 0.4 mg/100 g FW). Targeted fractionation further allowed the identification of kaempferol 3-O-sophoroside (15.44 ± 0.61% w/w in dry ethanolic extract) and 3-hydroxy-γ-butyrolactone. Overall, the results highlight the rich metabolite composition of saffron production waste and support its potential reuse as a valuable source of functional ingredients within a circular economy framework. Full article

This study investigates the phytochemical profile, antioxidant capacity, and antimicrobial potential of Crocus sativus L. (saffron) tepal extracts obtained via different solvent systems. Here, a biochemical screening was performed using spectrophotometry and HPLC-DAD, while molecular docking simulations were carried out to evaluate the possible interactions between saffron tepal metabolites and bacterial target proteins. In parallel, antioxidant activity was assessed using radical scavenging assays, whereas antimicrobial potential (i.e., MIC, MBC, and MFC) was tested against selected bacterial strains. Results indicated that aqueous successive and crude extracts yielded the highest concentrations of polyphenols, flavonoids, and condensed tannins. In detail, HPLC-DAD analysis specifically identified significant levels of gallic acid, epicatechin, and various anthocyanins. These extracts demonstrated robust antioxidant and antimicrobial activities. This latter evidence was corroborated by the docking analyses, which revealed that chlorogenic acid and petunidin-3-glucoside exhibited high binding affinities for 2NRK and 2NZF, whereas epicatechin and pelargonidin effectively targeted 8ACR. These findings underscore the therapeutic potential of C. sativus tepals as natural bioactive agents, suggesting a promising role in overcoming antibiotic resistance and supporting their development for pharmaceutical applications. Full article

Background: Population aging increases susceptibility to cognitive decline, anxiety, and metabolic dysregulation, yet safe and effective interventions remain limited. Saffron (Crocus sativus L.) has been traditionally used to enhance mood and cognition, and its main metabolites, crocins and safranal, exert neuroprotective, anxiolytic, and metabolic effects. However, variability in extract composition and frequent adulteration hinder reproducibility. Objectives: To clarify the efficacy of genuine saffron preparations in aging, we investigated a saffron extract standardized for safranal and crocin content (SSE). Methods: Safranal bioavailability was first characterized in rats, followed by an evaluation of behavioral, neuroendocrine, and metabolic outcomes after 35 days of oral SSE administration (25 or 200 mg/kg/day) in 25-month-old male C57BL/6 mice. Behavioral performance was assessed using open field and novel object recognition tests, while molecular analyses targeted neuropeptides in the hypothalamus and amygdala, hippocampal plasticity markers, cortical inflammatory proteins, and hepatic lipid metabolism genes. Results: SSE administration induced a rapid but transient increase in the plasma’s safranal, confirming its bioavailability. In aged mice, the low dose prevented age-related weight loss and modulated hepatic lipid metabolism, whereas the high dose reduced anxiety-like behavior and improved recognition memory. The anxiolytic effects are consistent with elevated hypothalamic Npy, an anxiolytic peptide, reduced amygdalar Crh, a key mediator of stress and anxiety, and decreased hypothalamic Hcrt, an arousal modulator. The improvement in memory is associated with modulation of the cortical and hippocampal inflammatory and endocannabinoid proteins involved in neural plasticity. Conclusions: These findings highlight content-standardized saffron extracts as a promising multi-target nutraceuticals for healthy aging. Full article

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. Full article

Background/Objectives: Astrocytic redox-inflammatory signaling has been implicated in Parkinson’s disease (PD) pathology and may constrain hippocampal neurogenesis. We previously identified an astrocytic NOX4–MPO–OPN axis associated with impaired neurogenic capacity. Here, we tested whether a saffron-derived antioxidant (SDA; Crocus sativus extract) and Passiflora incarnata L. extract (PI) modulate this pathway in an MPTP-induced PD mouse model. Methods: Male C57BL/6J mice were randomized to Sham, MPTP, and treatment groups (n = 9/group for behavior; n = 4–5/group for histology/immunoblotting). SDA or PI (50 mg/kg/day, oral, 5 weeks) was administered, with resveratrol as a positive control. Behavioral, histological, and molecular analyses were performed by investigators blinded to group allocation where feasible. Results: SDA and PI were associated with reduced NOX4/MPO/OPN signals, mainly in GFAP-positive astrocytes, along with recovery of neurogenesis markers (Ki67, DCX, BrdU/NeuN) and synaptic markers (PSD95, synaptophysin), and improved motor performance. Mitochondrial and oxidative injury markers (TIM23, TOM20, OXPHOS subunits; 4-HNE) and apoptotic markers (Bax, cleaved caspase-3, Bcl-2) also shifted toward Sham levels. Given previous reports of Passiflora extracts’ sedative effects, we note that metabolic measures (body weight, food intake, and water intake) were similar across groups; however, specific tests for sedation or arousal were not conducted. Conclusions: These findings offer preclinical evidence that SDA and PI modulate redox-inflammatory and mitochondrial stress signatures and are associated with neurogenic, synaptic, and behavioral improvements in an acute MPTP model. Further validation in chronic/genetic PD models and pharmacokinetic/brain exposure studies will be necessary to confirm their translational potential. Full article

Saffron (Crocus sativus L.) is one of the most valued spices worldwide, rich in bioactive apocarotenoids such as crocins, picrocrocin, and safranal, which display antioxidant, neuroprotective, and anticancer properties. Saffron’s chemical composition is critical for its therapeutic efficacy and a combination of components appears essential to reach the best protection and increase tissue resilience, so stigmas were subjected to hydroalcoholic extraction followed by purification via solid-phase extraction to enriched crocin and picrocrocin fractions. The extracts were included in liposomes to enhance their bioavailability and gastrointestinal absorption by oral administration while protecting them in the harsh gastric environment, increasing their permeation and sustaining their release in the gastrointestinal tract. Liposomes were prepared by the reverse-phase evaporation method using saturated or unsaturated lipids extracted from soy. Encapsulation efficiency was determined by HPLC monitoring of trans-4GG crocin, cis-4GG crocin, and picrocrocin. The results indicate that liposomes show greater encapsulation capacity for hydrophilic apocarotenoids such as crocins (≈90% for cis-4GG, ≈50% for trans-4GG crocin) with respect to picrocrocins (<20%). These findings support the application of liposomal carriers to improve the stability, shelf-life, and potential bioavailability of saffron’s bioactive properties for nutraceutical, pharmaceutical, and functional food applications. Full article

Medicinal and Aromatic Plant (MAP) by-products constitute a vast reservoir of bioactive metabolites with antioxidant and antimicrobial properties, offering potential for the development of high added value natural products. This study focuses on the by-product (tepals) remaining during the process of receiving the stigma of Crocus sativus L. Iridaceae (saffron), which is the commercially exploitable part of the flowers. The tepals are the main part of the flowers (>95%) and are still discarded in the fields during the collection of the stigmas in Kozani, Greece. According to numerous findings, the saffron tepals are rich in flavonoids with notable biological properties, and our aim was to investigate an alternative for their management. Within this context, dry and frozen tepals were extracted at a laboratory scale through microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), followed by adsorption resin technology (ART) for the preparation of enriched extracts. Furthermore, their HPTLC profiling, the phenolic (TPC) and flavonoid (TFC) content, and the free-radical-scavenging (DPPH) and anti-tyrosinase activity were evaluated. The frozen tepals were further extracted at a pilot scale using MAE and maceration (Mc) techniques, followed by ART treatment to remove the contained sugars. The enriched extract produced at a pilot scale using MAE and ART sequentially is characterized by a high phenolic (147.2 mg GAE/g dry extract) and flavonoid (114.8 mg QUE/g dry extract) load. These findings demonstrate that saffron tepals, traditionally considered waste, can serve as a valuable raw material for producing extracts rich in phenolic derivatives, particularly flavonoids and anthocyanins. Full article

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) are powerful techniques that have been employed to analyze foodstuffs comprehensively. These techniques offer in-depth information about the chemical composition, structure, and spatial distribution of components in a variety of food products. Quantitative NMR is widely applied for precise quantification of metabolites, authentication of food products, and monitoring of food quality. Low-field ¹H-NMR relaxometry is an important technique for investigating the most abundant components of intact foodstuffs based on relaxation times and amplitude of the NMR signals. In particular, information on water compartments, diffusion, and movement can be obtained by detecting proton signals because of H₂O in foodstuffs. Saffron adulterations with calendula, safflower, turmeric, sandalwood, and tartrazine have been analyzed using benchtop NMR, an alternative to the high-field NMR approach. The fraudulent addition of Robusta to Arabica coffee was investigated by ¹H-NMR Spectroscopy and the marker of Robusta coffee can be detected in the ¹H-NMR spectrum. MRI images can be a reliable tool for appreciating morphological differences in vegetables and fruits. In kiwifruit, the effects of water loss and the states of water were investigated using MRI. It provides informative images regarding the spin density distribution of water molecules and the relationship between water and cellular tissues. ¹H-NMR spectra of aqueous extract of kiwifruits affected by elephantiasis show a higher number of small oligosaccharides than healthy fruits do. One of the frauds that has been detected in the olive oil sector reflects the addition of hazelnut oils to olive oils. However, using the NMR methodology, it is possible to distinguish the two types of oils, since, in hazelnut oils, linolenic fatty chains and squalene are absent, which is also indicated by the ¹H-NMR spectrum. NMR has been applied to detect milk adulterations, such as bovine milk being spiked with known levels of whey, urea, synthetic urine, and synthetic milk. In particular, T2 relaxation time has been found to be significantly affected by adulteration as it increases with adulterant percentage. The ¹H spectrum of honey samples from two botanical species shows the presence of signals due to the specific markers of two botanical species. NMR generates large datasets due to the complexity of food matrices and, to deal with this, chemometrics (multivariate analysis) can be applied to monitor the changes in the constituents of foodstuffs, assess the self-life, and determine the effects of storage conditions. Multivariate analysis could help in managing and interpreting complex NMR data by reducing dimensionality and identifying patterns. NMR spectroscopy followed by multivariate analysis can be channelized for evaluating the nutritional profile of food products by quantifying vitamins, sugars, fatty acids, amino acids, and other nutrients. In this review, we summarize the importance of NMR spectroscopy in chemical profiling and quality assessment of food products employing magnetic resonance technologies and multivariate statistical analysis. Full article

Saffron, branded as Repron^®, is effective in slowing the progression of several neurodegenerative diseases. Its production, however, requires specific cultivation techniques and procedures that, together with low yields, make it expensive. To address this challenge, hydroponic cultivation has been adopted. Previous studies have shown that hydroponically cultivated saffron and Repron^® share comparable chemical compositions and neuroprotective effects under oxidative stress conditions. In this study, we evaluated the protective properties of extracts derived from Crocus sativus L. waste, compared with those of saffron derived from stigmas. Human retinal pigment epithelium (ARPE-19) cells were pre-treated with extracts of various plant waste fractions before being subjected to three stress conditions: H₂O₂-induced oxidative stress (500 μM, 3 h), lipopolysaccharide (LPS; 0.25 mg/mL, 24 h), and hyperglycemia (25 mM glucose, 96 h). Saffron Repron^® served as a positive control. The results revealed that the extract derived from C. sativus waste had superior protective effects against oxidative stress and inflammation by preserving the state of the mitochondria and tight junctions (ZO-1); conversely, the tepal extract alone was more effective under hyperglycemic conditions by also modulating acrolein levels. These results suggest that different plant fractions contain bioactive compounds with specific protective actions, which together lead to increased cell survival. Full article

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. Full article

Tepals of the Crocus sativus flower constitute the most abundant floral residue during saffron production (350 kg tepals/kg stigmas). Being a natural source of polyphenols with antioxidant properties, they can be reused to create potentially valuable products for pharmaceutical applications, generating a new income source while reducing agricultural bio-waste. In this work, composite hydrogels based on blends of pectin and gellan gum containing Crocus sativus tepal extract (CSE) have been proposed for the regeneration and healing of cutaneous wounds, exploiting the antioxidant properties of CSE. Various physico-chemical and mechanical characterizations were performed. The skin permeation of CSE was investigated using Franz cell diffusion system. The composite films were cytocompatible and able to counteract the increase in ROS, restore the production of matrix proteins, and favor wound closure. To conclude, CSE-loaded composite films represent a promising strategy to promote the body’s natural healing process. In addition, by reusing saffron tepals, not only can we develop new, sustainable treatments for skin diseases, but we can also reduce agricultural waste. Full article

Background/Objectives: The global prevalence of mental health disorders, particularly anxiety and depression, has increased significantly, with rates further elevated by the COVID-19 pandemic. Conventional pharmacological treatments, while effective, often lead to side effects that can impact patient adherence and quality of life. This has driven interest in safer, natural adjunctive therapies. Crocus sativus L. (Iridaceae) (saffron) and Scutellaria baicalensis Georgi (Lamiaceae) (scutellaria) have individually shown potential, in humans and animals, respectively, as mood regulators, with bioactive compounds that modulate neurotransmitter systems and possess anti-inflammatory and anxiolytic effects. This study aimed (1) to explore the efficacy and safety of scutellaria extracts in humans and (2) to test a possible synergistic effect when combining scutellaria and saffron on mood regulation in individuals experiencing mild-to-moderate depressive symptoms. Methods: In a randomized, double-blind, placebo-controlled trial, 180 participants with mild-to-moderate depressive symptoms were assigned to receive either scutellaria extract alone (SCUTELL’UP^®), saffron extract alone (SAFFR’ACTIV^®), a combination of scutellaria and saffron extracts (SAFFR’UP^®), or a placebo for six weeks. The primary outcome was assessed using a standardized depression scale (Beck Depression Inventory). The secondary outcomes, including anxiety, emotional state, well-being level, and sleep quality, were all assessed using validated questionnaires. Safety and tolerability were evaluated throughout the study period. Results: The results confirmed the beneficial effects of saffron extract on depressive and anxious symptoms, as well as its role in improving sleep quality. For the first time in humans, scutellaria extract demonstrated a positive effect on mood regulation. Furthermore, a synergistic effect of the combination of these two extracts was identified, leading to enhanced improvements in depressive and anxious symptoms and emotional well-being among individuals with mild-to-moderate depression, compared to the placebo group. Minimal adverse effects were reported across all treatment groups. Conclusions: This natural adjunctive nutritional strategy offers a promising alternative for individuals seeking safer options for mental health support. Further research is warranted to exclude potential long-term side effects and to explore potential mechanisms of this combined supplementation. Full article

Plant exosomes exhibit high stability and easy absorption, and have emerged as promising bioactive tools due to their potential health benefits and biomedical applications. Saffron tepals contain abundant metabolites with potential therapeutic properties and were used for exosome extraction by ultracentrifugation and gradient purification. The exosomes showed an average particle size of 151.5 ± 79.6 nm and exhibited a spherical morphology. Five well-conserved miRNAs—miR157, miR166, miR168, miR396, and miR398—were identified in the exosomes, which are involved in the coordination of growth and physiological plant responses with endogenous and environmental abiotic and biotic signals, and their potential targets in mammals are upregulated in specific cancer types and associated with inflammation. Proteome analysis revealed an enrichment of proteasome proteins, ribosomal proteins, and proteins involved in the cytoskeleton, transport across the membrane (ABC transporters), and vesicle trafficking (RAB GTPases, TM9SF and Coatomer subunits). Metabolite analyses showed mainly anthocyanins. The exosomes have selective stimulatory activity on macrophages, increasing the expression of surface molecules (CD80 and CD86), and cytokines (IL-1β, IL-6, and TNF-α), but not the levels of IL-10. Overall, these results indicated that saffron flowers are an effective and abundant source of exosomes as new nanomedicines for human health. Full article

Saffron petals represent floral biomass generally wasted due to rapid deterioration. Previous characterization studies have revealed the presence of bioactive compounds in petals, such as flavonols and anthocyanins. Petal stabilization is a challenge for the efficient isolation of these compounds. This research evaluated three different drying techniques before the solid–liquid extraction of bioactive compounds: oven-drying (40 and 60 °C), lyophilization, and vacuum evaporation (25 and 50 °C). The characterization of the extracts allowed the annotation of 22 metabolites with a quantitative predominance of anthocyanins and derivatives of kaempferol and quercetin. Oven-drying at 60 °C was the most suitable approach for extracting minor compounds, such as crocins and safranal, at concentrations below 1 mg/g dry weight. Vacuum evaporation (50 °C) and lyophilization were the most recommended strategies for efficiently isolating flavonoids. Therefore, drying saffron petals is crucial to ensure the efficient extraction of bioactive compounds. Full article