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Ethnopharmacological Relevance: Saffron is derived from the dried stigmas of Crocus sativus L., which was considered by ancient nations for food and medicinal purposes. In traditional medicine, the therapeutic use of Crocus sativus includes antispasmodic, antitussive and expectorant., Aim of the Study: Mitochondrial fusion, fission, biogenesis, and mitophagy are essential processes for maintaining mitochondrial dynamics in response to cellular stress. The primary objective of this research was to examine how crocin affected the levels of important mitochondrial regulators, including Drp1, Pgc1α, Nrf1, and Mfn2, in the lung tissue of ovalbumin-sensitized mice., Materials and Methods: A total of fifty male BALB/C mice were randomly assigned to five unique groups (n = 10 for each group), including the control group, ovalbumin-sensitized group (OVA), OVA group treated with 30 mg/kg of crocin, OVA group treated with 60 mg/kg of crocin, and OVA group treated with 1 mg/kg of dexamethasone. Post-sensitization and ovalbumin challenge, mice lung tissues were evaluated for the expression of Drp1, Pgc1α, Nrf1, and Mfn2 mRNA levels using real-time PCR as well as histopathological assessments., Results: In the OVA group, there was a significant elevated in inflammatory cells such as eosinophils, neutrophils, macrophages, and lymphocytes; however, crocin (both concentrations) and dexamethasone intervention showed significant inhibitory effects (P < 0.01 to P < 0.001). Moreover, an increase in the expression of Drp1, Pgc1α, and Nrf1 levels was seen in the OVA group, while crocin and dexamethasone showed protective benefits (P < 0.05 to P < 0.001). Furthermore, the levels of Mfn2 were reduced in the lung tissue of mice exposed to ovalbumin, but this decrease was reversed by crocin 60 (P < 0.05) and dexamethasone treatment (P < 0.001)., Conclusion: In mice with OVA sensitization, the balance of mitochondrial dynamics in lung tissue was disrupted, but intervention of crocin identified to have a protective effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Saffron is one of the traditional medicinal herbs, which contains various active ingredients, such as safranal, crocin, saffron acid, etc. It has anti-inflammatory, antioxidant, and anti-cancer properties, and is widely used in clinical practice. The anti-cancer efficacy of saffron has been previously confirmed, but its anti-cancer mechanism in colorectal cancer remains unclear., Objective: We investigated the effect of active compounds of saffron on the efficacy of immunotherapy for colorectal cancer., Methods: TCMSP and liquid chromatography-mass spectrometry analysis (LC-MS), GeneCards, and DisGeNET databases were used to identify the active compounds of saffron, drug targets and the disease targets of colorectal cancer. They were then subjected to Gene Ontology Enrichment (GO) and Signalling Pathway Enrichment (KEGG) analyses. The core targets and corresponding compounds were selected for molecular docking. The effect of active components of saffron on the proliferation of CT26 and HCT116 cells was investigated using the cell counting kit-8 (CCK-8). In vitro experiments were conducted by subcutaneous injection of CT26 cells to establish a colon cancer model. Enzyme-linked immunosorbent assay (ELISA), western blotting (WB), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and flow cytometry (FCM) were employed to validate the effects of saffron on colorectal cancer immunotherapy., Results: 1. LC-MS analysis revealed that the main active component of saffron extract was crocin. The active chemicals of saffron intersected with 170 colorectal cancer targets, with 17 predicting targets for saffron treatment. GO and KEGG enrichment analyses revealed that the active components of saffron can prevent colorectal cancer development by enhancing Th17 cell differentiation and the IL-17 signaling pathway. 2. In vitro studies revealed that saffron alcohol extract, crocin, and safranal can suppress the proliferation of CT26 and HCT116 cells. 3. In vivo studies showed that crocin and safranal can increase the body mass and decrease the tumor mass of loaded mice, decrease the serum level of IL-17, and lower the mRNA expression level of IL-17, IL-6, TNF-α, TGF-β, and PD-L1 and IL-17, PD-L1 protein in tumors. This inhibitory effect was strengthened after combined immunotherapy. In addition, saffron modulated CD4 + and CD8 + T cells and the CD4 + /CD8 + T ratio in mouse spleens., Conclusion: The active components of saffron can reduce the expression of inflammatory factors and ameliorate the immunological microenvironment of tumors via the IL-17 signaling pathway, thereby improving the efficacy of immunotherapy for colorectal cancer. This study provides pharmacological support for the application of saffron in enhancing the efficacy of immunotherapy for colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Saffron petals are usually considered as waste after saffron harvest. However, saffron petals contain many important phytochemical components (e.g. quercetin and kaempferol), which may alleviate oxidative damage in human cells., Results: The contents of flavonoids and crocin in different parts of saffron were analyzed. The protective effects of flavonoids from saffron on oxidative damage of B16 cells were investigated. Saffron stigma contained high contents of crocin and picrocrocin, whereas flavonoid content (quercetin, 4.03 ± 0.33 mg g -1 DW; kaempferol, 47.80 ± 0.60 mg g -1 DW) was higher in saffron petals than in other parts. Incubation of B16 cells with quercetin (10-30 μmol L -1 ) and kaempferol (20-30 μmol L -1 ) obtained from saffron extracts could significantly increase the total antioxidant capacity (T-AOC) and the activity of NADPH:dehydrogenase quinone-1 (NQO1) to alleviate H 2 O 2 -induced oxidative damage. Quercetin was better than kaempferol in increasing NQO1 activity and T-AOC. Quercetin extracted from saffron petals could induce NQO1 expression through regulating kelch-like ECH-associated protein-1/nuclear factor erythroid 2-related factor-2 signaling pathway to protect B16 cells from oxidative damage., Conclusion: The content of kaempferol-3-O-sophoroside and quercetin-3-O-sophoroside was higher in saffron petals than in other parts of saffron. The kaempferol and quercetin obtained from saffron petals could enhance the activity of antioxidant enzyme NQO1 and T-AOC in B16 cells. This indicated that saffron petals, as a potential functional food, may prevent diseases caused by oxidative stress. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Ethnopharmacological Relevance: The herbicide paraquat (PQ) is highly toxic, capable of inducing severe lung inflammation and oxidative stress, resulting in lung fibrosis and respiratory failure. Previous research has demonstrated a range of pharmacological effects associated with Crocus sativus. L (Cs) through its anti-inflammatory, antioxidant and immunomodulatory properties. Pharmacological studies support the widespread use of Cs in traditional medicine to treat respiratory disorders such as coughs and asthma., Aim of Study: This study aimed to investigate the preventive impact of Cs extract and pioglitazone (Pio) on lung inflammation, oxidative stress, pathological alterations, and tracheal reactivity induced by inhaled PQ in rats as compared to dexamethasone (Dexa)., Methods: The control (Ctrl) group of rats was administered with saline aerosol, while the remaining six groups received PQ aerosol eight times every other day. The six PQ exposure groups were treated daily during the exposure period to PQ with either; saline alone, low dose Cs, High dose Cs, Pio alone, Pio combined with low dose Cs, or Dexa of 16 days., Results: In the PQ group, the levels of superoxide dismutase (SOD), catalase (CAT), and thiol in the bronchoalveolar lavage fluid (BALF) were declined whereas, the levels of MDA, total and differential WBC, and lung tissue levels of tumor necrosis factor (TNF-α) and Interleukin 10 (IL-10), tracheal responsiveness (TR) to methacholine and lung pathological changes were enhanced. The measured variables showed significant improvement in all treated groups, except for a few variables in Cs (L). The combined Cs (L) + Pio showed higher effects than Cs (L) and Pio alone. For all comparisons, p values were <0.05 to <0.001., Conclusions: The results showed preventive effect of Cs comparable to that of Dexa and the potential additive preventive capabilities of the Cs and Pio indicate that the involvement of the PPARγ receptor is implicated in the effects induced by Cs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Saffron extract (SE) was electrospun into pullulan-pectin (Pl-Pc), pullulan-pea protein-pectin (Pl-Pp-Pc), or zein nanofibers (NFs) for transdermal food supplement. The in vitro transdermal permeation mechanism and kinetics of SE from NFs were studied and compared with those of in vitro digestion. The ATR-FTIR spectra of NFs provided information on the interactions between SE and wall biopolymers. The release of SE from NFs was investigated in stimulated gastrointestinal media (SGF and SIF) using a dialysis bag, and transdermal permeation studies were performed via a membrane in a Franz diffusion cell. The wettability and swelling ratio of the NFs were determined. The Pl-Pc-SE sample, which has the lowest contact angle and the highest swelling index, resulted in the highest release of SE during digestion. The Ritger-Peppas and Higuchi models best represented the experimental release data from digestion and transdermal permeation. The release profile of SE from zein NFs in SGF was described using a non-Fickian mechanism. In contrast, the release mechanism for Pl-based NFs in SGF and all NFs during both release experiments was Fickian-controlled diffusion transport. The results indicate that NFs can be successfully used for the controlled delivery of SE and have the potential for transdermal applications as a dietary supplement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Saffron has been utilized in numerous studies as an additive to augment egg quality and to enhance the oxidative stability of egg yolk.However, there is limited knowledge on the responses of hens to dietary supplementation with saffron petals on egg chemical composition, fecal mineral excretion, and ammonia emission., Objectives: The objective of this study was to investigate the influence of saffron petal extract-enriched diet on egg quality, blood metabolites and odorous gas emission from excreta in laying hens., Methods: The experimental methodology involved a feeding trial conducted over a period of 12 weeks, using 200 Hy-line W36 laying hens aged 39 weeks. The dietary intervention included a basic diet (serving as a control with no supplementation), as well as diets fortified with 40, 60 or 80 parts per million (ppm) of hydroalcoholic saffron petal extract in a completely randomized design., Results: Results showed that the inclusion of saffron petal extract in the diet did not significantly affect the egg crude protein, fat and ash content. However, a significant reduction (p < 0.05) in yolk cholesterol concentration was observed. No substantial effect was noted on feed intake, feed conversion ratio (FCR) and egg weight (p > 0.05). On the other hand, a significant increase (p < 0.05) was documented in the egg production percentage of hens fed on the 80 ppm saffron petal extract diet compared to the control. Furthermore, saffron petal extract supplementation resulted in a significantly lower yolk cholesterol together with reduced serum cholesterol content (p < 0.05). Blood glucose and triglyceride concentrations also demonstrated a decrease subsequent to the inclusion of 80 ppm saffron petal extract. The excretion of faecal minerals did not show any significant alterations due to the dietary interventions (p > 0.05). Notably, hens supplemented with 60 and 80 ppm saffron petal extract displayed significantly diminished concentrations of faecal ammonia (NH 3 ) emissions (p < 0.05) compared to the control., Conclusion: The study suggests that the inclusion of 80 ppm saffron petal extract in the diet of laying hens may serve as a functional food source to mitigate cholesterol levels in egg yolk and blood serum, as well as to reduce faecal ammonia emissions., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Contamination is not surprising in light of the ubiquitous nature of the fungi that produce aflatoxin and ochratoxin A. The presence of these toxins in the broiler diet leads to increased losses, an increased feed conversion ratio, and decreased productivity., Objectives: This study aimed to investigate the effects of the use of hydroalcoholic extracts of saffron petals, yeast cell walls and bentonite in the diets of broiler chickens contaminated with aflatoxin B 1 and ochratoxin A., Methods: In a completely randomised design, 350 one-day-old Ross 308 broilers were allocated into seven treatment groups and five replications: a negative control diet (without toxins or additives), a positive control diet (2.5 mg/kg aflatoxin + 2 mg/kg ochratoxin A (mg/kg) and diets containing toxins with a commercial toxin binder or yeast cell wall, processed bentonite or saffron petal extract alone or together., Results: Compared with those in the positive control treatment, the relative weights of the carcasses, breasts and drumsticks improved with the addition of toxic adsorbent compounds (p < 0.05). Compared with the control treatment, the inclusion of a toxin binder had a significant effect on the concentration of glucose (p < 0.05). The concentrations of alanine aminotransferase and gamma-glutamyltransferase enzymes in the yeast cell wall + processed bentonite + saffron petal extract treatment were lower than those in the other treatments (p < 0.05). Toxin adsorbent compounds significantly improved the morphology of the small intestine in chickens fed contaminated diets (p < 0.05)., Conclusion: The inclusion of toxic adsorbent compounds can reduce the negative effects caused by the presence of Aflatoxin B 1 and Ocratoxin A. Saffron petal extract can potentially be used to modulate diets contaminated with Aflatoxin B 1 and Ocratoxin A, which is best achieved with 750 mg/kg saffron petal extract along with 0.1% yeast cell wall extract and 1% processed bentonite., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

This work represents the first successful application of a molecularly imprinted polymer (MIP)-based electrochemical sensor for the sensitive and selective determination of the first developed proteasome inhibitor, bortezomib (BOR). BOR is used for the treatment of multiple myeloma, gastrointestinal stromal tumors, and mantle cell lymphoma. It shows its desired effect through the boronate group and can be administered intravenously or subcutaneously. The MIP-based electrochemical sensor design includes the integration of green-synthesized saffron-based copper nanoflowers (CuNFs) from Crocus sativus L. to increase the active surface area and porosity of the glassy carbon electrode (GCE) surface. 2-Acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was selected as the functional monomer along with other MIP components. Detailed characterizations of the developed CuNFs/AMPS/MIP-GCE sensor and CuNFs were performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDX), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The indirect measurement approach using 5.0 mM [Fe(CN) 6 ] 3-/4- solution was used to determine BOR in the linear range of 2.5 × 10 -13  M - 2.5 × 10 -12  M (0.25-2.5 pM). The LOD and LOQ values of the sensor obtained at the fM level (29 fM and 96.7 fM), which has a linear response in the commercial human serum sample in the same concentration range, emphasize its sensitivity (1.89 × 10 13 and 2.14 × 10 13  μA/M for standard solution and serum). The repeatability and reproducibility of the sensor were between 0.87 % and 2.17 %, showing its reliability. The successful performance of the sensor in the presence of metabolites belonging to BOR demonstrates its unique selectivity. The selectivity was demonstrated via relative imprinting factor (IF') values (higher than 3.5) against BOR's metabolites. The stability of the CuNFs/AMPS/MIP-GCE sensor was found to be 5 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects., Purpose: The present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered., Methods: Studies were identified through a systematic and comprehensive search in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within the comprehensive studies in the review., Results: Saffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-κB, IL-1β, IL-6, TNF-α, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations., Conclusion: Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Despite the unique properties of graphene oxide (GO) as a green adsorbent, its low structural stability presents a drawback. This study aimed to modify the properties of GO through its functionalization with chitosan (CH), cross-linked with glutaraldehyde (GLU), and synthesized via the freeze-drying method (GO-CH/GLU). Microscopic analysis illustrated that covering the GO sheets with CH and nanoparticles (NPs) resulted in a 15.8 % increase in d-spacing and a 600 % increase in sheet thickness. The GO-CH/GLU composite was utilized for the separation/purification of crocin from saffron extract under varying pH (5-9), temperature (298-318 K), stirring rate (100-300 rpm), and crocin concentration (25-200 mg/mL). The Freundlich isotherm and pseudo-second-order kinetic models provided a good fit for crocin adsorption. Thermodynamic analysis revealed that the process was endothermic, spontaneous, and physical. Optimal adsorption conditions in batch mode were pH 7, a stirring rate of 300 rpm, a temperature of 318 K, and a crocin concentration of 100 mg/mL. These conditions were applied in a continuous system, resulting in a crocin separation efficiency of 94.17 % at 180 mL/h. Additionally, HPLC data indicated that the purity of separated crocin exceeded 90 %. So, the GO-CH/GLU composite is a promising and economical adsorbent for the food industry., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the present contribution, a novel non-targeted volatilomic study based on headspace GC-IMS (HS-GC-IMS) was developed for the authentication and geographical origin discrimination of saffron. In this regard, multivariate curve resolution-alternating least squares (MCR-ALS) was employed to recover the pure GC elution and IMS profiles of saffron metabolites. Iranian saffron samples from seven important areas were analyzed by HS-GC-IMS. The resulting second-order GC-IMS datasets were organized in a augmented matrix and processed using MCR-ALS with various constraints. The MCR-ALS resolved GC profiles were analyzed by different pattern recognition techniques; principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and data driven-soft independent modeling of class analogy (DD-SIMCA). The saffron samples were assigned to their seven geographical origins with an accuracy of 89.0 %. Additionally, four adulterants (style, safflower, madder and calendula) were reliably detected with over 94.0 % accuracy. In this context, GC-IMS substantially outperformed the commonly used FT-NIR spectroscopy approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study explores the binding properties of two important constituents from Crocus sativus L (crocin and crocetin) with myosin, examining their influence on antioxidant capacity in myosin and a grilled meat model. And their impact on cytoprotective potential of myosin digestion products was also assessed in Caco-2 cells. Crocin and crocetin exhibited discernible binding affinity to myosin via static quenching, which induced conformational alterations that bolstered the antioxidant capacity of myosin, preventing peroxidation, which also corroborated in a grilled meat model. Crocin resulted in greater enhancement of antioxidant capacity and binding affinity, as confirmed by quantum chemical calculations. Molecular dynamics simulations revealed the stable binding of crocin to GLU:272, GLU:606, GLN:628, and PHE:417 residues of myosin. In addition, crocin substantially enhanced the protective efficacy of myosin digestion products against H 2 O 2 -induced damage in Caco-2 cells by upregulating superoxide dismutase and GSH-Px and simultaneously downregulating reactive oxygen species and malondialdehyde levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The saffron composition is being widely studied for authenticity and traceability, but very few works have been carried out to investigate the relationship between the chemical and physico-chemical properties of saffron solutes and their technological functionality in colloidal systems. This study aims at evaluating the surface properties of saffron extracts obtained using solvents of different polarities to achieve extracts with different compositions in terms of the pattern and content of polar and medium polarity crocins. The air-water surface was evaluated alone and in the presence of Tween 20 at different surfactant-extract ratios. Saffron extracts were able to decrease the surface tension of the aqueous phase, indicating the presence of surface-active compounds. In the mixed saffron extract-Tween 20 systems, competitive adsorption at the air-water interface occurred when the surfactant was present at a low concentration, while at concentrations higher than the CMC, Tween 20 hindered the adsorption of the extract surface-active compounds. The results highlight the interesting technological functionality of saffron extracts for applications in colloidal systems. To better exploit their use in the design and development of formulated foods, nutraceutics and pharma products, further studies are needed to unravel the relationship between the composition of saffron extracts and corresponding surface activity.

Crocus sativus L. is a perennial crop for its valuable active compounds. Plant-associated microbes impact on the quality and efficacy of medicinal herbs by promoting bioactive components accumulation. However, how microbes influence the accumulation of bioactive components in saffron have not been well studied. Here, the microbiome in C. sativus derived from 3 core production areas were deciphered by 16S rDNA sequencing and the relationship between endophytes and bioactive ingredients were further investigated. The main results are as follows: (1) Both Comamonadaceae and Burkholderiaceae were positively correlated with the content of bioactive components in the stigmas. (2) The synthesis of crocin was positively correlated with Xanthomonadaceae, negatively correlated with Lachnospiraceae and Prevotellaceae. Therefore, further investigation is required to determine whether Xanthomonadaceae plays an unknown function in the synthesis of crocin. These findings provide guidelines for disentangling the function of endophytes in the production of bioactive ingredients and thus for microbe-mediated breeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Saffron (Crocus sativus L.) is a plant known for its diverse medicinal and nutritional properties, which has adapted well to arid and semi-arid regions of the world, particularly in the Middle East. Research on saffron wastes (SW) as a dietary additive for small ruminants is limited. Therefore, two primary experiments were designed to evaluate the nutritional potential of SW. In the first trial, the nutritional value of SW collected from various regions in northeast Iran was assessed through proximate analysis and in vitro procedures. In the second trial, the effects of incorporating SW (a 1: 1 mixture from all regions, w: w) at two levels (30 and 60 g/day) into the diets of Afshari male lambs were investigated in comparison to a control diet. Except for dry matter and ether extract contents, other chemical and mineral compounds varied among the SW collected from different regions. The samples displayed diversity in potential gas production and estimated dry matter intake (DMI). In the in vivo experiment, DMI, nutrient digestibility, and most blood metabolites were not significantly affected by the addition of SW; however, malondialdehyde, total antioxidant capacity, and cholesterol levels were respectively decreased, increased, and decreased in lambs fed 60 g SW/day compared to the control group. Overall, SW collected from various regions demonstrated different nutritional values. Although the dietary inclusion of SW at the level of 60 g/day did not adversely effect on DMI, nutrient digestibility, or certain blood metabolites, it is suggested for its potential improvement in lambs' health indicators. Long-term studies are recommended for future SW evaluation in vivo., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

So far, compliance with ISO 3632 standard specifications for top-quality saffron guarantees good agricultural and post-harvest production practices. Tracking early-stage oxidation remains challenging. Our study aims to address this issue by exploring the visible, fluorescence, and near-infrared spectra of category I saffron. Using a multi-spectral sensor, we tested fresh and artificially aged saffron in powder form. High autofluorescence intensities at 600-700 nm allowed calibration for the 'content of aged saffron'. Samples with minimum coloring strength (200-220 units) were classified as 70% aged, while those exceeding maximum aroma strength (50 units) as 100% aged. Consistent patterns across origin, age, and processing history indicated potential for objectively assessing early-oxidation markers. Further analyses uncovered multiple contributing fluorophores, including cis-apocarotenoids, correlated with FTIR-based aging markers. Our findings underscore that sensing autofluorescence of traded saffron presents an innovative quality diagnostic approach, paving new research pathways for assessing the remaining shelf-life along its supply chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Crocus sativus L. is a both medicinal and food bulbous flower whose qualities are geographically characterized. However, identification involving different places of origin of such substances is currently limited to single-omics mediated content analysis. Integrated metabolomics and proteomics, 840 saffron samples from six countries (Spain, Greece, Iran, China, Japan, and India) were analyzed using the QuEChERS extraction method. A total of 77 differential metabolites and 14 differential proteins were identified. The limits of detection of the method were 1.33 to 8.33 μg kg -1 , and the recoveries were 85.56% to 105.18%. Using homology modeling and molecular docking, the Gln84, Lys195, Val182 and Pro184 sites of Crocetin glucosyltransferase 2 were found to be the targets of crocetin binding. By multivariate statistical analysis (PCA and PLS-DA), different saffron samples were clearly distinguished. The results provided the basis for the selection and identification of high quality saffron from different producing areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflicting financial interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The global demand for fish and fish products has increased due to population growth and healthier food choices. However, bacterial infections caused by Aeromonas species pose a challenge. Antibiotics are crucial for disease control, but multidrug resistance is a global concern. Eco-friendly disease management methods, like saffron, have been identified as potential treatments., Aim: The study investigated the effects of dietary supplementation with Saffron on Nile tilapia's growth performance, immune response, and disease resistance., Methods: 180 fish were acclimatized for 2 weeks and randomly allocated into three groups. The first group served as a control, while the other two groups were fed a basal diet supplemented with Saffron at 1.5 g/kg (T1) and 0.5 g/kg (T2), respectively, for 12 weeks. Biochemical blood parameters. Histopathology and immunohistochemical studies were performed on the gills, liver, and spleen tissues., Results: Following the feeding trial with Saffron supplement, especially at higher levels enhanced weight gain, Growth performance, plasma total protein, and globulin showed higher levels in fish groups with dietary with Saffron at 1.5 g/kg (T1) and 0.5 g/kg (T2) than in fish fed the control diet Regulate the immune response in lysozyme activity and immunoglobulin M (IgM). Regeneration of gills, liver, and spleen tissues was noticed Furthermore, saffron-treated organs exhibited immunoreactivity to TNF-α was mostly seen in the liver and gills, although it was also somewhat in the kidney and spleen and CD68, the group were challenged with Aeromonas hydrophila , improved its defenses against A. hydrophila , immunity, and disease resistance than the control group., Conclusion: The results showed that saffron supplementation significantly increased the survival rate of fish challenged with A. hydrophila . It also enhanced the immune response of fish, as evidenced by increased levels of serum immunoglobulins and lysozyme activity. These findings suggest that saffron supplementation could be a promising strategy for the prevention and treatment of bacterial infections in aquaculture., Competing Interests: The authors declare that there is no conflict of interest.

During ageing, the brain is vulnerable to a growing imbalance of the antioxidant defence system, resulting in increased oxidative stress. This condition may be mainly responsible for cognitive decline, resulting in synaptic transmission disruptions and the onset of neuronal dysfunction. In this context, developing efficient preventive and therapeutic strategies against increased oxidative stress and decreased antioxidant defence mechanisms should be considered a public health priority to promote healthy ageing. Therefore, the current study explored the benefits of a novel combination of green tea, saffron, trans-Reveratrol, and citicoline, called MIX, on improving intracellular processes to ameliorate the mechanisms linked to cognitive decline under oxidative stress conditions. First, the ability of MIX to cross the blood-brain barrier (BBB) was evaluated in an in vitro model, analysing TEER value and the specific tight junctions; second, the CCF-STTG1 cell line was pretreated with 200  µ M H 2 O 2 for 30 min to explore the effects of the single active compounds and their combination under oxidative stress conditions. Our results demonstrated for the first time the synergistic effects of the new combination to improve the absorption rate of individual agents through the BBB and maintain its integrity. Subsequently, further research was done to assess the positive role of the combination to counteract oxidative damage; as expected, MIX restored the neurodegenerative state activated by 200  µ M H 2 O 2 , reducing mitochondrial damage, and improving survival pathways. Additionally, MIX acted as a regulator of both cellular energy metabolism and apoptosis, reducing the inflammatory state activated by oxidative stress. Finally, MIX can balance neurotrophin production to prevent mitochondrial disruption. In conclusion, MIX counteracted the adverse effects of brain oxidative stress, suggesting that this new proposed formulation prevents the molecular mechanisms underlying the onset of cognitive decline, even in support of conventional therapy., Competing Interests: The authors declare that they have no competing interests. Francesca Uberti is a cofounder of noiVita Srls. Dr. Stefania Battaglia and Dr. Valeria Curti are employees of Kolinpharma S.p.A., a nutraceutical company that produces and commercialises food supplements. These authors report no involvement of the company in the research that could have influenced the outcome of this work., (Copyright © 2024 Simone Mulè et al.)

Palladium (Pd) and zinc oxide (ZnO) (Pd/ZnO NPs) bimettalic nanocomposites still lag much too far behind other nanoparticles investigated for various biological uses in the area of cancer treatments. Chemically created nanoparticles agglomerate under physiological conditions, impeding their use in biomedical applications. In this study, a straightforward and environmentally friendly method for creating bimetallic nanoparticles (NPs) by combining palladium (Pd) and zinc oxide (ZnO) using Crocus sativus extract (CS-Pd/ZnO NCs) was reported; the bio-synthesize bimetallic palladium/zinc oxide nanocomposites and their antioxidant and anti-cancer properties were assessed. The developed Pd/ZnO NPs were characterized using different approaches, including UV-vis, DLS, FTIR, EDX, and SEM analyses. The present investigation shows how nanocomposites are made, their distinctive properties, antioxidant activity, anticancer mechanisms, and their potential therapeutic applications. DPPH and ABTS tests were used to investigate antioxidant activity. Further, the effects of CS-Pd/ZnO NCs on HeLa cells were assessed using the cell viability, ROS generation, MMP levels, and induced apoptosis. Apoptosis induction was measured using an Annexin V-fluorescein isothicyanate assay. Cell DNA was stained with propidium iodide to evaluate the impact upon this cell cycle. Time-dependent cell death was carried on by CS-Pd/ZnO NCs. The maximum inhibitory effect was 59 ± 3.2 when dosages of 4.5 µg/mL or higher were delivered after 24 h of treatment. Additionally, the CS-Pd/ZnO NCs caused HeLa cells to undergo apoptosis. Apoptotic HeLa cells were present in 35.64% of the treated cells at 4.5 µg/mL, and the cell cycle arrest at G0/G1 phase occurred concurrently. According to these findings, the CS-Pd/ZnO NCs may be a promising candidate for the creation of brand-new cervical cancer treatment., Competing Interests: Declarations Ethical Approval Not applicable. Consent to Participate Not applicable. Consent for Publication All authors agreed to publish this paper in this journal. Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Crocin, a natural bioactive compound derived from saffron (Crocus sativus) and other Crocus genera, has gained significant attention recently due to its potential therapeutic properties. The multifaceted nature of crocin's biological effects has piqued the interest of researchers and health enthusiasts, prompting further investigations into its mechanisms of action and therapeutic applications. This review article comprehensively explores the emerging evidence supporting crocin's role as a promising ally in protecting against metabolic disorders. The review covers the molecular mechanisms underlying crocin's beneficial effects and highlights its potential applications in preventing and treating diverse pathological conditions. Understanding the mechanisms through which crocin exerts its protective effects could advance scientific knowledge and offer potential avenues for developing novel therapeutic interventions. As we uncover the potential of crocin as a valuable ally in the fight against disorders, it becomes evident that nature's palette holds remarkable solutions for enhancing our health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The preventive effect of saffron against Alzheimer's disease (AD) has been reported. Herein, we studied the effect of Cro and Crt, saffron carotenoids, on the cellular model of AD. The MTT assay, flow cytometry, and elevated p-JNK, p-Bcl-2, and c-PARP indicated the AβOs-induced apoptosis in differentiated PC12 cells. Then, the protective effects of Cro/Crt on dPC12 cells against AβOs were investigated in preventive and therapeutic modalities. Starvation was used as a positive control. RT-PCR and Western blot results revealed the reduced eIF2α phosphorylation and increased spliced-XBP1, Beclin1, LC3II, and p62, which indicate the AβOs-induced autophagic flux defect, autophagosome accumulation, and apoptosis. Cro and Crt inhibited the JNK-Bcl-2-Beclin1 pathway. They altered Beclin1 and LC3II and decreased p62 expressions, leading cells to survival. Cro and Crt altered the autophagic flux by different mechanisms. So, Cro increased the rate of autophagosome degradation more than Crt, while Crt increased the rate of autophagosome formation more than Cro. The application of 4μ8C and chloroquine as the inhibitors of XBP1 and autophagy, respectively, confirmed these results. So, augmentation of the survival branches of UPR and autophagy is involved and may serve as an effective strategy to prevent the progression of AβOs toxicity., (© 2023 John Wiley & Sons Ltd.)

Depression is a significant mental health challenge globally. While traditional antidepressants are effective, they often have unwanted side effects. Saffron, a natural spice derived from Crocus sativus L., has emerged as a potential alternative therapy for depression. Researchers have found that its components such as crocin, crocetin, and safranal have been found to mitigate depressive symptoms through neurotransmitter regulation, anti-inflammatory effects, and neuroprotection. Clinical trials suggest that the effectiveness of saffron in treating mild to moderate depression is comparable to that of standard medications, and animal studies support these results, showing behavioral improvements with saffron treatment. Saffron is particularly appealing due to its safety and lower incidence of side effects, making it suitable for those sensitive to conventional drugs. Additionally, its antioxidant properties may offer further health benefits. However, challenges such as determining the appropriate dosage, prohibitive cost, and the limited availability of quality saffron need to be addressed. Most research on saffron's efficacy is short-term; thus, long-term studies are essential to understand its full therapeutic potential and ongoing antidepressant effects. While saffron is safe in terms of its culinary value, higher therapeutic doses require careful monitoring for drug interactions and side effects. In summary, saffron represents a promising direction in depression treatment, with benefits potentially matching those of standard treatments and a better safety profile. However, further research is necessary to establish clear guidelines for its use, optimize dosing, and assess long-term outcomes. Saffron offers a natural treatment path for depression, but its use must be controlled and supported by scientific evidence., (Copyright ©2024, Yale Journal of Biology and Medicine.)

The main constituents of saffron are the apocarotenoids crocins and crocetin, present in the stigmas. Numerous healthy properties, especially those related to the effects on the central nervous system, have been attributed to these compounds but the metabolites responsible for these effects are still unknown. Previous evidences in animal models suggest a role for the gut microbiota in the pharmacokinetics and the neuroprotective effects of these compounds. However, the interaction between these apocarotenoids and the gut microbiota has been poorly studied. In this article, we have thoroughly investigated the batch fermentation of crocin-1 and crocetin (10 μM) with human fecal samples of two donors at different incubation times (0-240 h) using a metabolomic approach. We corroborated a rapid transformation of crocin-1 which looses the glucose molecules through de-glycosylation reactions until its complete transformation into crocetin in 6 hours. A group of intermediate crocins with different degrees of glycosylation were detected in a very short time. Crocetin was further metabolized and new microbial metabolites produced by double-bond reduction and demethylation reactions were identified for the first time: dihydro and tetrahydro crocetins and di-demethyl crocetin. In addition, we detected changes in the levels of the short chain fatty acids valeric acid and hexanoic acid suggesting further structural modifications of crocetin or changes in the catabolic production of these compounds. This research is a pioneering study of the action of the human gut microbiota on the saffron apocarotenoids and goes one step further towards the discovery of metabolites potentially involved in the benefits of saffron.

Background: Quality properties of 14 saffron samples from Iran, Spain, and Türkiye were compared., Results: Significant differences were observed between anthocyanins, volatile compounds, fatty acids, total phenolic content, and antioxidant activity of saffron samples (P < 0.05). Besides, significant differences in color parameters were observed. Moreover, a total of 13 volatile compounds were identified in the saffron samples using. headspace-solid-phase microextraction-gas chromatography-mass spectrometry, safranal and α-isophorone being the two predominant aroma compounds. Regarding fatty acids, significant differences were seen in the fatty acid profiles of saffron samples (P < 0.05), while linoleic acid was the most concentrated fatty acid. In terms of sensory properties, different concentrations of safranal, α-isophorone and 4-ketoisophorone may lead to significant differences in the odor and taste attributes of saffron samples (P < 0.05)., Conclusion: Changes in corm origin along with climate and agricultural conditions may affect the quality characteristics of saffron cultivated in different geographical areas to a significant degree. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Depression is one of the most common psychiatric conditions worldwide, with an annual escalation in prevalence. The serotonin (5-Hydroxytryptamine [5-HT]) metabolism through the gut-brain axis has been revealed to be related to the development of depression. Our previous study demonstrated that Lactococcus lactis WHH2078 alleviated depression in mice by shaping the gut microbiome composition and 5-HT metabolism. However, little research has explored the synergistic effects of probiotics and natural mental health-improving products. In this study, three natural products (saffron, l-theanine, and phosphatidylserine), either individually or in combination, were orally administrated for 4 weeks in chronic restraint stress (CRS)-induced mice, and their depressive behaviors, hippocampal 5-HT, and serum corticosterone were assessed. Saffron demonstrated improvement of the depressive-like behaviors via multiple behavioral tests and reversed the declined concentration of 5-HT and increased concentration of corticosterone. Following an initial screening, saffron was chosen to be combined with WHH2078, referred to as WHHMOOD™. Furthermore, the effects of WHHMOOD were evaluated in mice with depressive-like behaviors. WHHMOOD reduced immobility time in the forced swimming test and tail suspension test, increased the time spent in the central area in open field test, and reduced the serum corticosterone level. Besides, WHHMOOD improved the CRS-induced gut microbial dysbiosis by reversing gut microbial diversity and the abundances of Ligilactobacillus, Candidatus Arthromitus, and Erysipelatoclostridium. Compared to WHH2078, WHHMOOD treatment significantly increased the travel distance and hippocampal 5-HT level in mice. In conclusion, WHHMOOD exhibited prophylactic effects on depressive-like in CRS mice, which may act as a promising agent for improving the symptoms of depression., (© 2024 Institute of Food Technologists.)

Depression currently ranks as the fourth leading cause of disability globally, affecting approximately 20% of the world's population. we established a chronic restraint stress (CRS) induced depression model in mice and employed fluoxetine as a reference drug. We assessed the therapeutic potential of saffron essential oil (SEO) and elucidated its underlying mechanisms through behavioral indices and NMR-based metabolomic analysis. The findings indicate that SEO ameliorates behavioral symptoms of depression, such as the number of entries into the central area, fecal count, latency to immobility, and duration of immobility in both the Tail Suspension Test (TST) and the Forced Swim Test (FST), along with correcting the dysregulation of 5-serotonin. Metabolomic investigations identified sixteen potential biomarkers across the liver, spleen, and kidneys. SEO notably modulated nine of these biomarkers: dimethylglycine, glycerol, adenosine, β-glucose, α-glucose, uridine, mannose, sarcosine, and aspartate, with glycerol emerging as a common biomarker in both the liver and spleen. Pathway analysis suggests that these biomarkers participate in glycolysis, glycine serine threonine metabolism, and energy metabolism, potentially implicating a role in neural regulation. In summary, SEO effectively mitigates depressive-like behaviors in CRS mice, predominantly via modulation of glycolysis, amino acid metabolism, and energy metabolism, and potentially exerts antidepressant effects through neural regulation. Our study offers insights into small molecule metabolite alterations in CRS mice through a metabolomics lens, providing evidence for the antidepressant potential of plant essential oils and contributing to our understanding of the mechanisms of traditional Chinese medicine in treating depression., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ying Zhou reports financial support was provided by Zhejiang University of Technology. Ziwei Chen reports financial support was provided by Zhejiang University of Technology. Feng Su reports financial support was provided by Zhejiang University of Technology. Yi Tao reports financial support was provided by Zhejiang University of Technology. Ping Wang reports financial support was provided by Zhejiang University of Technology. Jinping Gu reports financial support was provided by Zhejiang University of Technology. Ying Zhou, Ziwei Chen, Feng Su,Yi Tao reports a relationship with Zhejiang University of Technology that includes: employment. Ping Wang, Jinping Gu reports a relationship with Zhejiang University of Technology that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A predictive model utilizing near-infrared spectroscopy was developed to estimate the loss on drying, total contents of crocin I and crocin II, and picrocrocin content of saffron. Initially, the LD values were determined using a moisture-ash analyzer, while HPLC was employed for measuring the total contents of crocin I, crocin II, and picrocrocin. The near-infrared spectra of 928 saffron samples were collected and preprocessed using first derivative, standard normal variable transformation, detrended correction, multivariate scattering correction, Savitzky-Golay smoothing, and mean centering methods. Leveraging the partial least squares method, regression models were constructed, with parameters optimized through a selective combination of the above six preprocessing methods. Subsequently, prediction models for loss on drying, total contents of crocin I and crocin II, and picrocrocin content were established, and the prediction accuracy of the models was verified. The correlation coefficients and root mean square error of loss on drying, total contents of crocin I and crocin II, and picrocrocin content demonstrated high accuracy, with R 2 values of 0.8627, 0.8851, and 0.8592 and root mean square error values of 0.0260, 0.0682, and 0.0465. This near-infrared prediction model established in the present study offers a precise and efficient means of assessing loss on drying, total contents of crocin I and crocin II, and picrocrocin content in saffron and is useful for the development of a rapid quality evaluation system.

Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds., (© 2024. The Author(s).)

Experimental evidence indicates that the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and MK-801 induce schizophrenia-like symptoms in rodents, including cognitive deficits. Crocins are among the active components of the plant Crocus sativus L. and were found to be effective in different models of psychiatric disorders comprising schizophrenia. The present study was designed to evaluate the efficacy of the joint administration of sub-effective doses of crocins with those of the atypical antipsychotics clozapine and risperidone in alleviating nonspatial recognition and emotional memory deficits induced either by ketamine (3 mg/kg) or MK-801 (0.1 mg/kg) in the rat. To this end, the object recognition and the step-through passive avoidance tests were used. Co-administration of sub-effective doses of crocins (5 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) counteracted nonspatial recognition and emotional memory deficits induced by NMDA receptor antagonists. The current findings suggest that this combinatorial treatment was efficacious in attenuating cognitive impairments related to the blockade of the NMDA receptor. In addition, the present results support the potential of crocins as an adjunctive drug for the therapy of schizophrenia., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Trypsin is a serine protease, an important digestive enzyme that digests the proteins in the small intestine. In the present study, we have investigated the interaction of safranal, a major saffron metabolite, with trypsin using spectroscopic and molecular docking analyses. Fluorescence emission spectra of trypsin were largely affected by the inner filter effect from safranal; that's why these were corrected using the standard procedure. The corrected fluorescence spectra have shown that the safranal quenched the intrinsic fluorescence of trypsin with a blue shift in the wavelength of emission maximum, which revealed that the microenvironment of the fluorophore became more hydrophobic. There was approximately 1: 1 fair binding between them, which increased with a rise in temperature. The interaction was favored, principally, by hydrophobic forces, and there was an efficient energy transfer from the fluorophore to the safranal. Synchronous fluorescence spectra suggested that the tryptophan residues were the major ones taking part in the fluorescence quenching of trypsin. Safranal also influenced the secondary structure of trypsin and caused partial unfolding. Molecular Docking and the Molecular Dynamics simulation of the free and complexed trypsin was also carried out. Safranal formed a stable, non-covalent complex within the S2'-S5' subsite. Moreover, two nearby tyrosine residues (Tyr39 and Tyr151) stabilized safranal through π-π interactions. Additionally, the presence of safranal led to changes in the protein flexibility and compactness, which could indicate changes in the surrounding of tryptophan residues, impacting their fluorescence. Furthermore, a loss in compactness is in line with the partial unfolding observed experimentally. Thus, both experimental and computational studies were in good agreement with each other., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Smoking is one of the main causes of death in the world. Cigarette use is related with various components of metabolic syndrome (e.g., insulin resistance, raised blood pressure, dyslipidemia, oxidative stress, inflammation state) and psychiatric disorders. This study was conducted to determine the effect of crocin (Cro) supplementation on nicotine dependence, anxiety, depression, and metabolic indices in smokers. A total of 50 smokers were selected and randomly categorized into two groups (crocin and placebo). The intervention group received crocin (30 mg per day; n = 25) and placebo (containing Avicel; n = 25) once a day. The primary (nicotine dependence, depression, and anxiety inventory) and secondary (metabolic indices) outcomes were assessed at the start of the intervention and after the 3 months. Multiple linear regression models were used to assess the treatment effects on the outcomes adjusting for confounding variables. The primary outcome results such as nicotine dependence, depression, and anxiety inventory did not have a significant difference among the intervention groups (P > 0.05). Also in the secondary outcomes, fasting plasma glucose (FPG), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) levels did indicate a significant difference by Cro intervention (β - 3.27 mg/dL; 95% CI, - 5.23, - 1.31; P = 0.002; β - 0.76 μIU/mL; 95% CI, - 1.38, - 0.15; P = 0.01; β - 0.18; 95% CI, - 0.29, - 0.07; P = 0.002), respectively. There were also significant reductions in serum levels of high-sensitivity C-reactive protein (hs-CRP) (β - 0.72 mg/L; 95% CI, - 1.37, - 0.07; P = 0.03), compared with the placebo. Cro intake may have favorable effects on the level of FPG, insulin, HOMA-IR, and hs-CRP in smokers. However, due to the small sample size and limited scientific reports on smokers, further studies are necessary. ClinicalTrial.gov Identifier: IRCT20170420033551N11., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Crocus sativus L., commonly known as saffron, is a precious spice coming from Asia, in particular from Iran, the country leader in its production. The spice is derived exclusively from dried stigmas and it is the most expensive one in the world. The areas of application of saffron are multiple, in fact ranging across the food, drinks, pharmaceuticals and cosmetics sectors. As is the case with other phytochemicals, not only the final product but also saffron by-products are considered a valuable source of bioactive natural compounds. In fact, its healthy effects, especially as antioxidants and anti-inflammatories (via reducing pro-inflammatory cytokines), are well-recognized in internal medicine. In particular, its healthy effects are related to counteracting degenerative maculopathy, depression and anxiety, neurodegenerative diseases, metabolic syndrome, cancer and chronic kidney disease, by promoting glucose metabolism. In this review, we summarize the most important papers in which saffron has turned out to be a valuable ally in the prevention and treatment of these pathologies. Moreover, we would like to promote the use of saffron by-products as part of a bio-circular economy system, aimed at reducing wastes, at maximizing the use of resources and at promoting environmental and economic sustainability.

Saffron, the dried stigma of Crocus sativus L., is a renowned spice and medicinal herb. During its production, a significant amount of floral residues, rich in bioactive compounds, are discarded as agricultural by-products. This study presents a novel approach to the sustainable utilization of these stigmaless floral residues (FRC) by optimizing the extraction and purification of their flavonoids, analyzing their chemical composition, and evaluating their effect on glucose uptake. The extraction of flavonoids from FRC was optimized using single-factor experiments and response surface methodology. The optimal conditions for extraction were an ethanol concentration of 67.7%, a temperature of 67.6 °C, a solid-to-liquid ratio of 1:30, an extraction time of 3 h, and two extractions. The crude extract obtained was then purified using macroporous resin HPD100, selected after comparing the adsorption and desorption characteristics of six different resins. The optimal purification parameters were an adsorption concentration of 40 mg/mL, a loading volume of 7 bed volumes (BV) at a flow rate of 3 BV/h, and 80% ethanol as the eluent with a volume of 4 BV. The resulting flavonoid-enriched extract (FFRC) had an experimental yield of 8.67% ± 0.01 and a flavonoid content of 128.30 ± 4.64 mg/g. The main flavonoids in FFRC were identified as kaempferol glycosides, isorhamnetin glycosides, and quercetin glycosides. Moreover, FFRC significantly stimulated glucose consumption and uptake in C2C12 myotubes, suggesting its potential utility as a natural hypoglycemic agent. This study contributes to the sustainable and value-added utilization of agricultural resources by providing data for the exploitation and application of flavonoids from saffron by-products.

Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus (Cr) plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Cr tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling, and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications., (© 2024 International Union of Biochemistry and Molecular Biology.)

Introduction-Background: Data from experimental trials show that Crocus sativus L. (saffron) is considered to improve glycemia, lipid profile, and blood pressure and reduce oxidative stress. So far, clinical trials have been conducted in individuals with metabolic syndrome and Diabetes Mellitus type 2 (DMT-2). The purpose of this study is to assess the effectiveness of saffron in individuals with Diabetes Mellitus type 1 (DMT-1)., Patients-Methods: 61 individuals with DMT-1, mean age 48 years old (48.3 ± 14.6), 26 females (42.6%) were randomized to receive a new oral supplement in sachets containing probiotics, prebiotics, magnesium, and Crocus sativus L. extract or placebo containing probiotics, prebiotics and magnesium daily for 6 months. Glycemic control was assessed with a continuous glucose monitoring system and laboratory measurement of HbA1c and lipid profile was also examined. Blood pressure at baseline and end of intervention was also measured. Individuals were either on a continuous subcutaneous insulin infusion with an insulin pump or in multiple daily injection regimens. Diabetes distress and satiety were assessed through a questionnaire and body composition was assessed with bioelectrical impedance., Results: At the end of the intervention, the two groups differed significantly only in serum triglycerides ( p = 0.049). After 6 months of treatment, a significant reduction in the active group was observed in glycated hemoglobin ( p = 0.046) and serum triglycerides ( p = 0.021) compared to baseline. The other primary endpoints (glycemic control, lipid profile, blood pressure) did not differ within the groups from baseline to end of intervention, and there was no significant difference between the two groups. Diabetes distress score improved significantly only in the active group ( p = 0.044), suggesting an overall improvement in diabetes disease burden in these individuals but that was not significant enough between the two groups., Conclusions: A probiotic supplement with saffron extract improves serum triglycerides in well-controlled people with DMT-1 and may potentially be a valuable adjunct for enhancing glycemic control.

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 ( 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.

Breast cancer (BC) is the most prevalent malignancy in women and the second most common disease worldwide, affecting approximately one million individuals annually. Despite the efficacy of conventional chemotherapy, medication resistance and adverse effects limit its effectiveness, leading researchers to explore alternative treatments, including herbal remedies. Saffron, a well-known spice derived from the Crocus sativus L. plant, has shown potential as a BC treatment. The active components of saffron exhibit anti-cancer properties by inducing apoptosis, inhibiting cell division, and modulating signaling pathways implicated in cancer development, such as PI3K/AKT, NF-κB, and MAPK. Clinical findings suggest that saffron can alleviate chemotherapy-induced symptoms, reduce serum tumor marker levels, and enhance quality of life. Preliminary clinical trials are investigating the safety and efficacy of saffron in treating BC, with recent evidence indicating that recommended doses of saffron supplementation are well-tolerated and safe. This review provides an overview of the anti-tumor effects of saffron and its unique chemical composition in BC. However, further research and clinical studies are imperative to fully comprehend the potential of saffron in adjuvant therapy for BC patients., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal., (© 2024 John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Crocus sativus L. known as saffron, is a popular food condiment with a high aroma, deep colour, and long and thick threads (stigmas) cultivated in Iran, Morocco, Spain, Italy, China, Japan, France, Turkey, and India. In 'Ayurveda', saffron is acknowledged for its immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactagogue, febrifuge, sedative, relaxant, and anxiolytic activities. The renowned Persian physician and philosopher, Avicenna, delineated saffron as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilator, and aphrodisiac in his book, the Canon of Medicine. Within traditional Iranian Medicine (TIM), saffron is characterized as a mood elevator and a rejuvenator for the body and senses. Further, the ethnopharmacological evidence indicates that saffron has shown an effect against neurodegenerative disorders namely, dementia, Alzheimer's, and Parkinson's with its bioactive constituents i.e., carotenoids and apocarotenoids., Aim: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aβ) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect., Methods: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aβ plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE., Results: Scopolamine produces memory impairment, and its chronic administration forms Aβ plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment., Conclusion: Supplementation with CSE significantly attenuates the formation of Aβ plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The dried stigmas of Crocus sativus L. produce saffron, a precious spice used for its culinary and medicinal properties since ancient times, while its petals are considered the main by-product of saffron production. The present study aimed to comparatively evaluate the phenolic content, antioxidant capacity, and antibacterial activity of methanolic extracts of stigmas and petals of Crocus sativus L. from Taliouine. The polyphenol content was measured using the Folin-Ciocalteu method, the antioxidant activity was determined using the DPPH free radical scavenging method, and the well-diffusion method was used to assess antibacterial activity against seven pathogenic bacterial strains ( Bacillus subtilis, Escherichia coli, Listeria monocytogenes, Proteus vulgaris , Pseudomonas aeruginosa, Salmonella enterica , and Staphylococcus aureus ). Furthermore, the minimum inhibitory concentration (MIC) of the extracts was determined using the microdilution broth test. Our findings revealed that stigmas and petals contained phenolic compounds at the rate of 56.11 ± 4.70 and 64.73 ± 3.42 mg GAE/g, as well as DPPH radical scavenging capacity with IC 50 of 1700  µ g/ml and 430  µ g/ml, respectively. Petal extract showed more effective antibacterial activity, with inhibition diameters ranging from 10.66 ± 0.57 to 22.00 ± 1.00 mm and MIC values ranging from 2.81 to 5.62 mg/ml, compared to the stigma extract, which displayed inhibition diameters from 10.00 ± 0.00 to 18.67 ± 0.76 mm and MIC from 2.81 to 11.25 mg/ml, against five of the seven bacterial strains tested, including S. aureus, E. coli, P. vulgaris, P. aeruginosa, and S. enterica . Statistical analyses were performed to determine the significance of these results. Thus, stigmas and petals of Crocus sativus L. might serve as a suitable source of natural antioxidant and antimicrobial agents for application in the food and pharmaceutical industries., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Asmaa Benkerroum et al.)

Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health. Among them, crocin is the most abundant and characteristic constituent of saffron, responsible for its bright red color and antioxidant properties. One of the most promising applications of saffron and its constituents is in the prevention and treatment of neurological disorders, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, and other brain disorders. Saffron and its constituents have been reported to exert neuroprotective effects through various mechanisms, such as modulating neurotransmitters, enhancing neurogenesis, reducing neuroinflammation, regulating oxidative stress, activating the Nrf2 signaling pathway, and modulating epigenetic factors. Several clinical and preclinical studies have demonstrated the efficacy and safety of saffron and its constituents in improving cognitive function, mood, and other neurological outcomes. In this review, we summarize the current evidence on the therapeutic potential of saffron and its constituents in neurological disorders, from bench to bedside. We also discuss the challenges and future directions for the development of saffron-based therapies for brain health., (© 2024 John Wiley & Sons Ltd.)

Among various herbal plants, saffron has been the subject of study in various medical and food fields. Among the compounds of saffron, safranal is one of them. Safranal is a monoterpene aldehyde. The precursor of safranal is called picrocrocin, whose hydrolysis leads to the production of safranal. picrocrocin has two sugar components and aglycone. sugar component was separated during the drying process of saffron and safranal is produced. Saffron is the cause of the saffron aroma. Previous studies have shown that safranal offers many benefits such as antioxidants, blood pressure regulation and anti-tumor qualities. On the other hand, α-Chy is an enzyme secreted by the pancreas into the intestine and then acts as an efficient protease. In this study, various methods, such as molecular dynamics (MD) simulation and molecular binding, and different spectroscopic techniques, as well as protein stability techniques, were used to investigate the possible interactions between safranal and α-Chy. UV spectroscopic studies were showing that the existence of safranal decreased α-Chy absorption intensity. safranal caused the intrinsic fluorescence of α-Chy to be quenched too. According to the Stern-Volmer equation, the interaction between safranal and α-Chy was of the static type. In thermodynamic calculations, the interaction between safranal and α-Chy was stabilized by hydrophobic forces. And it was found that this interaction continued spontaneously. These results were, thus, consistent with the Docking data simulation (with the negative ΔG° number and positive changes in enthalpy and entropy). The thermal stability of α-Chy was also measured, showing that its melting point was shifted to a higher threshold as a result of the interaction. also, MD simulation indicated that α-Chy became more stable in the presence of safranal. In this paper, all the results of the laboratory techniques were confirmed by molecular dynamic simulations, so the correctness of the results was confirmed. From this research, we hope to carefully observe the possible changes in the behavior and structure of the enzyme in the presence of safranal.Communicated by Ramaswamy H. Sarma.

Saffron (Crocus sativus), as an herbal medicine, has been extensively investigated for treating neurological and psychiatric disorders. This systematic review aimed to assess the overall effects of saffron on cognition, depression, anxiety, sleep disorders, attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Relevant randomized controlled trials (RCTs) were identified by searching PubMed/Medline, Web of Science, and Clinical Trials databases up to June 2023 according to search terms and inclusion criteria. The participants were either healthy or suffering from some diseases, including neurological and psychiatric disorders, and consumed saffron or its extracts as an intervention. The risk of bias was assessed according to the Cochrane guidelines, and the PRISMA statement was followed. The meta-analysis was performed using RevMan and STATA software. A random-effects or fixed-effects model was used to calculate the pooled effect sizes. Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs. Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93). Saffron was non-inferior to conventional drugs for treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it exhibited good tolerance with few side effects. Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment., (© 2024 John Wiley & Sons, Ltd.)

To explore the mechanisms affecting the biopharmacological properties of the active components of saffron. Ultrasonic extraction technique was applied to extract the active components from safflower materials and combined with molecular docking technique to screen four safflower anti-inflammatory active components, naiophenol-3-0-rutinoside, kaempferol-3-O-glucoside, quercetin and lignan. In order to understand the mechanism of the influence of its biopharmaceutical properties, the changes of the solubility and permeability parameters of the anti-inflammatory active components of safflower were obtained by using the classical shaking bottle method and the body enteric irrigation method. The compound environment had a great influence on the solubility of single active ingredient. The calculated results of the dose number of all ingredients were greater than 1, and the solubility properties were all high solubility. The absorption parameters and osmotic coefficients of kaempferol-3-O-glucoside and lignan varied insignificantly under different concentration conditions, while each osmotic coefficient of kaempferol-3-O-rutinoside and quercetin showed a positive proportional decreasing trend. In addition, the osmotic coefficients of the three components except kaempferol-3-O-glucoside did not change with environmental changes, and the overall anti-inflammatory active ingredient absorption mechanisms included both passive diffusion and active transport. The two biopharmaceutical properties of the solubility and permeability of the active ingredients of Safflower can be changed under the influence of the application environment and drug concentration. In the pharmaceutical process, the preparation means can be optimized from this aspect to achieve the purpose of improving the clinical efficacy of Safflower anti-inflammatory drugs.

Crocins are glucosylated apocarotenoids present in flowers and fruits of a few plant species, including saffron, gardenia, and Buddleja. The biosynthesis of crocins in these plants has been unraveled, and the enzymes engineered for the production of crocins in heterologous systems. Mullein (Verbascum sp.) has been identified as a new source of crocins and picrocrocin. In this work, we have identified eight enzymes involved in the cleavage of carotenoids in two Verbascum species, V. giganteum and V. sinuatum. Four of them were homologous to the previously identified BdCCD4.1 and BdCCD4.3 from Buddleja, involved in the biosynthesis of crocins. These enzymes were analyzed for apocarotenogenic activity in bacteria and Nicotiana benthamiana plants using a virus-driven system. Metabolic analyses of bacterial extracts and N. benthamiana leaves showed the efficient activity of these enzymes to produce crocins using β-carotene and zeaxanthin as substrates. Accumulations of 0.17% of crocins in N. benthamiana dry leaves were reached in only 2 weeks using a recombinant virus expressing VgCCD4.1, similar to the amounts previously produced using the canonical saffron CsCCD2L. The identification of these enzymes, which display a particularly broad substrate spectrum, opens new avenues for apocarotenoid biotechnological production., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Nicotine is a psychostimulant that induces neurochemical and behavioral changes upon chronic administration, leading to neurodegenerative conditions associated with smoking. As of now, no preventive or therapeutic strategies are known to counteract nicotine‑induced neurodegeneration. In this study, we explore the neuroprotective effects of crocin, a bioactive agent commonly found in saffron - a spice derived from the flower of Crocus sativus - using a rat model. The dose‑dependent effects of crocin were evaluated in nicotine‑induced neurodegeneration and compared with a control group. Neurobehavioral changes, assessed through the elevated plus maze, the open field test, the forced swim test, and the Morris water maze, as well as oxidative stress in the hippocampus, were evaluated. Interestingly, nicotine administration resulted in depression, anxiety, and abnormal motor and cognitive functions, while crocin treatment protected the rat brain from these abnormalities. The beneficial effects of crocin were associated with reduced oxidative stress biomarkers such as malondialdehyde, along with increases in superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. These results demonstrate that crocin can mitigate nicotine‑induced neurodegeneration by reducing oxidative stress, potentially offering a protective measure against neurodegenerative effects in smokers.