In vitro and in vivo evaluation of the diabetic wound healing properties of Saffron (Crocus Sativus L.) petals.

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.

Saffron (Crocus sativus L.) and Its By-Products: Healthy Effects in Internal Medicine.

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.

Optimization of Extraction and Purification of Flavonoids from Stigmaless Floral Residues of Crocus sativus L. and Their Stimulatory Effect on Glucose Uptake In Vitro.

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.

Effect of Crocus sativus Extract Supplementation in the Metabolic Control of People with Diabetes Mellitus Type 1: A Double-Blind Randomized Placebo-Controlled Trial.

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.

Dissecting the binding effect of Crocetin glucosyltransferase 2 in crocetin biotransformation in saffron (Crocus sativus L.) from different origins.

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.

Geographical authentication of saffron by chemometrics applied to the ion mobility spectrometry data.

There is a lack of a reliable tool for quickly determining the geographical origins of saffron (SFR). Ion mobility spectrometry (IMS) has emerged as a promising method for rapid authentication. In this study, 232 Iranian SFR samples harvested in five distinct areas (Khorasan, Azerbaijan, Golestan, Fars, and Isfahan) were analyzed by IMS coupled with chemometric methods. The principal component analysis (PCA) was applied for analyzing the collected IMS data, utilizing three principle components (PCs) that accounted for 81 % of the explained variance. Moreover, the partial least squares-discriminant analysis (PLS-DA) demonstrated the average sensitivity and specificity rates, of 72.3 % to 92.5 % for the exernal test set and 75.5 % to 94.3 % for training set. The accuracy values were ≥ 85.0 % for the prediction set for all classes of samples. The results of this study revealed a successful application of IMS and chemometric methods for rapid geographical authentication of saffron samples in Iran.

Effects of Crocus sativus L. Floral Bio-Residues Related to Skin Protection.

The cultivation of Crocus sativus L. to obtain the saffron spice generates a large amount of biowaste, constituted mainly by the flower's tepals. The aim of this work was to evaluate the antioxidant and dermo-protective effect of a complex methanolic extract of C. sativus tepals. The extract's major phenolic content was analyzed using ultra-high performance liquid chromatography with electrospray ionization, coupled with quadrupole-time-of-flight-mass spectrometry (UHPLC-ESI-QTOF-MS). Then, the antioxidant in vitro activity of the extract was studied and related to their chemical composition. Likewise, the effect on intracellular ROS levels in HepG2 and Hs27 cell culture was determined in normal culture and under hydrogen-peroxide-induced oxidative stress. Finally, tyrosinase, hyaluronidase, collagenase, elastase, and xanthine oxidase assays were carried out to determine the dermo-protective capacity of the extract. The high polyphenol content, including flavonoids and anthocyanins, explains the antioxidant effect of the extract both in vitro and in culture assays. The extract has a significant and remarkable protective capacity against oxidative stress induced in culture of the two studied cell lines. It is also remarkable in its ability to inhibit hyaluronidase, tyrosinase, and xanthine oxidase. Results pointed out this biowaste extract as a promising ingredient in the composition of cosmetics.

Identification and Functional Validation of Two Novel Antioxidant Peptides in Saffron.

Saffron (Crocus sativus L.) is one of the most expensive spices in the world, boasting rich medicinal and edible value. However, the effective development of active natural substances in saffron is still limited. Currently, there is a lack of comprehensive studies on the saffron stigma protein, and the main effect peptides have not been identified. In this study, the total protein composition of saffron stigmas was analyzed, and two main antioxidant peptides (DGGSDYLGK and VDPYFNK) were identified, which showed high antioxidant activity. Then, the stability of two peptides was further evaluated. Furthermore, our results suggested that these two peptides may protect HepG2 cells from H2O2-induced oxidative damage by significantly improving the activity of endogenous antioxidant enzymes and reducing the malondialdehyde (MDA) content. Collectively, we identified two peptides screened from the saffron protein possessing good antioxidant activity and stability, making them promising candidates for use as functional foods, etc., for health promotion. Our findings indicated that proteomic analysis together with peptide identification is a good method for exploitation and utilization of spice plants.

"Plant Golden" C. sativus: Qualitative and quantitative analysis of major components in stigmas and petals and their biological activity in vitro.

Crocus sativus L. (C. sativus) has its stigma as the main valuable part used. With extremely low production and high prices, stigma is considered a scarce resource. As a result, its petals, considered as by-products, are often discarded, leading to significant waste. We developed a UPLC-Q-Orbitrap HRMS method for qualitative analysis of stigmas and petals and a UHPLC-QQQ-MS/MS method for simultaneous quantification of 9 characteristic active compounds for the first time, and compared their biological activity in vitro. The results indicated that a total of 63 compounds were identified in the petals and stigmas. The content of flavonoids in the petals was significantly superior to that in the stigma, and the content of quercetin in the petals was 50 times higher than that in the stigma. The results of the in vitro evaluation of biological activity indicated that both the petals （•OH: IC50=39.70 mg/mL; DPPH: IC50=28.37 mg/mL; ABTS: IC50=0.9868 mg/mL）and stigma （•OH: IC50=34.41 mg/mL; DPPH: IC50=38.99 mg/mL; ABTS: IC50=3.194 mg/mL）demonstrated comparable antioxidant activities. However, the tyrosinase inhibitory activity in petals （IC50=21.17 mg/mL） was weaker than that in stigma（IC50=1.488 mg/mL）. This study provides a fast, reliable, and efficient analytical method that can be used for the quality assessment of petals as a natural resource and its related products in the food and pharmaceutical industries.

Mining of disease-resistance genes in Crocus sativus based on transcriptome sequencing.

Introduction: Crocus sativus L. has an important medicinal and economic value in traditional perennial Chinese medicine. However, due to its unique growth characteristics, during cultivation it is highly susceptible to disease. The absence of effective resistance genes restricts us to breed new resistant varieties of C. sativus. Methods: In present study, comprehensive transcriptome sequencing was introduced to explore the disease resistance of the candidate gene in healthy and corm rot-infected C. sativus. Results and discussion: Totally, 43.72 Gb of clean data was obtained from the assembly to generate 65,337 unigenes. By comparing the gene expression levels, 7,575 differentially expressed genes (DEGs) were primarily screened. A majority of the DEGs were completely in charge of defense and metabolism, and 152 of them were annotated as pathogen recognition genes (PRGs) based on the PGRdb dataset. The expression of some transcription factors including NAC, MYB, and WRKY members, changed significantly based on the dataset of transcriptome sequencing. Therefore, this study provides us some valuable information for exploring candidate genes involved in the disease resistance in C. sativus.

Saffron (Crocus sativus L.) extract attenuates chronic scopolamine-induced cognitive impairment, amyloid beta, and neurofibrillary tangles accumulation in rats.

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 (Aß) 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 Aß 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 Aß 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 Aß plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.

Analysis of tissue distribution of metabolites in Crocus sativus L. corms based on DESI mass spectrometry imaging technique / 药学实践与服务

Objective To explore the distribution characteristics of endogenous metabolites in Crocus sativus L. corms from different origins. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. sativus corms. Results In situ characterization of metabolites such as flavonoids, organic acids, amino acids, carotenoids, and cyclic enol ether terpene glycosides was achieved. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Apigenin 7-（6''-O-acetyl）-glucoside, isorhamnetin-3-O-β-D-Glucoside, dhurrin 6'-glucoside, and Apigenin 7-O-diglucuronide were mainly distributed in the terminal bud. For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. Conclusion The distribution of metabolites in different parts of C. sativus corms from different origins and the same origin varies significantly. Flavonoids and flavonoid derivatives such as isorhamnetin-3-O-β-D-Glucoside and apigenin derivatives are mainly distributed in the terminal buds, in addition, the natural plant protection agent dhurrin 6'-glucoside is also mainly distributed in the terminal corms, whereas amino acids, which are used as energy and material supplies, are mainly accumulated in the corms.

Effectiveness of the Combination of Probiotic Supplementation on Motor Symptoms and Constipation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) reflects the second most common neurodegenerative disorder and is associated with high morbidity and mortality. Besides the motor features, non-motor symptoms, such as constipation, are very common. There is accumulating evidence that neuroinflammation is associated with the PD pathological processes. Alterations of gut microbiota and microbial metabolites have been linked to the pathogenesis of PD. Previous research has shown that probiotic supplementation has beneficial effects on motor and non-motor symptoms and especially on constipation. AIM: In this study, we examine the effectiveness of a combination of probiotic supplementation (butyrate triglyceride 302.86 mg, Crocus sativus L. 30 mg, and vitamin D3 100 mcg), on constipation and motor symptoms in PD. METHODS: The present study is a retrospective study that examined the existing medical records of patients with diagnosed PD, having chronic constipation and used the probiotic supplementation for its management. A total of 41 existing medical records were screened. Medical records were excluded in the case of participation in another study for PD, suffering from irritable bowel syndrome, organic constipation, long-term laxative use changes in the standard dopaminergic treatment, Mini-Mental Status Examination (MMSE) score<24, hospitalization and antibiotic medication, and diarrheal syndrome. Nine medical records were excluded, and a final number of 32 medical records was finally examined. All 32 patients had evaluations carried out at baseline and three months after supplement administration. A stool diary questionnaire, the Unified Parkinson's Disease Rating Scale III (UPDRS III), and the Schwab and England and the Hoehn and Yahr scales were used for the evaluation. RESULTS: The median defecation frequency was significantly improved. The supplementation administration significantly improved UPDRS III by 7.7% (from 35.72±15.51 to 32.97±15.71, p = 0.005) at month three, as compared to baseline. A positive effect was also seen in the Schwab and England scale. There was no effect on the Hoehn and Yahr scale. CONCLUSION: The enteric microbiome composition is altered in PD, and there is accumulating evidence that probiotic supplementation could alleviate disease symptoms in neuroinflammatory disorders.

Detection of botanical adulterants in saffron powder.

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

Saffron and Sleep Quality: A Systematic Review of Randomized Controlled Trials.

Background: Sleep quality is defined as an individual's consent to sleep experience. Poor sleep quality has important adverse health outcomes. There are drugs to treat sleep disorders but consumption of these drugs is accompanied by adverse effects whereas herbal treatments have fewer side effects. Saffron is spice obtained from Crocus sativus flower. Several articles have been done on its effects on the quality of sleep and its safety. This review for the first time critically evaluates effect of saffron on sleep quality improvement. Method: The search technique aims to get all related published data-based up to 2022 articles. PubMed, Central, Google Scholar, and Scopus were examined. Only full reports were evaluated (abstracts were excluded). The first screening was done by title and abstract. Then full text of articles was read and irrelevant articles were removed. Duplicate articles were also removed by Endnote. By using Cochrane risk of bias tool assessment, a quality score based on probability of bias was given. Methodological characteristics were also evaluated using the criteria of Stevinson and Ernst. Result: In the systematic review, 5 randomized clinical trials with 379 participants from 3 countries were identified. In placebo-comparison trials, saffron contains a large treatment. Conclusion: It seems that saffron has a beneficial influence on duration and quality of sleep. Saffron, crocin, and safranal induce hypnotic effects by increasing the duration of sleep. Research conducted so far provides initial support and safety for use of saffron to improve sleep quality.

Evaluation of Saffron (Crocus Sativus L) Effects on Anxiety in Hospitalized Patients with Acute Coronary Syndrome.

Background: Anxiety is a common psychiatric condition in cardio-vascular diseases. Saffron appears to have a wide range of therapeutic effects on psychiatric conditions and cardio-vascular disorders. The aim of this study was to determine the effect of saffron on anxiety in hospitalized patients with acute coronary syndrome (ACS). Materials and Methods: In this clinical investigation, we selected 80 patients with ACS from Tohid Medical Center, Sanandaj. Patients were divided randomly into two groups, intervention group (n = 41), and control group (n = 39), based on how they received saffron and placebo every 12 hours for 4 days, respectively. The Spielberger Anxiety Inventory was completed before and after the intervention in both groups. Results: There was no significant difference between the intervention and control groups regarding the mean scores of the trait and state anxiety before and after the intervention (P > 0.05). Conclusion: The present study did not corroborate the therapeutic effects of saffron on reducing anxiety in patients with ACS.

Crocus sativus Extract as a Biological Agent for Disease-Modifying Therapy of Collagenase-Induced Mouse Model of Osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is an age-related joint disease that involves the degeneration of cartilage and is the most prevalent form of arthritis, affecting a large part of the population. OA is a multifactorial disorder, and no single etiological mechanism has been found to be common to all forms of the disease. Currently used therapies for control of the disease are mainly nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid medications. The aim of this study was to investigate the extract from Crocus sativus as a biological disease-suppressing therapy agent. METHODS: Balb/c mice were injected intra-articularly with Clostridium histolyticum type IA for induction of osteoarthritis. The mice were randomized to five groups: control group, I group (CIOA untreated), II group (CIOA + 100 mg/kg/daily saffron), III group (CIOA + 50 mg/kg/daily saffron), IV group (CIOA + 25 mg/kg/daily saffron). Flow-cytometry analysis was used to study the splenocytes' phenotype isolated from the treated animals. The serum levels of inflammatory and anti-inflammatory cytokines were analyzed with ELISA. The histological assessment was used to analyze the saffron extract effect on histopathological alterations. RESULTS: Saffron treatment significantly decreased osteoarthritis-associated joint histological manifestations and decreased serum TNFα levels. The flow-cytometry analysis showed a decrease in pro-inflammatory immune cell subtypes in the spleen. CONCLUSIONS: The results obtained suggest that saffron affected the disease progression and could be a potential therapeutic approach in osteoarthritic patients' therapy.

Identification of Compounds of Crocus sativus by GC-MS and HPLC/UV-ESI-MS and Evaluation of Their Antioxidant, Antimicrobial, Anticoagulant, and Antidiabetic Properties.

In order to valorize the species Crocus sativus from Morocco and to prepare new products with high added value that can be used in the food and pharmaceutical industry, our interest was focused on the phytochemical characterization and the biological and pharmacological properties of the stigmas of this plant. For this purpose, the essential oil of this species, extracted by hydrodistillation and then analyzed by GC-MS, revealed a predominance of phorone (12.90%); (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol (11.65%); isopropyl palmitate (9.68%); dihydro-ß-ionone (8.62%); safranal (6.39%); trans-ß-ionone (4.81%); 4-keto-isophorone (4.72%); and 1-eicosanol (4.55%) as the major compounds. The extraction of phenolic compounds was performed by decoction and Soxhlet extraction. The results of the determination of flavonoids, total polyphenols, condensed tannins, and hydrolyzable tannins determined by spectrophotometric methods on aqueous and organic extracts have proved the richness of Crocus sativus in phenolic compounds. Chromatographic analysis by HPLC/UV-ESI-MS of Crocus sativus extracts revealed the presence of crocin, picrocrocin, crocetin, and safranal molecules specific to this species. The study of antioxidant activity by three methods (DPPH, FRAP, and total antioxidant capacity) has proved that C. sativus is a potential source of natural antioxidants. Antimicrobial activity of the aqueous extract (E0) was investigated by microdilution on a microplate. The results have revealed the efficacy of the aqueous extract against Acinetobacter baumannii and Shigella sp. with MIC ≤ 600 µg/mL and against Aspergillus niger, Candida kyfer, and Candida parapsilosis with MIC = 2500 µg/mL. Measurements of pro-thrombin time (PT) and activated partial thromboplastin time (aPTT) in citrated plasma obtained from routine healthy blood donors were used to determine the anticoagulant activity of aqueous extract (E0). The anticoagulant activity of the extract (E0) studied showed that this extract can significantly prolong the partial thromboplastin time (p < 0.001) with a 359 µg/mL concentration. The antihyperglycemic effect of aqueous extract was studied in albino Wistar rats. The aqueous extract (E0) showed strong in vitro inhibitory activity of α-amylase and α-glucosidase compared with acarbose. Thus, it very significantly inhibited postprandial hyperglycemia in albino Wistar rats. According to the demonstrated results, we can affirm the richness of Crocus sativus stigmas in bioactive molecules and its use in traditional medicine.

Active constituents of saffron (Crocus sativus L.) and their prospects in treating neurodegenerative diseases (Review).

Crocus sativus L. (saffron) is widely used as a traditional spice for flavoring, coloring and medicinal purposes. As a traditional Chinese herb, saffron promotes blood circulation, removes blood stasis, cools and detoxifies the blood, relieves depression and calms the mind. According to modern pharmacological studies, the active constituents of saffron, including crocetin, safranal and crocus aldehyde, exhibit antioxidant, anti-inflammatory, mitochondrial function-improving and antidepressant effects. Thus, saffron has the potential to treat neurodegenerative diseases (NDs) associated with oxidative stress, inflammation and impaired mitochondrial function, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and cerebral ischemia. The present article provides a review of the pharmacological effects of saffron and its constituents in terms of neuroprotective effects, including antioxidant and anti-inflammatory effects and the improvement of mitochondrial dysfunction, as well as their clinical application in treating NDs.

"Novel chitosan/alginate hydrogels as carriers of phenolic-enriched extracts from saffron floral by-products using natural deep eutectic solvents as green extraction media".

The current saffron production system is generating several hundreds of tons of tepal waste, because only stigmas are used for food. Consequently, the valorization of saffron floral by-products by developing stable functional ingredients could lead to the environmental impact minimization. Thus, the main aim of this study was to develop innovative green extraction processes from saffron floral by-products by using Natural Deep Eutectic Solvents (NaDES) and ultrasound-assisted extraction (UAE) as ecological extraction method. Response surface methodology was used to optimize process parameters. To improve the stability of the optimal extracts, they were incorporated into chitosan/alginate hydrogels, studying their water-uptake and water retention capacity and the total phenolic content (TPC) during the in vitro digestion. The results indicated that the optimal extraction, regarding total phenolic and flavonoid content, was achieved in 20 min, using 180 W ultrasound power and 90% of NaDES. The results of the DPPH assay revealed the potent antioxidant activity of saffron floral by-products. The chitosan/alginate hydrogels incorporating the as-obtained NaDES extracts showed favorable properties whereas the TPC remained stable under intestinal conditions. Therefore, NaDES combined with UAE was an efficient technique to isolate high added-value compounds from saffron flowers, succeeding also the valorization of discarded waste by using green and low-cost strategies. Furthermore, these novel hydrogels could be used as promising candidates for food or cosmetic applications.