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Objective(s): Olanzapine, an atypical antipsychotic, causes weight gain and metabolic disorders in humans. Safranal, one of the active components of Crocus sativus (saffron), has been shown to have anti-obesity, lipid and blood pressure lowering and anti-diabetes effects. In this investigation, the effect of safranal on metabolic disorders induced by olanzapine was studied. Materials and Methods: Fourty-two female Wistar rats were divided into 7 groups of 6 animals. The two groups were selected as controls, which received olanzapine and safranal solvents, respectively. The third group treated by olanzapine 5 mg/kg. Groups 4, 5 and 6 treated by olanzapine 5 mg/kg plus safranal (2.5, 5 and 10 mg/kg) and the last group received safranal 10 mg/kg. The injections were performed intraperitoneally for 14 days and on the 15th day the rats were killed and their serum were collected to measure metabolic factors including glucose, insulin, triglyceride, total cholesterol and HDL cholesterol. Leptin level in plasma was also measured. Mean systolic blood pressure was measured using tail cuff method at the end of study. The rats were weighed every other day and amount of food consumed was measured daily. Results: Olanzapine significantly elevated body weight, food intake, fasting blood glucose, TG, leptin, and mean systolic blood pressure (MSBP). It also significantly decreased HDL cholesterol blood level. Safranal significantly improved all these complications at three doses. Conclusion: Based on the results of this study, safranal is thought to be used as an effective combination in controlling metabolic complications caused by olanzapine. [ABSTRACT FROM AUTHOR]

The present study is designed to evaluate the therapeutic effect of Crocus sativus(saffron) aqueous extract (CSE) alone or in combination with praziquantel on Schistosoma mansoni infected mice. Parasitological, immunological, pathological and immunohistochemical parameters and surface topography of worms were determined. Treatment of S. mansoni infected mice with saffron or PZQ revealed a significant reduction in worm burden, hepatic and intestinal ova count with a decline in granuloma diameter. There was an increase in total IgG and IL-10 blood levels after treatment with PZQ and/or CSE. Superoxide dismutase (SOD) and catalase levels were improved in infected mice treated with CSE in comparison with infected mice. Male worm surface ultrastructure examination showed a swelling, rupture of numerous tubercles with marked decrease in spines and severe peeling of tegumental dorsal surfaces after treatment with saffron. In conclusion, administration of aqueous extract of Crocus sativus is effective treatment for S. mansoni infection. [ABSTRACT FROM AUTHOR]

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Introduction: Crocus sativus (saffron) is widely used in China, Iran, and India for dyeing and as a food additive and medicinal plant. Safranal, as one of the main constituents of saffron, is responsible for its aroma and has been reported to have anticancer, antioxidant, and anti-inflammation properties. Objective: In this study, we investigated the anti-inflammatory effects of Safranal in RAW264.7 cells, bone marrow-derived macrophages (BMDMs), and dextran sulfate sodium (DSS)-induced colitis mice. Methods: Safranal toxicity was determined using an MTT assay. We evaluated the inhibitory effect of nitric oxide (NO) and levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells and BMDMs. We assessed the inhibitory effect of pro-inflammatory cytokines, and the mRNA expressions of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), classical inflammatory pathways (MAPK and NF-κB), and the nuclear translocation factors AP-1 and NF-κB p65 were investigated. The in vivo anti-inflammatory effects of Safranal were assessed in a DSS-induced colitis model. DSS3.5% was used to induce colitis in mice with or without Safranal for 7 days; weight and disease activity index (DAI) were recorded daily. At the end of the experiment, the colon, mesenteric lymph nodes (MLNs), and spleen were collected for flow cytometry, ELISA, and Western blot analysis. Results: Safranal suppressed NO production, iNOS, and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BMDMs. Safranal decreased the production and mRNA expression of IL-6 and TNF-α in the RAW264.7 cell line and inhibited the phosphorylation and nuclear translocation of components of the MAPK and NF-κB pathways. Safranal alleviated clinical symptoms in the DSS-induced colitis model, and colon histology showed decreased severity of inflammation, depth of inflammatory involvement, and crypt damage. Immunohistochemical staining and flow cytometry showed reduced macrophage infiltration in colonic tissues and macrophage numbers in MLNs and the spleen. The levels of colonic IL-6 and TNF-α also decreased in Safranal-treated colitis mice. This study elucidates the anti-inflammation activity of Safranal, which may be a candidate for inflammatory bowel syndrome (IBD) therapy. [ABSTRACT FROM AUTHOR]

Background: Saffron is an interesting minor spice with a food coloring history and its active components have shown several useful pharmacological effects such as antidepressant, antiinflammatory, antitumor, radical scavenger effects, learning and memory-improving effects, anti- Alzheimer, antipruritic, etc. Because of negative consumer perception of chemical preservatives, attention is shifting towards natural alternatives. Particular interest has been focused on the potential application of plant essential oils. The aim of the present study was undertaken to evaluate the interaction of hydroalcoholic extract of saffron petals and different concentrations of it against different Gram-positive and Gram-negative bacteria. Methods: The hydroalcoholic extract of saffron petals and different concentrations of extract (60, 90, 120 mg/ml) by a blank sterilized disc diffusion test was assessed against four different grampositive and negative bacterial pathogens. Also, a full randomized factorial design experiment was conducted with three replications. The statistical analysis was performed using two-way ANOVA followed by LSD test for multiple comparisons. Results: The results of ANOVA showed that saffron petals hydroalcoholic extract and antibiotics were an effective on all tested bacterial strains and the most effective antibacterial properties has been observed on Listeria monocytogenes followed by Escherichia coli. The antibacterial activities of concentration of saffron petals hydroalcoholic extract was not significant on E. coli, but was significant on Listeria monocytogenes, Staphylococcus aureus and Salmonella typhimurium. Also, it was shown that the increases of the concentration of the extract caused higher antibacterial effects. The highest antibacterial effect of saffron petals hydroalcoholic extract was 120 mg which was observed against the L. monocytogenes. Saffron petals hydroalcoholic extract showed more antibacterial activity against the Gram-positive bacterium. Conclusion: The results of this research showed that saffron petals extract has considerable potential as a herbal-base antimicrobial compound.q [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis study evaluated the effect of saffron (Crocus sativus) on sexual dysfunction and its subscales (dimensions) among men and women. Material and Methods: PubMed/Medline, ScienceDirect, Google Scholar, as well as Scientific Information Database (www.SID.ir) and Magiran (as Persian databases) were searched without any time and language restrictions. Statistical pooling was done using the random effects model. Results: A total of 5 studies comprising 173 participants were included in this systematic review and meta-analysis. The analysis showed a statistically significant positive effect of saffron on sexual dysfunction (Std diff in means=0.811; 95% CI, 0.356-1.265) and its subscales (Std diff in means=0.493; 95% CI, 0.261-0.724). Heterogeneity indexes such as Cochran Q index and I2 indicated a heterogeneity among the included studies (Q=9:981, df:4, (p=0.041), I²=59.92%). There was no evidence of publication bias in these studies. Conclusion: In general, saffron was proven effective in improving sexual dysfunction and its subscales among participants; this effect was different on different dimensions of sexual dysfunction. Further studies are required to extend these initial findings. [ABSTRACT FROM AUTHOR]

Background: Crocus sativus, known as saffron crocus, is best known for the spice saffron. Saffron use spans more than 3500 years, however, its toxicity on neonates during lactation has not yet evaluated. Objectives: This study was aimed to examine the acute toxicity of saffron on adult mice and its nephrotoxicity and hepatotoxicity on neonates of lactating mothers that used saffron during lactation. Materials and Methods: In this experimental study, following acute toxicity evaluation, 32 pregnant mice were randomly designated into four equal groups. Following delivery, the mothers of groups 1 to 4 were administered orally (by gavage) normal saline (control group), 500, 1000 or 2000 mg/kg/day of saffron for three weeks, respectively. The newborns' kidney and liver parameters were assessed at the end of the study for possible nephrotoxicity and hepatotoxicity evaluation. The kidney and liver tissue samples of newborns were histopathologically studied after staining with Hematoxylin & Eosin. Data were analyzed using ANOVA and Scheffe's tests Results: The LD50 value of saffron was calculated to be 4120±556 mg/kg in mice. To evaluate lactating toxicity, saffron was administered orally to the mothers once daily for 21 days, after delivery, during lactating period. Saffron increased serum urea nitrogen (p< 0.05). Histological studies indicated that saffron did not have any toxic effect on liver, however, histopathology changes were seen in the kidney of neonates. Conclusions: From the results of present study, it might be concluded that saffron is a nearly safe spice, however, nursing mothers should avoid high doses of this spice. [ABSTRACT FROM AUTHOR]

Objective: Microalbuminuria and hypertension are the risk factors for diabetic nephropathy, and increased levels of liver enzymes are prevalent among diabetic patients. The aim of this research was to examine the effects of Crocus sativus supplementation on nephropathy indices, liver enzymes, and blood pressure in patients with type 2 diabetes (T2D). Materials and Methods: This placebo-controlled, randomized clinical trial was performed among 80 T2D patients. Subjects were randomly assigned to either Crocus sativus (n = 40) or placebo (n = 40) groups and treated with C. sativus and or placebo for 12 weeks, respectively. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum urea, creatinine, 24-hr urine albumin, systolic blood pressure (SBP), diastolic blood pressure (DBP), physical activity, and dietary intakes were measured and blood samples were taken at baseline and after the 12-week intervention to assess the differences between the two groups. Results: C. sativus supplementation compared with the placebo resulted in a significant reduction of SBP (P<0.005). However, changes in other indices including liver enzymes, serum creatinine, serum urea, and 24-hr urine albumin, and DBP were not significantly different between the two groups (p>0.05). Also, no significant changes in dietary intakes and physical activity were seen between the two groups. Conclusion: This report shows that daily supplementation with 100 mg C. sativus powder improved SBP. However, it did not considerably improve DBP, nephropathy indices and liver functions in T2D patients after 12 weeks of administration. [ABSTRACT FROM AUTHOR]

Summary: Saffron crocus (Crocus sativus) is the source of the most expensive spice of the world, produced from manually harvested stigmas, thus serving as a cash crop for rural communities. However, despite its economic importance, its genome and chromosomes are poorly studied. C. sativus is a sterile triploid species harboring eight chromosome triplets, and propagated only as a clonal lineage by corms. Saffron's evolutionary origin, parental species and allo‐ or autotriploidy has been a matter of discussion for almost a century.We performed a survey sequencing of the saffron genome and selected cytogenetic landmark sequences consisting of major tandem repeats, which we used as probes in comparative multicolor fluorescent in situ hybridization (FISH).We tagged 92 chromosomal positions and resolved the chromosomal composition of saffron triplets. By comparative FISH of six Crocus species from 11 accessions, we demonstrate that C. sativus is an autotriploid hybrid derived from heterogeneous Crocus cartwrightianus cytotypes.The FISH reference karyotype of saffron is crucial for integrating genome sequencing data with chromosomes and for investigating the relationship among Crocus species. We provide an evolutionary model of the saffron emergence; the knowledge of the parental origin offers a route towards the resynthesis of C. sativus from C. cartwrightianus to broaden saffron's gene pool. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes mellitus is growing rapidly worldwide. This metabolic disorder affects many physiological pathways and is a key underlying cause of a multitude of debilitating complications. There is, therefore, a critical need for effective diabetes management. Although many synthetic therapeutic glucose‐lowering agents have been developed to control glucose homeostasis, they may have unfavorable side effects or limited efficacy. Herbal‐based hypoglycemic agents present an adjunct treatment option to mitigate insulin resistance, improve glycemic control and reduce the required dose of standard antidiabetic medications. Saffron (Crocus sativus L.), whilst widely used as a food additive, is a natural product with insulin‐sensitizing and hypoglycemic effects. Saffron contains several bioactive β carotenes, which exert their pharmacological effects in various tissues without any obvious side effects. In this study, we discuss how saffron and its major components exert their hypoglycemic effects by induction of insulin sensitivity, improving insulin signaling and preventing β‐cell failure, all mechanisms combining to achieve better glycemic control. [ABSTRACT FROM AUTHOR]

This study aimed to determine optimal extraction parameters by using response surface methodology, examining the effect of microencapsulation on crocin retention, and evaluating the temperature and pH stability of crocin microcapsules. The effect of process variables on the crocin yield was successfully determined by quadratic models (R2 > 0.99 and adj R2 > 0.98). All variables significantly affected the crocin yield (P < 0.1). The process parameters, namely extraction time (4.40 min), temperature (55 °C), amplitude level (94%), and liquid to solid ratio (L/S) (1000) were determined as optimum extraction points. Safranal was shown to be a compound with major volatility in both the saffron and microcapsule extracts. Safranal, 2,4,4-trimethyl-3-carboxaldehyde-5-hydroxy-2,5-cyclohexadiene-1-one, 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde (HTCC), and isophorone were other major volatile compounds of saffron extract. The encapsulation process affected volatile percentage distribution insignificantly (P > 0.05). The thermal and pH stability of the crocin was determined at different temperatures (60, 70, 80, and 90 °C) and pH levels (2, 4.5, and 6). The crocin degradation showed first order kinetic, and degradation rate constant (k) were significantly affected by pH and temperature (P < 0.05). A high temperature and low pH showed higher degradation (k) in crocin content. This study suggested that crocin from saffron stigmas should be preserved by spray drying encapsulation and should only be used as a natural food colorant in low or moderate acid food. [ABSTRACT FROM AUTHOR]

Stress-responsive dihydroxy flavonoids exhibit capability to inhibit the accretion of reactive oxygen species (ROS). The formation of these dihydroxy flavonols is catalyzed by flavonoid hydroxylases which are among the rate limiting enzymes of flavonoid biosynthesis pathway. Although flavonoid hydroxylases have been identified in several plant species but their role in abiotic stress is not explicitly documented. In the present study we report identification of all the flavonoid biosynthesis pathway genes of Crocus sativus and their expression profiling. We also report functional characterization of flavonoid 3′ hydroxylase (Cs F3′H) and attempt to explore its physiological role in vitro and in planta. The results indicated that Cs F3′H is 1608 bp long encoding 535 amino acids. Docking and enzyme kinetic studies revealed that Cs F3′H catalyzes hydroxylation of naringenin and dihydrokaempferol to eriodictoyl and dihydroquercetin respectively, but exhibits higher affinity for naringenin. Further, Cs F3′H showed comparatively higher expression in floral tissues particularly stigma and its expression was significantly enhanced in response to UV-B, dehydration and salinity stress indicative of its role in stress. The expression of Cs F3′H was associated with concomitant accumulation of eriodictoyl and dihydroquercetin. Transient overexpression of CsF3′H in Nicotiana benthamiana leads to the accumulation of substantial amounts of eriodictoyl and dihydroquercetin. Further, it was observed that transient expression of Cs F3′H conferred tolerance to UV-B and dehydration stress as was evident from higher chlorophyll and soluble sugar and lower MDA contents. Taken together, these results suggest that Cs F3′H confers tolerance to UV-B and dehydration in planta through synthesis of dihydroflavonols. [ABSTRACT FROM AUTHOR]

The impact of added saffron on the characteristics of yoghurt was evaluated during storage. The fat content was lower in the saffron yoghurt. All colour variables were significantly affected by saffron and storage. From the 15th day of storage, bacterial numbers in the saffron yoghurt were higher than those of the control yoghurt. Sensory analysis data suggested that colour, odour and texture impacted consistently on the overall acceptability of the saffron yoghurt. Saffron addition significantly increased polyphenol content and antioxidant activity, providing evidence that the enrichment of natural yoghurt with saffron yields an innovative fermented product useful for supplementing antioxidant dietary intake. [ABSTRACT FROM AUTHOR]

The medicinal uses of saffron, the dried stigmas of Crocus sativus L., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases. Crocus sativus is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on thimmune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. This review summarizes the protective roles of C. sativus and its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions. [ABSTRACT FROM AUTHOR]

Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans -crocin 4 and trans -crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer's Disease (AD), utilizing two AD neuronal cell culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 cells. When tested on neuronally differentiated SH-SY5Y-APP both trans -crocin 4 and trans -crocetin had significant effects against amyloidogenic pathways. Trans -crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans -crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of cellular AβPP. When tested on the neuronally differentiated PC12-htau cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans -crocin 4 and trans -crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD. [ABSTRACT FROM AUTHOR]

Introduction: The present study investigated for the first time, the antihyperglycemic effect of tepals and leaves of Crocus sativus in streptozotocin-induced diabetic rats. The effect of these by-products were compared with that of saffron stigma and glibenclamide. Methods: Hydroethanolic extracts (stigmas, tepals and leaves) and glibenclamide were administered orally in aqueous solution daily for 21 days. In the present study, 36 male rats were used. Six rats were used in each group. Group 1: normal control rats (N), received distilled water; group 2: diabetic control rats (D), received distilled water; group 3: treated diabetic rats (TPL), received tepal (TPL) extract; group 4: treated diabetic rats (STG), received stigma (STG) extract; group 5: treated diabetic rats (LF), received leaf (LF) extract and group 6: treated diabetic rats (GLB), received glibenclamide (GLB). Blood glucose, body weight, water intake, urine elimination, plasma triglycerides, cholesterol, urea, creatinine, aspartate amino transferase (AST) and alanine amino transferase (ALT) levels were evaluated. Results: The present data indicated that the tepals and stigmas extracts significantly prevented decreasing body weight and protected against elevation of water intake, urine elimination, blood glucose, plasma triglycerides, cholesterol, urea, creatinine, AST and ALT levels in treated diabetic rats as compared to untreated diabetic rats. Leaves extract significantly prevented decreasing body weight. It decreased water intake, blood glucose, plasma triglycerides, cholesterol, creatinine, AST and ALT. Conclusion: Based on our data, the oral administration of tepals, stigmas and leaves extract of Crocus sativus reduces blood glucose levels and improves control of diabetes complications. [ABSTRACT FROM AUTHOR]

The expression of biosynthesis controlling genes of crocin and safranal in saffron (Crocus sativus) can be influenced by ultrasonic waves. Sterilized saffron corms were cultured in a ½-MS medium supplemented by 2-4-D and BAP. Saffron callus cells were treated with ultrasonic waves in a cellular suspension culture under optimal growth conditions. The samples were collected at 24 and 72 hours after treatment in three replications. The secondary metabolites were measured by high-performance liquid chromatography and the gene expression was analysed by the real-time polymerase chain reaction. Results indicate that this elicitor can influence the expressions of genes CsBCH, CsLYC and CsGT-2; the ultrasonic waves acted as an effective mechanical stimulus to the suspension cultures. The analysis of variance of the ultrasonically produced amounts of safranal and crocin indicates that there is a significant difference between once- and twice-treated samples in that the amount of safranal was the highest within the samples taken from the twice-treated suspension culture at 72 h after the ultrasound treatment, and the crocin was maximised after 24 h passed the twice-applied ultrasound treatment. [ABSTRACT FROM AUTHOR]

Highlights • Lead is a risk factor for neurodegenerative disorders involving the dopaminergic and noradrenergic systems. • Pb toxicity alters dopaminergic, noradrenergic systems and locomotor behavior. • Pb could be involved in the neuro-physiopathology of Parkinson disease. • Crocus sativus repairs the Pb neurotoxicity of dopaminergic, noradrenergic systems and locomotor behavior. Abstract Lead (Pb) is a metal element released into the atmosphere and a major source of environmental contamination. The accumulation and concentration of this metal in a food web may lead to the intoxication of the body, more precisely, the nervous system (NS). In addition, Pb-exposure can cause structural and functional disruption of the NS. Studies have shown that Pb-exposure could be a risk factor in the development of Parkinson's disease (PD). The latter is related to dopaminergic deficiency that may be triggered by genetic and environmental factors such as Pb intoxication. In this study, we have evaluated, in one hand, the neurotoxic effect of Pb (25 mg / kg B.W i.p) for three consecutive days on dopaminergic system and locomotor performance in Merione shawi. In the other hand, the possible restorative potential of C. sativus (CS) (50 mg / kg BW) by oral gavage. The immunohistochemical approach has revealed that Pb-intoxicated Meriones show a significant increase of Tyrosine Hydroxylase (TH) levels within the Substantia Nigra compacta (SNc), Ventral Tegmental Area (VTA), Locus Coeruleus (LC), Dorsal Striatum (DS) and Medial Forebrain Bundle (MFB), unlike the control meriones, a group intoxicated and treated with Crocus sativus hydroethanolic extract (CSHEE) and treated group by CSHEE. Treatment with CSHEE, has shown a real potential to prevent all Pb-induced damages. In fact, restores the TH levels by 92%, 90%, 88%, 90% and 93% in SNc, VTA, LC, DS and MFB respectively, similarly, locomotor activity dysfunction in Pb-intoxicaed meriones was reinstated by 90%. In this study, we have revealed a new pharmacological potential of Crocus sativus that can be used as a neuroprotective product for neurodegenerative disorders, especially, which implying dopaminergic and noradrenergic injuries, like PD, trigged by heavy metals. [ABSTRACT FROM AUTHOR]

Abstract Generally, from the onset of dormancy to flowering, saffron farms are free of vegetation. Therefore, nutrients loss due to soil erosion, increased soil temperature and reduced land use efficiency are the most obvious problems of sole saffron cultivation, occurring over this period. Herein the intercropping advantage of saffron with watermelon or pumpkin and its effects on growth, yield and economic land equivalent ratio under limited irrigation were evaluated as a three-year field experiment (2014–2017) with a randomized complete blocks design arranged in factorial with three replicates. In this study, limited irrigation regimes on pumpkin and watermelon (14 and 28 days intervals) and cropping systems (saffron, pumpkin, watermelon, saffron + pumpkin and saffron + watermelon) were considered as the first and the second factors, respectively. Except for 2014, the individual effects of irrigation scheme and cropping systems on flower number and dried stigma yield were significant. In 2015, 2016, in comparison to saffron monoculture, intercropping significantly increased flower number and dried stigma yield. Moreover, in these years, increase in irrigation interval from 14 to 28 days significantly reduced average fruit weight in pumpkin and watermelon. The maximum land equivalent ratio and economic land equivalent ratio of saffron were found in saffron-pumpkin intercropping system with 14 days irrigation interval. Intercropping could positively affect saffron corms growth and N and P concentrations in the corms. In sum, considering the water shortage in arid and semi-arid regions, saffron-pumpkin or saffron-watermelon intercropping increases land efficiency and improves farmers' income during perennial life cycle of saffron. Highlights • Intercropping increased flower number and dried stigma yield in saffron. • Saffron yield was greater with pumpkin than with watermelon as a companion crop. • Increase in irrigation interval decreased economic land equivalent ratio in saffron. • N and P concentrations in the corms increased due to intercropping. • Reduction in irrigation interval increased large-sized daughter corms number. [ABSTRACT FROM AUTHOR]

Saffron (Crocus sativus L.) has been used both as a food additive for flavoring and coloring and in traditional medicine. Saffron extract and its main component crocin decrease the growth of several types of human cancer, including colorectal cancer in vitro. Numerous polyps develop in the small intestine in the Adenomatous polyposis coli (Apc) deficiency mice. ApcMin/+ mice are models for human familial adenomatous polyposis and human colon cancer patients. In this study, we examined the efficacy of saffron extract added to diet on reducing the polyp density in ApcMin/+ mice. ApcMin/+ mice were either given a placebo or saffron extract (0.1% and 0.5%) diet for 4 weeks. At 12 weeks of age, intestines were analyzed for polyp number in the small intestine. Our analysis confirmed that crocin (1), crocin-2 (2), and crocin-4 (4) are the major compounds in the saffron extract and the content of 1 in the tested saffron extract was 29.2%. Saffron extract decreased the number of intestinal polyps in a concentration-dependent manner in ApcMin/+ mice. Notably, the number of polyps in the distal small intestine of the mice fed with 0.5% saffron extract was significantly decreased compared with the placebo. These results indicate that saffron extract can reduce the polyp number in the ApcMin/+ mice. Abbreviations Used: FAP: Familial adenomatous polyposis; Apc: Adenomatous polyposis coli. [ABSTRACT FROM AUTHOR]

Saffron (Crocus sativus L.) is an important spice and medicinal plant that is cultivated in Asia, Europe, North Africa, and North America. Its morphological and biochemical parameters, such as the changes in the floral parts (six tepals, three stamens, three stigmata), biomass, and chlorophyll content, are primarily affected by environmental conditions. A polymerase chain reaction–rapid amplified polymorphic DNA (PCR‐RAPD) approach was used to analyze the extent of the polymorphisms between C. sativus genotypes grown in the Saudi climate. In this research study, the DNA fingerprints of the stigmata of C. sativus genotypes [K1 & K2 = C. sativus var. cashmerianus, C1 = C. sativus (nonmutant), T1 = mutant (T0‐2B), T2 = mutant (T1‐2B), T3 = mutant (T4‐2A)] were determined according to the floral parts, and a total of 10 decamer primers were used for PCR‐RAPD analysis. Only three pairs of arbitrary primers showed polymorphisms (33.3%–88.2%) in the total genomic DNA extracted from these genotypes. Jaccard's similarity index (JSI) ranged from 0.88 to 1.0. An unweighted pair group method with arithmetic mean (UPGMA) similarity and dendrogram matrix showed that two genotypes (T1‐2B and T4‐2A) were closely related to each other and to the strain CM‐cashmerianus, while the T0 of C. sativus genotype showed divergence. This study will provide a breakthrough in cultivating a mutant type of saffron, the most expensive spice worldwide in Saudi Arabia. [ABSTRACT FROM AUTHOR]

The dried stigmas of saffron constitute the world's costliest spice. Saffron has many therapeutic applications due to the presence of apocarotenoids. The latter are synthesized at different stages of development, and the biosynthetic pathway involves several genes encoding different enzymes. In order to understand the differential expression of various genes of the pathway, eight distinct developmental stages (S1-early to S8-late) were identified. The corms were assorted into three groups (I, II, and III) based on corm weight. Expression profiles of 12 carotenoid/apocarotenoid genes were studied. The expression of all genes was minimum/least in groups I and II corms during bud development. Lowest expression of carotenogenic genes (CsPSY, CsPDS, CsZDS, CsCRTISO, CsLYC-β1, CsLYC-ε, CsBCH2, and CsNCED) was observed during early stages (S1-S3) of corm growth (dormant period). In group III corms, increased expression of apocarotenoid genes (CsZCO, CsCCD2, CsUGT, and CsALDH) was observed during S4 to S8 stages (reproductive period, floral differentiation). Besides, expression profiles of genes in apical and axillary buds were also examined. Of all the genes studied, apocarotenoid biosynthesis genes (CsBCH2, CsZCO, CsCCD2, CsALDH, and CsUGT) were found to be upregulated in apical bud than in the axillary bud. The results indicated that interaction of phytohormones and sugars, mother corm reserves and the influence of internal and external factors may be contributing to the growth of saffron corm/bud. The study has laid a foundation for further research on the molecular mechanisms underlying bud dormancy/growth in saffron. [ABSTRACT FROM AUTHOR]

Saffron (Crocus sativus L.) is the most expensive spice in the world and is used in food, cosmetic and dyeing industries. Considering that the production of saffron is increasingly widespread in medium-small Italian farms as well as the scarceness of information and studies regarding the quality of the saffron produced in Italy, the principal aim of this study was to investigate the quality of Italian saffron. Qualitative analysis was conducted in accordance with ISO 3632 1,2:2010- 2011 considering 484 samples collected over four years (2015-2018). In particular, moisture content, aroma strength (safranal), colouring strength (crocin) and flavour strength (picrocrocin) were assessed for each sample, and whether spice quality varied according to the geographical area where the spice was produced was also investigated. Qualitative analysis showed that the majority (84-93%) of the samples analysed are of the first quality category, regardless of the year of production. Moisture content and colouring strength are the factors that influence the quality of the spice most. Principal component analysis showed that quality is not influenced by the geographical area where the spice was produced. Finally, some best agricultural practices to obtain a high quality saffron spice are reported. [ABSTRACT FROM AUTHOR]

Saffron, comprising of dried stigmas of the plant known as Crocus sativus, is one of the most important and scantly cultivated agricultural products. It has been used as a precious spice for the last at least 3500 years. Due to its numerous medicinal qualities and pharmacological applications, it is considered as a “golden condiment”, and its demand and consumptions has risen over a period of time. Although efforts are continuously being made to enhance the productivity in the traditional areas and promote the cultivation of saffron in the newer areas, there are several constraints hindering these efforts. Prevalence of corm rot is one such limiting factor which results in the reduction in saffron production and decline in the area under its cultivation. The disease not only reduces the yield substantially, but also adversely affects the production of daughter corms. Complete understanding and knowledge about the disease is still lacking due to the inadequate information about its etiology and epidemiology. Moreover, due to the non-availability of resistant genotypes and lack of improved cultural practices, presently no effective and sustainable management strategies are available. This review article gives an overall account of the history and impact of saffron corm rot, its present status, yield losses caused by it, dynamics of the pathogens associated with the disease, their survival and dispersal, factors influencing disease intensity, epidemiology and sustainable management strategies. As comprehensive information on the disease is presently not available, an attempt has been made to review the current knowledge regarding corm rot of saffron. The information about the disease discussed here can eventually be beneficial for the growers, students, researchers, plant protection organizations, development departments, extension workers, policy makers, government agencies and public organizations.

This study explores the prevalence, distribution, and codon usage bias of nematode species, primarily Heterodera glycines and Heterodera avenae , within saffron corms. Nematode analysis identified H. glycines and H. avenae as the predominant species. Geographical locations exhibited distinct cyst infestation levels, with H. avenae showing higher prevalence. The study reveals the preference of these nematodes for saffron corms, raising concerns for saffron production and suggesting the implementation of monitoring and management strategies. Additionally, the study analyzes the codon usage bias (CUB) of saffron and its associated nematode pathogens. Codon usage bias analysis revealed an AT bias in Crocus sativus and its pathogens. Codon Adaptation Index (CAI) values suggested pathogen adaptation to the host. Correlation analysis highlighted the interplay of nucleotide composition, mutational pressure, and natural selection in codon usage patterns. Amino acid frequency and codon context analyses provided insights into evolution and physiological functions. Furthermore, the study observed a mutual codon preference between the host and pathogens for certain amino acids, highlighting specific interactions at the molecular level. This study provides valuable information for understanding the molecular biology of plant-nematode interactions, and its findings can be useful for developing effective management strategies against these pests in saffron production and other crops such as crop rotation, use of resistant cultivars, and application of nematode-suppressive amendments. • Exploring the prevalence of nematode species, Heterodera glycines and Heterodera avenae, within saffron corms. • H. glycines and H. avenae are the dominant species found within saffron corms. • Analysis of codon usage bias in saffron and its associated nematode pathogens. • Mutual codon preferences between the host and the pathogens indicating co-adaptation. • Study's insights useful for developing effective management strategies against nematode pests. [ABSTRACT FROM AUTHOR]

Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC 50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC 50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant. [Display omitted] • The effect of C. sativus on inhaled PQ-induced lung injury were studied. • Treatment with C. sativus extract improved PQ induced lung injury. • The effect of the extract were similar to those of pioglitazone and dexamethasone. • There was a synergic effect between the extract with pioglitazone. • Possible PPARγ receptor-mediated effects of the plant was suggested. [ABSTRACT FROM AUTHOR]

Crocus sativus is an economically and pharmaceutically important crop. The dried stigmas of C. sativus flowers constitute saffron, the only commercial source of apocarotenoids like crocin, picrocrocin, and safranal. Some elite clones of C. sativus with higher crocin content were identified from plant populations over three years. Sequencing approach demonstrated that mutations are present in CstLycE. The C. sativus apocarotenoids are formed by cleavage of β-branch carotenoids. Cyclization of lycopene is the key branch point in carotenoid/apocarotenoid pathway. While lycopene β-cyclase converts lycopene into β-carotene, combined action of β and ε-cyclases forms α-carotene. Towards this, the mutant populations with critical mutations in CstLycE result in loss of function, and hence the metabolic flux was diverted towards β-branch. In-silico analysis and site-directed mutagenesis confirmed the critical nature of these mutations. To ascertain the role of CstLycE, transient over-expression and RNAi lines of CstLcyE in C. sativus were generated, and we observed enhanced β-branch carotenoid and apocarotenoid content in RNAi lines. The effect of CstLcyB and CstLcyE was compared, and CstLcyE RNAi lines had a more profound impact on apocarotenoid accumulation than CstLcyB over-expression lines. CstLcyE-RNAi plants also accumulated more abscisic acid and were more tolerant to abiotic stresses. • Natural mutations in CstLcyE lead to loss or reduced activity which diverts metabolic flux to the β-branch. • Reduced CstLcyE activity enhances crocin content. It also leads to abiotic stress tolerance. • It also leads to abiotic stress tolerance. [ABSTRACT FROM AUTHOR]

In the way of finding economic and tolerable plant to the arid and semi-arid climatic conditions and prevent desertification in these areas, this study aims to assess Agro-climatic suitability for producing Saffron in East-Azerbaijan province based on Geographic Information System (GIS) spatial analysis technique. For this goal, several criteria including soil conditions, climatological indicators, topography situation and agro-climatology criteria were taken into account of modeling process. For this to happen, standardization process was performed on criteria and weighting process was done by using of Analytic Hierarchy Process (AHP) approach. GIS based Multi-criteria Decision Analysis (MCDA) was employed for weighted overlapping of indicators and results were achieved based on GIS-MCDA method. Initial results indicated that East-Azerbaijan province has potential for cultivating of Saffron. Our research results indicated that about 42.7 percentage (1954416.9 ha) of this province has high suitability for Saffron producing. While, about 55.4 percentage (2537492.0 ha) of the study area has moderate suitability. In addition, about 1.8 percentage (84643.2 ha) of the study area represents low suitability. The results also indicated that, sum of sun hours and precipitation were supposed as important and limiting factors in the cultivation of this plant respectively. The founds of this research are great of importance for the purpose of regional planning in East-Azerbaijan province and also important in terms of developing methodology for precision agriculture which is one the main aspects of modern agriculture.

Saffron is cultivated for production of the saffron spice. Nevertheless, a huge amount of saffron by-products including corms, tepals and leaves with little or no commercial value are generated during the processing of the spice. This biomass contains bioactive compounds whose exploitation can increase the profitability and sustainability of this traditional crop. A significant amount of polyphenols, mainly glycosides of kaempferol, luteolin and quercetin, have been determined in tepals and leaves of saffron. Proliferation of Caco-2 cells was greatly inhibited by the tepal and leaf extracts (ED50 0.42 mg/ml), while the corm extract caused some signs of toxicity and completely abolished proliferation (ED50 0.05 mg/ml). To our knowledge, these are the first data reporting the inhibition of the proliferation of Caco-2 cells by extracts from tepals and leaves of saffron, and polyphenols could be responsible for this effect.

There is no ideal medication for a number of psychiatric and neurologic syndromes. In another words, some patients do not respond properly to synthetic medications or cannot tolerate the possible side effects. In this situation, alternative medicine and in particular herbal medicine can play an important role in the treatment. Of course, we should consider the principals of evidence based medicine in the application of alternative medicine. In this review, we focus on Crocus sativus, a Persian herb with history as long as the history of Iran. Recently a number of products from saffron have been presented for psychiatric and neurologic syndromes.

Background and aims: Crocus sativus is of medicinal plants possessing many beneficial effects in treatment of various disorders. This study aimed to overview the therapeutic effects of Crocus sativus on the basis of reviews and systematic reviews. Methods: Computerized search of review articles was performed using PubMed, Google Scholar, Scopus and Web of Science, Medline database from 1996 to 2015. Results: Searches identified 8 reviews and systematic reviews of therapeutic effects of Crocus sativus. Despite remarkable difference in interventions, and type of studies carried out on this plant (in vivo and in vitro), it seemed to have many therapeutic effects on the treatment of various types of diseases. In all the reviews, the objectives were similar, e.g. inhibition of growth of cancer cell lines, analgesic activity, improvement of health condition and treatment of some disease but the type of study (in vivo and in vitro) (animal studies: rat, mouse, guinipig, rabbit) and content was quite different. The most common effects of Crocus sativus were anti-carcinogenesis, tumoricidal, anti-depressant, antihypertensive, anticonvulsant, antitussive, anti-genototoxic and cytotoxic effects, anti-Alzheimer’s, antitussive, anxiolytic, aphrodisiac, antioxidant, anti-nociceptive, anti-inflammatory, relaxant activity, and effects on the gastrointestinal tract, on ocular blood flow and on retinal function, effect on coronary artery diseases, and hypnotic, and anesthetic effects. Conclusion: The results of various studies on Crocus sativus showed that it has a lot of therapeutic effects on the treatment of various types of diseases. However, to be able to use these results in our daily life, additional clinical trials with larger sample size and longer duration may be required to evaluate its toxicity and safety in each and every case of its therapeutic effects.

Cancer is the second leading cause of death globally with an estimated 9.6 million deaths in 2018 and a sustained rise in its incidence in both developing and developed countries. According to the WHO, about 1 in 6 deaths is due to cancer. Despite the emergence of many pioneer therapeutic options for patients with cancer, their efficacy is still time-limited and noncurative. Thus, continuous intensive screening for superior and safer drugs is still ongoing and has resulted in the detection of the anticancer properties of several phytochemicals. Among the spices, Crocus sativus L. (saffron) and its main constituents, crocin, crocetin, and safranal, have attracted the interest of the scientific community. Pharmacological experiments have established numerous beneficial properties for this brilliant reddish-orange dye derived from the flowers of a humble crocus family species. Studies in cultured human malignant cell lines and animal models have demonstrated the cancer prevention and antitumor activities of saffron and its main ingredients. This review provides an insight into the advances in research on the anticancer properties of saffron and its components, discussing preclinical data, clinical trials, and patents aiming to improve the pharmacological properties of saffron and its major ingredients.

Crocus sativus, a medicinally important herbaceous plant, has been traditionally used to cure coughs, colds, insomnia, cramps, asthma, and pain. Moreover, the therapeutic applications of saffron include its immunomodulatory and anticancer properties. The current experimental analysis was performed to explore the potential nutraceutical efficacy of corm, leaf, petal, and stigma of saffron ethanolic extracts as analgesic, anti-inflammatory, anticoagulant, and antidepressant using hot plate, carrageenan-induced paw edema, capillary tube and forced swim test, respectively in mice. The results indicated that among all the extracts, stigma ethanolic extract (SEE) represented maximum latency activity (72.85%) and edema inhibition (77.33%) followed by petal ethanolic extract (PEE) with latency activity and edema inhibition of 64.06 and 70.50%, respectively. Corm ethanolic extract (CEE) and leaf ethanolic extract (LEE) displayed mild analgesic activity of 22.40% and 29.07%, respectively. Additionally, LEE (53.29%) and CEE (47.47%) exhibited mild to moderate response against inflammation. The coagulation time of SEE (101.66 s) was almost equivalent to the standard drug, aspirin (101.66 s), suggesting a strong anticoagulant effect followed by PEE (86.5 s). LEE (66.83 s) represented moderate inhibitory effect on coagulation activity while CEE (42.83 s) showed neutral effect. Additionally, PEE and SEE also expressed itself as potential antidepressants with immobility time ≤76.66 s, while CEE (96.50 s) and LEE (106.83 s) indicated moderate to mild antidepressant efficacy. Based on the in vivo activities, saffron extract, particularly SEE and PEE, can be used as a potential nutraceutical and therapeutic agent due to its significant pharmacological activities.

Background: Oxidative stress and alteration of lipid profile due to obesity and overweight is a major risk factor for atherosclerotic plaque or coronary artery disease. Because of antioxidant and lipid lowering potential of saffron, this study investigated weight alteration, lipid profiles, and insulin resistance index in high-calorie diet rats treated with aqueous extract of saffron stigma and petal. Methods: Forty Sprague-Dawley male rats were randomly divided into 8 groups including healthy control, high-fat diet control, nicotinic acid treated, Anethum graveolens treated, and saffron stigma and petal treated groups. Rats received a high-calorie diet for 16 weeks. For treatment, aqueous extract of saffron stigma (40 and 80 mg/kg) and petal (50 and 100 mg/kg) was used once daily for 4 weeks. Afterward, lipid profile, oxidative stress status, and insulin and adiponectin levels were measured using desired kits. Results: There was a significant decrease in the mean weight of the groups receiving saffron stigma and petal compared to control group (P < 0.05). The increased level of insulin hormone in obese group was improved in treated groups especially in the case of saffron stigma. Also, the decreased level of adiponectin was recovered in treated groups. An improvement was seen in oxidative stress markers and lipid profiles in treated groups compared to obesity pair. Conclusions: In this study, a remarkable antioxidant and lipid lowering potential was detected for saffron stigma, which could improve insulin resistance in obese rats. Therapeutic and protective effect of saffron is mainly related to its richness in phenolic compounds. Saffron stigma compared with petal had more notable effect, which could and should be mentioned in pharmaceutical studies.

The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC−ESI-Q-TOF−MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

Background: In previous studies, extract of 3 herbs, celery, fenugreek and saffron was effective on primary dysmenorrhea. However, the health effects of saffron alone on primary dysmenorrhea have not been yet studied. The aim of this double blind, single center clinical trial is to examine the effects of saffron on primary dysmenorrhea pain in women aged 18-27 years old. Methods: One hundred eighty patients were randomly divided into three groups. Group 1 received saffron capsules three times per day for three days of menstrual period for three consecutive menstrual cycles. Group 2 received mefenamic acid, and group 3 has received identical placebo. Visual Analogue Scale (VAS) has been recorded at baseline and after each menstrual period. Results: In saffron group VAS was reduced from 6.8 to 3.6, 3.4, and 3 in 3 consecutive months. This effect was significantly greater than mefenamic acid and placebo (P:0.0001). Conclusions: It was found that the effect of saffron in reducing pain is more than mefenamic acid and far more than placebo.