Transcriptome analysis of apical meristem enriched bud samples for size dependent flowering commitment in Crocus sativus reveal role of sugar and auxin signalling.

BACKGROUND: Cultivation of Crocus sativus (saffron) faces challenges due to inconsistent flowering patterns and variations in yield. Flowering takes place in a graded way with smaller corms unable to produce flowers. Enhancing the productivity requires a comprehensive understanding of the underlying genetic mechanisms that govern this size-based flowering initiation and commitment. Therefore, samples enriched with non-flowering and flowering apical buds from small (< 6 g) and large (> 14 g) corms were sequenced. METHODS AND RESULTS: Apical bud enriched samples from small and large corms were collected immediately after dormancy break in July. RNA sequencing was performed using Illumina Novaseq 6000 to access the gene expression profiles associated with size dependent flowering. De novo transcriptome assembly and analysis using flowering committed buds from large corms at post-dormancy and their comparison with vegetative shoot primordia from small corms pointed out the major role of starch and sucrose metabolism, Auxin and ABA hormonal regulation. Many genes with known dual responses in flowering development and circadian rhythm like Flowering locus T and Cryptochrome 1 along with a transcript showing homology with small auxin upregulated RNA (SAUR) exhibited induced expression in flowering buds. Thorough prediction of Crocus sativus non-coding RNA repertoire has been carried out for the first time. Enolase was found to be acting as a major hub with protein-protein interaction analysis using Arabidopsis counterparts. CONCLUSION: Transcripts belong to key pathways including phenylpropanoid biosynthesis, hormone signaling and carbon metabolism were found significantly modulated. KEGG assessment and protein-protein interaction analysis confirm the expression data. Findings unravel the genetic determinants driving the size dependent flowering in Crocus sativus.

Therapeutic potential of saffron in brain disorders: From bench to bedside.

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.

Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

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.

Garlic Bulb Decay and Soft Rot Caused by the Cross-Kingdom Pathogen Burkholderia gladioli.

In 2021, two gram-negative bacterial strains were isolated from garlic (Allium sativum) bulbs showing decay and soft rot symptoms in Central Iran. The bacterial strains were aggressively pathogenic on cactus, garlic, gladiolus, onion, potato, and saffron plants and induced soft rot symptoms on carrot, cucumber, potato, and radish discs. Furthermore, they were pathogenic on sporophores of cultivated and wild mushrooms. Phylogenetic analyses revealed that the bacterial strains belong to Burkholderia gladioli. Garlic bulb rot caused by B. gladioli has rarely been reported in the literature. Historically, B. gladioli strains had been assigned to four pathovars, namely, B. gladioli pv. alliicola, B. gladioli pv. gladioli, B. gladioli pv. agaricicola, and B. gladioli pv. cocovenenans, infecting onion, Gladiolus sp., and mushrooms and poisoning foods, respectively. Multilocus (i.e., 16S rRNA, atpD, gyrB, and lepA genes) sequence-based phylogenetic investigations including reference strains of B. gladioli pathovars showed that the two garlic strains belong to phylogenomic clade 2 of the species, which includes the pathotype strain of B. gladioli pv. alliicola. Although the garlic strains were phylogenetically closely related to the B. gladioli pv. alliicola reference strains, they possessed pathogenicity characteristics that overlapped with three of the four historical pathovars, including the ability to rot onion (pv. alliicola), gladiolus (pv. gladioli), and mushrooms (pv. agaricicola). Furthermore, the pathotype of each pathovar could infect the hosts of other pathovars, undermining the utility of the pathovar concept in this species. Overall, using phenotypic pathovar-oriented assays to classify B. gladioli strains should be replaced by phylogenetic or phylogenomic analysis.

CstPIF4 Integrates Temperature and Circadian Signals and Interacts with CstMYB16 to Repress Anthocyanins in Crocus.

Crocus sativus has emerged as an important crop because it is the only commercial source of saffron that contains unique apocarotenoids. Saffron is composed of dried stigmas of Crocus flower and constitutes the most priced spice of the world. Crocus floral organs are dominated by different classes of metabolites. While stigmas are characterized by the presence of apocarotenoids, tepals are rich in flavonoids and anthocyanins. Therefore, an intricate regulatory network might play a role in allowing different compounds to dominate in different organs. Work so far done on Crocus is focussed on apocarotenoid metabolism and its regulation. There are no reports describing the regulation of flavonoids and anthocyanins in Crocus tepals. In this context, we identified an R2R3 transcription factor, CstMYB16, which resembles subgroup 4 (SG4) repressors of Arabidopsis. CstMYB16 is nuclear localized and acts as a repressor. Overexpression of CstMYB16 in Crocus downregulated anthocyanin biosynthesis. The C2/EAR motif was responsible for the repressor activity of CstMYB16. CstMYB16 binds to the promoter of the anthocyanin biosynthetic pathway gene (LDOX) and reduces its expression. CstMYB16 also physically interacts with CstPIF4, which in turn is regulated by temperature and circadian clock. Thus, CstPIF4 integrates these signals and forms a repressor complex with CstMYB16, which is involved in the negative regulation of anthocyanin biosynthesis in Crocus. Independent of CstPIF4, CstMYB16 also represses CstPAP1 expression, which is a component of the MYB-bHLH-WD40 (MBW) complex and positively controls anthocyanin biosynthesis. This is the first report on identifying and describing regulators of anthocyanin biosynthesis in Crocus.

Antimicrobial and anti-aflatoxigenic activities of nanoemulsions based on Achillea millefolium and Crocus sativus flower extracts as green promising agents for food preservatives.

BACKGROUND: Although the mechanism of action of nanoemulsion is still unclear, the modern use of nanoemulsions made from natural extracts as antimicrobial and anti-aflatoxigenic agents represents a potential food preservation and a safety target. METHODS: Two natural nanoemulsion extracts of Crocus sativus (the saffron flower) and Achillea millefolium (the yarrow flower) were produced in the current study using a low-energy method that included carboxymethylcellulose and Arabic gum. The synthesized nanoemulsion was fully identified by different analytical methods. Detection of the volatile content was completed using GC-MS analysis. The antioxidant potential, and phenolic compounds content were analyzed in the extractions. The synthesized nanoemulsions were screened for their antimicrobial potential in addition to their anti-aflatoxigenic activity. RESULTS: The droplet size of Saffron flowers was finer (121.64 ± 2.18 nm) than yarrow flowers (151.21 ± 1.12 nm). The Zeta potential measurements of the yarrow flower (-16.31 ± 2.54 mV) and the saffron flower (-18.55 ± 2.31 mV) both showed high stability, along with low PDI values (0.34-0.41). The nanoemulsion of yarrow flower revealed 51 compounds using gas chromatography-mass spectrometry (GCMS), with hexanal (16.25%), ß-Pinene (7.41%), ß-Myrcene (5.24%), D-Limonene (5.58%) and Caryophyllene (4.38%) being the most prevalent. Additionally, 31 compounds were detected in the saffron nanoemulsion, with D-limonene (4.89%), isophorone (12.29%), 4-oxy isophorone (8.19%), and safranal (44.84%) being the most abundant. Compared to the nanoemulsion of the yarrow flower, the saffron nanoemulsion had good antibacterial and antifungal activity. Saffron nanoemulsion inhibited total fungal growth by 69.64-71.90% in a simulated liquid medium and demonstrated the most significant decrease in aflatoxin production. Infected strawberry fruits coated with nanoemulsion extracts exhibited high antimicrobial activity in the form of saffron flower and yarrow flower extract nanoemulsions, which inhibited and/or controlled the growth of Aspergillus fungi. Due to this inhibition, the lag phase was noticeably prolonged, the cell load decreased, and the stability time increased. CONCLUSION: This study will contribute to expanding the theoretical research and utilization of nanoemulsions as green protective agents in agricultural and food industries for a promising protection from the invasion of some pathogenic bacteria and fungi.

Bioactivity and applications of saffron floral bio-residues (tepals): a natural by-product for the food, pharmaceutical, and cosmetic industries.

Saffron "Crocus sativus" is a plant of the Iridaceae family. Its therapeutic virtues have been known since antiquity; it is used in traditional medicine and culinary preparations. It is also known for its use in cosmetics because of its beneficial pharmacological activities for human skin. In particular, saffron tepals are the main by-product of saffron processing; they contain several bioactive compounds such as mineral agents, anthocyanins, monoterpenoids, carotenoids, flavonoids, and flavonols (kaempferol). This review aims to describe the different properties of saffron flower tepals, including their botanical characteristics, phytochemical composition, biological activities, and cosmetology and perfumery uses.

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.

Study on the interaction mechanism between Crocus sativus and Fusarium oxysporum based on dual RNA-seq.

KEY MESSAGE: The saffron phenylpropane synthesis pathway and Fusarium oxysporum cell wall-degrading enzymes play key roles in their early interactions. Saffron (Crocus sativus) is a highly important crop with diverse medicinal properties. F. oxysporum is a widely-distributed soil-borne fungus, causing the serious saffron rot disease. Currently, there is no effective management strategy to control this disease because of no resistant cultivars and limited information about the resistance and pathogenic mechanisms. In this study, we first characterized the infection process and physiological responses of saffron infected by F. oxysporum. The molecular mechanism of these infection interactions was revealed by dual RNA-seq analysis. On the 3rd day of infection, the hyphae completely entered, colonized and spread in the corm cells; while on the 6th day of infection, hyphae had appeared in the xylem cells, blocking these vessels. Transcriptome results indicate that within the host, phenylpropanoid metabolism, plant hormone signal transduction and plant pathogen interaction pathways were activated during infection. These pathways were conducive to the enhancement of cell wall, the occurrence of hypersensitivity, and the accumulation of various antibacterial proteins and phytoantitoxins. Meanwhile, in the fungus, many up-regulated genes were related to F. oxysporum cell wall degrading enzymes, toxin synthesis and pathogenicity gene, showing its strong pathogenicity. This study provides new ideas for the control of saffron corm rot, and also provides a theoretical basis for mining the key functional genes.

CstMYB1R1, a REVEILLE-8-like transcription factor, regulates diurnal clock-specific anthocyanin biosynthesis and response to abiotic stress in Crocus sativus L.

KEY MESSAGE: CstMYB1R1 acts as a positive regulator of Crocus anthocyanin biosynthesis and abiotic stress tolerance which was experimentally demonstrated through molecular analysis and over-expression studies in Crocus and Nicotiana. Regulatory mechanics of flavonoid/anthocyanin biosynthesis in Crocus floral tissues along the diurnal clock has not been studied to date. MYB proteins represent the most dominant, functionally diverse and versatile type of plant transcription factors which regulate key metabolic and physiological processes in planta. Transcriptome analysis revealed that MYB family is the most dominant transcription factor family in C. sativus. Considering this, a MYB-related REVEILLE-8 type transcription factor, CstMYB1R1, was explored for its possible role in regulating Crocus flavonoid and anthocyanin biosynthetic pathway. CstMYB1R1 was highly expressed in Crocus floral tissues, particularly tepals and its expression was shown to peak at dawn and dusk time points. Anthocyanin accumulation also peaked at dawn and dusk and was minimum at night. Moreover, the diurnal expression pattern of CstMYB1R1 was shown to highly correlate with Crocus ANS/LDOX gene expression among the late anthocyanin pathway genes. CstMYB1R1 was shown to be nuclear localized and transcriptionally active. CstMYB1R1 over-expression in Crocus tepals enhanced anthocyanin levels and upregulated transcripts of Crocus flavonoid and anthocyanin biosynthetic pathway genes. Yeast one hybrid (Y1H) and GUS reporter assay confirmed that CstMYB1R1 interacts with the promoter of Crocus LDOX gene to directly regulate its transcription. In addition, the expression of CstMYB1R1 in Nicotiana plants significantly enhanced flavonoid and anthocyanin levels and improved their abiotic stress tolerance. The present study, thus, confirmed positive role of CstMYB1R1 in regulating Crocus anthocyanin biosynthetic pathway in a diurnal clock-specific fashion together with its involvement in the regulation of abiotic stress response.

The anti-echinococcal activity of crocin in mice experimentally infected with Echinococcus granulosus.

Herbal preparations have good medicinal value for potential use as therapeutic agents in cystic echinococcosis. The efficiency of crocin in the case of cystic echinococcosis was investigated, and compared with that of albendazole, one of the few licensed anti-echinococcosis drugs that served as a positive control. Five months after infecting BALB/C mice with E. granulosus sensu lato the experimental group was divided into 7 subgroups containing 10 animals each: 1- Crocin 80 (80 mg/kg), 2- Crocin 40 (40 mg/kg), 3- Crocin 10 (10 mg/kg), 4- Albendazole (200 mg/kg), 5- Crocin 10 (10 mg/kg) +Albendazole (100 mg/kg), 6- Crocin 20 (20 mg/kg) +Albendazole (50 mg/kg), 7- the control (infected and untreated). After two weeks of daily treatment, significant reductions of cysts' weights, sizes, and total numbers concerning the control group were achieved by treatment with crocin 80, crocin 40, crocin 10, crocin 10 + ABZ100, crocin 20+ ABZ50 and ABZ200 (p < 0.05). Moreover, there was no difference concentrations of crocin and those treated with albendazole,. The concentration of bilirubin was higher in the control group than all treated groups with crocin, significantly. However, the ALT activity showeda significant decrease in the crocin 10 group, compared to the crocin 80, crocin 40, crocin 10 + ABZ100, crocin 20 + ABZ50, control groups (p < 0.05). Based on our results, the administration of crocin used at 10 mg/kg concentrations seems a hopeful applicant for the treatment of cystic echinococcosis.

Saffron (Crocus sativus) and its constituents for pain management: A review of current evidence.

Pain can become a chronic and deliberating experience with a significant burden. In preclinical and clinical studies, Saffron (Crocus sativus L.) has shown analgesic activities. Considering the unsatisfactory results of current therapeutic management for chronic pain conditions, we aimed to review saffron's analgesic activity and underlying mechanisms. Saffron showed antinociceptive activities in formalin-, carrageenan-, and capsaicin-induced experimental pain models. Saffron analgesic activities affected several targets, including ion channels of nociceptors; the adrenergic system and central histaminic system; inhibition of inflammatory pathways, apoptotic pathways, and oxidative stress; regulation of NO pathway, and the endocannabinoid system. Clinical studies showed analgesia of Saffron in rheumatoid arthritis, after-pain following childbirth, dysmenorrhea, and fibromyalgia. Our literature review showed that saffron can be beneficial as an adjunct therapy to commonly used analgesics in practice, particularly in chronic pain conditions.

Insights on the Hypoglycemic Potential of Crocus sativus Tepal Polyphenols: An In Vitro and In Silico Study.

Post-prandial hyperglycemia typical of diabetes mellitus could be alleviated using plant-derived compounds such as polyphenols, which could influence the activities of enzymes involved in carbohydrate digestion and of intestinal glucose transporters. Here, we report on the potential anti-hyperglycemic effect of Crocus sativus tepals compared to stigmas, within the framework of valorizing these by-products of the saffron industry, since the anti-diabetic properties of saffron are well-known, but not those of its tepals. In vitro assays showed that tepal extracts (TE) had a greater inhibitory action than stigma extracts (SE) on α-amylase activity (IC50: TE = 0.60 ± 0.09 mg/mL; SE = 1.10 ± 0.08 mg/mL; acarbose = 0.051 ± 0.07) and on glucose absorption in Caco-2 differentiated cells (TE = 1.20 ± 0.02 mg/mL; SE = 2.30 ± 0.02 mg/mL; phlorizin = 0.23 ± 0.01). Virtual screening performed with principal compounds from stigma and tepals of C. sativus and human pancreatic α-amylase, glucose transporter 2 (GLUT2) and sodium glucose co-transporter-1 (SGLT1) were validated via molecular docking, e.g., for human pancreatic α-amylase, epicatechin 3-o-gallate and catechin-3-o-gallate were the best scored ligands from tepals (-9.5 kcal/mol and -9.4 kcal/mol, respectively), while sesamin and episesamin were the best scored ones from stigmas (-10.1 kcal/mol). Overall, the results point to the potential of C. sativus tepal extracts in the prevention/management of diabetes, likely due to the rich pool of phytocompounds characterized using high-resolution mass spectrometry, some of which are capable of binding and interacting with proteins involved in starch digestion and intestinal glucose transport.

Combination of Caffeic Acid Phenethyl Ester and Crocin Realign Potential Molecular Markers in U87-MG Glioma Cells.

Background: Glial tumors are the most common primary malignant central nervous system tumors. They are hard to treat, not only because of the deregulation in multiple pathways but also because they are not contained in a well-defined mass with clear borders. The use of a single therapeutic agent to target gliomas has yielded unsatisfactory results. Objective: A combination of molecules targeting multiple pathways may prove to be a better alternative. Methods: The effect of caffeic acid phenethyl ester and crocin on the proliferation and death of U87-MG cells over a concentration range was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. A colony formation assay was used to measure the effect of caffeic acid phenethyl ester and crocin on contact inhibition and anchorage independence ability of U87-MG cells. Furthermore, apoptosis in U87-MG cells was analyzed by propidium iodide assay. Real-time polymerase chain reaction and Western blotting were performed to determine the expression level of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen. Results: Caffeic acid phenethyl ester and crocin when used in combination present an anticancer potential for glioma. These molecules, in combination, inhibit proliferation and induce apoptosis in U87-MG glioma cells. Our results provide evidence that combination treatment realigns the expression paradigm of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen in cotreated U87-MG cells. Conclusions: The combination of caffeic acid phenethyl ester and crocin led to inhibition in glioma cell proliferation and might prove to be an effective adjunct to the therapies in vogue.

Saffron, as an adjunct therapy, contributes to relieve depression symptoms: An umbrella meta-analysis.

BACKGROUND: Saffron is a traditional herbal medicine that has been used to treat various ailments such as depressive mood. However, the findings of several meta-analyses regarding anti-depressive properties of saffron (Crocus sativus L.) are controversial. The current umbrella meta-analysis was carried out to determine the magnitude and direction of saffron administration on depression. METHODS: Relevant studies were searched in international databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to June 2021. Meta-analysis studies investigating the effects of saffron on depression were considered to include in the study. Random-effects model was used to perform the meta-analysis. Additional analyses including subgroup and sensitivity analyses were carried out. RESULTS: Overall, 7 meta-analyses were included in the study. The results demonstrated that the consumption of saffron resulted in a significant reduction in BDI scores (ES: -3.87; 95% CI: -5.27, -2.46). However, saffron did not change the HAMD scores (ES: -2.10; 95% CI: -5.05, 0.86, p = 0.164) and mixed scores (HAM-D/BDI/DASS) (ES: 0.02; 95% CI: -0.39, 0.43,p = 0.941). CONCLUSION: Present umbrella meta-analysis demonstrated that saffron intake might contribute to alleviation of depression disorder, however, it cannot be considered as a single therapeutic approach to treat depression.

Nutritional and health beneficial properties of saffron (Crocus sativus L): a comprehensive review.

Saffron (Crocus sativus L., family Iridaceae) is used traditionally for medicinal purpose in Chinese, Ayurvedic, Persian and Unani medicines. The bioactive constituents such as apocarotenoids, monoterpenoids, flavonoids, phenolic acids and phytosterols are widely investigated in experimental and clinical studies for a wide range of therapeutic effects, especially on the nervous system. Some of the active constituents of saffron have high bioavailability and bioaccessibility and ability to pass the blood-brain barrier. Multiple preclinical and clinical studies have supported neuroprotective, anxiolytic, antidepressant, learning and memory-enhancing effect of saffron and its bioactive constituents (safranal, crocin, and picrocrocin). Thus, this plant and its active compounds could be a beneficial medicinal food ingredient in the formation of drugs targeting nervous system disorders. This review focuses on phytochemistry, bioaccessibility, bioavailability, and bioactivity of phytochemicals in saffron. Furthermore, the therapeutic effect of saffron against different nervous system disorders has also been discussed in detail.

The effects of saffron (Crocus sativus L.) in conjunction with concurrent training on body composition, glycaemic status, and inflammatory markers in obese men with type 2 diabetes mellitus: A randomized double-blind clinical trial.

AIMS: Chronic inflammation is one of the major challenges in the management of obesity and type 2 diabetes mellitus (T2DM). Our primary aim was to assess the anti-inflammatory effects of Saffron (Crocus sativus L.) supplementation and concurrent training in obese men with T2DM. METHODS: Sixty obese men with T2DM (age = 39 ± 5 years; body mass = 93.9 ± 6 kg) were randomly assigned to four groups; concurrent training + placebo (CT; n = 15), saffron supplementation (S; n = 15), concurrent training + saffron supplementation (CTS; n = 15), or control (CON; n = 15). The participants in the CT group performed concurrent training (resistance + aerobic) three times per week for 12 weeks and received daily one pill of placebo (maltodextrin); the participants in the S group supplemented with one pill of 100 mg of saffron daily, and the participants in the CTS group participated in both saffron and training intervention while CON group continued regular lifestyle (no training and no supplementation). Inflammatory markers, body composition (evaluated by a multi-frequency bioelectrical impedance device; Jawon X-Contact 356), and metabolic profile were evaluated before and after interventions. RESULTS: All three interventions significantly (P < .05) decreased TNF-α (CT = -4.22, S = -1.91, CTS = -9.69 pg/mL), hs-CRP (CT = -0.13, S = -0.1, CTS = -0.32 ng/mL), IL-6 (CT = -6.84, S = -6.36, CTS = -13.55 pg/mL), IL-1ß (CT = -8.85, S = -6.46, CTS = -19.8 pg/mL), FBG (CT = -6.97, S = -2.45, CTS = -13.86 mg/dL), insulin (CT = -0.13, S = -0.03, CTS = -0.21 mU/L), HOMA-IR (CT = -0.12, S = -0.04, CTS = -0.21), HbA1c (CT = -0.17, S = -0.11, CTS = -0.26%), and increased IL-10 (CT = 1.09, S = 0.53, CTS = 2.27 pg/mL) concentrations. There was a positive correlation between changes in BFP with hs-CRP, IL-6, IL-1ß and TNF-α, and IL-10 concentrations across the intervention groups. Additionally, significant differences were observed between the changes for all variables in the CTS group compared to CT, S and CON groups (P < .05). CONCLUSION: It seems that an interaction of saffron supplementation and concurrent training has more efficient effects on anti-inflammatory status compared to saffron supplementation or concurrent training alone.

Understanding saffron biology using omics- and bioinformatics tools: stepping towards a better Crocus phenome.

Saffron is a unique plant in many aspects, and its cellular processes are regulated at multiple levels. The genetic makeup in the form of eight chromosome triplets (2n = 3x = 24) with a haploid genetic content (genome size) of 3.45 Gbp is decoded into different types of RNA by transcription. The RNA then translates into peptides and functional proteins, sometimes involving post-translational modifications too. The interactions of the genome, transcriptome, proteome and other regulatory molecules ultimately result in the complex set of primary and secondary metabolites of saffron metabolome. These complex interactions manifest in the form of a set of traits 'phenome' peculiar to saffron. The phenome responds to the environmental changes occurring in and around saffron and modify its response in respect of growth, development, disease response, stigma quality, apocarotenoid biosynthesis, and other processes. Understanding these complex relations between different yet interconnected biological activities is quite challenging in saffron where classical genetics has a very limited role owing to its sterility, and the absence of a whole-genome sequence. Omics-based technologies are immensely helpful in overcoming these limitations and developing a better understanding of saffron biology. In addition to creating a comprehensive picture of the molecular mechanisms involved in apocarotenoid synthesis, stigma biogenesis, corm activity, and flower development, omics-technologies will ultimately lead to the engineering of saffron plants with improved phenome.

The therapeutic potential of Crocus sativus Linn.: A comprehensive narrative review of clinical trials.

Crocus sativus Linn. (Saffron) is valued worldwide for its potential use in the management of various degenerative disorders, including cardiovascular diseases (CVDs), diabetes, cancer, metabolic syndrome (MetS), neurodegenerative diseases, immune disorders, and sexual dysfunction. Previous reports, based on clinical trials, suggest that crocetin, crocin, picrocrocin, and safranal are the main bioactive components of saffron with antioxidant, anti-inflammatory, and anti-apoptotic effects. In this comprehensive narrative review, we studied the recent clinical trials, investigating the medicinal applications of saffron and/or its components. The present results can provide important insights into the potential of saffron in preventing and treating different disorders, with a special focus on the underlying cellular and molecular mechanisms. However, further high-quality studies are needed to firmly establish the clinical efficacy of saffron in treating some degenerative diseases.

Crocin molecular signaling pathways at a glance: A comprehensive review.

Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic-AMP response element-binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll-like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP-activated protein kinase, mitogen-activated protein kinases (MAPK), and peroxisome proliferator-activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/ß-catenin, and Janus kinases-signal transducer and activator of transcription suppression. Also, the nuclear factor-erythroid factor 2-related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.