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Objective(s): Alzheimer’s disease (AD) is a neurodegenerative disease that results in the gradual breakdown of brain tissue, causing the deterioration of intellectual function and ability. Crocin is a saffron carotenoid compound proven to have excellent neuroprotective and anti-inflammation properties, although it has some limitations such as low stability and bioavailability. Therefore, in the current research, we tried to improve these limitations by using nanotechnology and chitosan as the carrier. Our study examined the therapeutic effects of crocin nano-chitosan-coated compound and compared it with intact crocin in lower dosages than other studies in AD rat models. Materials and Methods: Encapsulating crocin into chitosan nanoparticles was done through a modified technique to improve its limitations. The AD rat model was induced by bilaterally injecting beta-amyloid (Aβ) peptide into the frontal lobe using a stereotaxic device. To evaluate memory, we conducted the Barnes maze test, and to evaluate anxiety, we used the elevated plus maze test. Also, histological tests were conducted to evaluate neuronal damage in each group. Results: Crocin nano-chitosan-coated administration significantly improved specific memory indicators compared to the Aβ and other treated groups. A significant decrease in anxiety indicators was detected compared to the Aβ and other treated groups. Finally, the results of hippocampus staining indicated a meaningful difference between the Aβ group and other treated groups, compared to the crocin nano-chitosan-coated group. Conclusion: Treatment with low dosages of crocin in the nano-coated form exhibited great efficacy in reducing AD’s adverse effects compared to the same dosage of intact crocin. [ABSTRACT FROM AUTHOR]

Objective(s): Adult neurogenesis, the process of generating new neurons, continues throughout life. Unfortunately, this process is insufficient in pathological conditions and needs to be promoted. Crocin, the active component of saffron, affects neurogenesis in vivo and in vitro. We aimed to investigate the enhancing effects of crocin on the neurogenesis of adipose-derived mesenchymal stem cells in the presence of retinoic acid, as well as the molecular pathways involved. Materials and Methods: Differentiation capacities and stemness potential of harvested ADSCs were evaluated by differentiating into osteocytes and adipocytes, and expression of mesenchymal CD markers by flow cytometry. The optimum dose of crocin was assessed with an MTT assay. Crocin, retinoic acid, CREB/BDNF, and Notch inhibitors and their combination were added to the culture medium. Jag1, Hes1, Notch, and BDNF gene expression were analyzed by RT-PCR on days 7, 14, and 21, while CREB, DCX, SOX2, and NeuN expression were analyzed by immunofluorescence. Results: Expression of mesenchymal CD markers as well as adipogenic and osteogenic differentiation confirmed the origin and properties of ADSCs. The optimal dose of crocin was 1 mM. Crocin significantly (P<0.05) increased, while inhibitors (DATP&Naphthol) significantly (P<0.05) decreased Jag1, Hes1, Notch, and BDNF expression. Immunofluorescent assessments showed that expression of DCX, BDNF, NeuN, and Sox2 proteins increased significantly (P<0.05) after crocin administration and decreased significantly (P<0.05) after inhibitor administration. Conclusion: Crocin can be used as an enhancer for neural differentiation of MSCs in vitro in the presence of retinoic acid. The mechanism is proposed through Notch and CREB/BDNF signaling pathways. [ABSTRACT FROM AUTHOR]

Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy. [ABSTRACT FROM AUTHOR]

Saffron cultivation is important in global agriculture and is mainly flourishing in Mediterranean climates. Although it originated in Asia Minor, it is widely grown in regions such as Iran, India, Spain, Morocco, Greece, and Italy. Labour-intensive harvesting, mainly by hand, characterises its production and offers substantial employment opportunities in cultivating areas. However, traditional saffron-producing countries such as Spain, Italy, and Greece have witnessed declining production due to labour demands and competition from low-wage countries. Mechanization remains unfeasible due to the delicate nature of the plant. To revitalise saffron cultivation, efforts have been focused on reducing labour costs, improving productivity, and improving quality through innovative techniques, such as soilless crops. In this study, the productivity and quality of saffron was evaluated in a soilless culture and three fertigation doses were evaluated: a control, consisting of Sonneveld and Voogt's standard nutrient solution, and two treatments with two supplemented solutions, 30% K and 30% Ca. The results indicated that the solution with 30% K obtained higher corm productivity, as well as better quality saffron, as all the products of this treatment were included in Category I according to the ISO 3632 standard, while the quality of saffron grown with the control solution was lower. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of clinical syndromes that is closely associated with an elevated risk of developing atherosclerotic cardiovascular disease. In a series of animal experiments and clinical trials, crocus sativus and its component crocin have demonstrated promising hypoglycemic effects. However, there is currently insufficient evidence regarding their impact on cardiometabolic parameters. Our study aimed to assess the impact of Crocus sativus and crocin on glycemic control in individuals with metabolic syndrome and associated disorders, as well as their potential effects on improving cardiometabolic parameters. We searched Cochrane Library, PubMed, Embase, and Web of Science databases to ascertain the pertinent randomized controlled trials (RCTs) until December 30, 2023. Q-test and I2 statistics were utilized to evaluate heterogeneity among the included studies. Data were merged using a random-effects model and presented as (WMD) with a 95% confidence interval (CI). The current comprehensive review and meta-analysis, encompassing 13 RCTs involving a total of 840 patients diagnosed with metabolic syndrome and associated disorders, demonstrates that Crocus sativus was superior to placebo on Hemoglobin A1c(HbA1c) (WMD: -0.31;95% CI [-0.44,-0.19]. P = 0.002) and systolic blood pressure(SBP) (WMD:-7.49;95% CI [-11.67,-3.30]. P = 0.99) respectively. Moreover, Crocus sativus improved fasting blood glucose (FBG) (WMD:-7.25;95% CI [-11.82, -2.57]. P = 0.002) when used crocin and on other chronic diseases. Crocus sativus reduced the total cholesterol (TC) among the metabolic syndromepatients (WMD:-13.64;95%CI [-26.26, -1.03]. P = 0.03). We demonstrated that Crocus sativus exerts beneficial effects on glycemic control and cardiometabolic parameters in individuals with metabolic syndrome and related disorders. [ABSTRACT FROM AUTHOR]

Objective: Mobile devices are sources of electromagnetic fields (EMFs) that cause increasing concern among scientists about human health, especially with the long-term use of mobile phones. With regard to this issue, the potential adverse health effects, particularly on brain function have raised public concern. There is considerable evidence that natural compounds have neuroprotective effects due to their antioxidant and anti-inflammatory properties. Growing evidence suggests that crocin as a natural bioactive compound can be considered a potential therapeutic agent against various neurologic disorders. Therefore, the present study investigated the effects of crocin on the cerebellum after exposure to EMF. Materials and Methods: Twenty-four Male Balb/c mice were divided into control group, EMF group (2100 MHZ), EMF +Crocin group (2100 MHZ+50 mg/kg), and crocin group (50 mg/kg). The animals in the EMF and EMF+Crocin groups were exposed continuously for 30 days to an EMF 120 min/day. After 30 days, cerebellar cortex was evaluated by histomorphometric and immunohistochemical methods. Results: The results showed that 30 days of exposure to EMF had no significant effect on Purkinje cell size. However, EMF reduced significantly the diameter of astrocytes and increased Glial fibrillary acidic protein (GFAP) expression compared to the controls (p<0.05). Our findings also indicated that crocin treatment could improve the diameter of astrocytes and normalize GFAP expression (p<0.05). Conclusion: This study concluded that 2100-MHz EMF caused adverse eff ects on the cerebellum through astrocyte damage and crocin could partially reverse the EMF-related adverse effects. [ABSTRACT FROM AUTHOR]

Background: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. Methods: AD mice were set up by injecting Aβ25‐35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open‐field test, Y‐maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL‐1β, IL‐6, and TNF‐α), and PI3K/AKT signaling‐related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real‐time polymerase chain reaction (qRT‐PCR) experiments, respectively. Results: Crocin attenuated Aβ25‐35‐induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT‐PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aβ25‐35‐induced mice. Conclusion: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice. [ABSTRACT FROM AUTHOR]

Objective(s): Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro. Materials and Methods: BM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively. Results: Our findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7 µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group. Conclusion: Our results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area. [ABSTRACT FROM AUTHOR]

We investigated the role of miR-99a in regulating depressant activity by administering crocin in an animal model of chronic unpredictable mild stress (CUMS). A CUMS rat model was built and crocin was intraperitoneally injected to examine its role in depression-like behaviors. Depression-like behaviors were analyzed using an open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and elevated maze test (EPM). Representative depressant activity occurred in CUMS rats. The SPT/OFT/EPM/FST results also indicated that the administration of crocin could reduce depression-like activity in CUMS rats. Postsynaptic density protein 95 (PSD-95), SYN, P-TrkB, BDNF protein expression was remarkably downregulated in the hippocampal formation of CUMS rats but was recovered after treatment with crocin. In addition, crocin injection increased norepinephrine (NE)/ dopamine (DA)/ serotonin (5-HT) levels in the hippocampus of CUMS rats. miR-99a expression in the hippocampal formation of CUMS rats was remarkably lower than that in the control group; crocin administration increased hippocampal miR-99a levels. In addition, the upregulation of miR-99a in the hippocampus of CUMS rats resulted in a phenotype similar to that of the crocin injection group, whereas miR-99a downregulation in crocin-injected CUMS rats counteracted the effect of crocin on depression-like behaviors. Moreover, FKBP51 was identified as a direct target of miR-99a, which inhibits downstream FKBP51 in primary hippocampal neurons. Crocin exerts anti-depressant effects in hippocampal dysfunction by promoting miR-99a and activating the TrkB/BDNF signaling pathway in the hippocampal formation of CUMS rats. [ABSTRACT FROM AUTHOR]

The synthesis of magnetic nanoparticles enclosed in zeolitic imidazolate frameworks (MNPs@ZIF-8) was successful carried out at ambient temperature and atmospheric pressure. The synthesis procedure was selected because it is uncomplicated and does not call for the use of any sophisticated pieces of apparatus throughout its execution. The Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) images were investigated to characterize the materials. The analysis of the data allowed MNPs@ZIF-8 to evolve into a highly crystalline phase with particles ranging in size from 50 to 100 nanometers. This was made feasible by the fact that the phase could be created. It was explored whether or not MNPs@ZIF-8 was effective as a nanocarrier for the delivery of natural medicines like crocin. It was demonstrated to be very biocompatible and had an IC50 value of > 1000 μg/mL, which is the concentration at which half of the maximum inhibitory effect is produced. The IC50 value for crocin-loaded MNPs-ZIF-8 was 419 ± 0 μg/mL, which was roughly half of the IC50 value for pure crocin, which was 716 ± 160 μg/mL. [ABSTRACT FROM AUTHOR]

Objective(s): Diabetic nephropathy (DN) is the main cause of end-stage renal disease, but the current treatment is not satisfactory. Crocin is a major bioactive compound of saffron with antioxidant and anti-endoplasmic reticulum stress (ERS) abilities used to treat diabetes. This study specifically investigated whether crocin has a regulatory role in renal injury in DN. Materials and Methods: The experiment was divided into control, (db/m mice), model (db/db mice), and experimental groups (db/db mice were intraperitoneally injected with 40 mg/kg crocin). Renal function-related indicators (Scr, BUN, FBG, UP, TG, TC, ALT, and AST) and oxidative stress-related indicators (ROS, MDA, GSH, SOD, and CAT) were assessed. The pathological changes of renal tissues were confirmed by HE, Masson, PAS, and TUNEL staining. The levels of ERS-related proteins (GRP78 and CHOP), apoptosis-related proteins, and PI3K/AKT and Nrf2 pathways-related proteins in renal tissue were detected. Results: In db/db mice, renal function-related indicators, apoptotic cells of renal tissues, the contents of ROS and MDA as well as the expressions of CHOP, GRP78, and Bax were increased, the degree of renal tissue damage was aggravated, while the contents of GSH, SOD, and CAT, as well as the protein levels of Nrf2, PARP, anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) were decreased compared to the db/m mice. However, crocin treatment reversed the above-mentioned situation. The expressions of the PI3K/AKT and Nrf2 pathways-related proteins were also activated by crocin. Conclusion: Crocin inhibited oxidative stress and ERS-induced kidney injury in db/db mice by activating the PI3K/AKT and Nrf2 pathways. [ABSTRACT FROM AUTHOR]

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders. [ABSTRACT FROM AUTHOR]

Objectives: Crocin is a major class of medicinal components in saffron. This study aimed to determine whether crocin directly promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in vitro and in vivo. Materials and Methods: CCK8 cell proliferation assay, reverse transcription quantitative polymerase chain reaction (RT–qPCR), Western blot analysis and Alizarin Red staining were performed in PDLSCs using crocin as a stimulant. DKK1 was used to selectively inhibit Wnt/β‐catenin signaling, and Western blotting was performed to investigate the underlying mechanism. The PDLSCs were mixed with calcium phosphate cement and implanted into nude mice subcutaneously to study the effect of crocin on PDLSC osteogenic differentiation in vivo. Results: The CCK‐8 assay showed that crocin did not promote the proliferation of PDLSCs. Treatment with 400 μM crocin significantly promoted PDLSC mRNA levels of ALP, COL1 and OCN; RUNX2 and BMP2 protein expression; mineralized nodule formation in vitro and in vivo; and ALP activity in tissues in vivo. In addition, crocin significantly promoted the phosphorylation of β‐catenin and cyclin D1. DKK1 inhibits Wnt/β‐catenin activation and partially reverses crocin‐mediated promotion of PDLSC osteogenic differentiation. Conclusion: Crocin may contribute to the regeneration of periodontal bone tissue. [ABSTRACT FROM AUTHOR]

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin–spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry. [ABSTRACT FROM AUTHOR]

To investigate the role of Crocin on proliferation, fibrosis, and migration of orbital fibroblasts, as well as the possible signaling pathway. Immunofluorescence assay was performed to detect the expression of fibroblast marker proteins vimentin cytokeratin, desmin, and S-100. The quantity of 5‑ethynyl‑2′‑deoxyuridine-positive cells in orbital fibroblast was analyzed. Quantitative real-time PCR and western blots were performed to evaluate the expression level of fibrosis-related marker including alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1, and fibronectin. Scratch wound assays were performed to assess wound widths of orbital fibroblast. The expression and phosphorylation of extracellular signal-regulated kinase/signal transducer and activator of transcription 3 were evaluated using western blots. The phosphorylation of smad2 and smad3 was evaluated using immunofluorescence assay. Crocin treatment reduced 5‑ethynyl‑2′‑deoxyuridine-positive cells, indicating inhibitory effect on orbital fibroblast proliferation. The expression levels of alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1 and fibronectin were declined in Crocin treatment. Delayed wound closures were observed in Crocin treatment. Furthermore, Crocin did not affect the expression of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, but weakened extracellular signal-regulated kinase and signal transducer and activator of transcription 3 phosphorylation in orbital fibroblast. The phosphorylation of smad2 and smad3 was attenuated by Crocin as well. In conclusion, Crocin inhibits the phosphorylation of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, contributing to the inhibitory effect on proliferation, fibrosis, and migration of orbital fibroblast, suggesting that Crocin has potential to be a novel therapeutic candidate for thyroid-associated ophthalmopathy treatment. [ABSTRACT FROM AUTHOR]

Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200–250 g were used (6–7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity. [ABSTRACT FROM AUTHOR]

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX) is one of the first‐line chemotherapeutic agents for treating breast cancer. However, PTX resistance remains a major hurdle in breast cancer therapy. Crocin, the main chemical constituent of saffron, shows anti‐cancer activity against various types of cancer. However, the effect of crocin on the resistance of PTX in breast cancer is still unknown. CCK‐8 and TUNEL assays were employed to detect cell viability and apoptosis, respectively. The targets of crocin were predicted using HERB database and the targets associated with breast cancer were acquired using GEPIA database. The Venn diagram was utilized to identify the common targets between crocin and breast cancer. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) expression was detected by qRT‐PCR and western blot analysis. The correlation between BIRC5 expression and survival was analyzed by Kaplan–Meier plotter and PrognoScan databases. Our data suggested that crocin aggravated PTX‐induced decrease of viability and increase of apoptosis in MCF‐7 and MCF‐7/PTX cells. BIRC5 was identified as the target of crocin against breast cancer. Crocin inhibited BIRC5 expression in MCF‐7 and MCF‐7/PTX cells. BIRC5 is overexpressed in breast cancer tissues, as well as PTX‐sensitive and PTX‐resistant breast cancer cells. BIRC5 expression is related to the poor survival of patients with breast cancer. Depletion of BIRC5 strengthened PTX‐induced viability reduction and promotion of apoptosis in MCF‐7 and MCF‐7/PTX cells. Moreover, BIRC5 overexpression reversed the inhibitory effect of crocin on PTX resistance in breast cancer cells. In conclusion, crocin enhanced the sensitivity of PTX in breast cancer cells partially through inhibiting BIRC5 expression. [ABSTRACT FROM AUTHOR]

AIM： To investigate whether crocin alleviates right ventricular injury induced by monocrotaline (MCT) in rats with pulmonary arterial hypertension (PAH), and to explore the underlying mechanisms. METHODS： Forty male SD rats were randomly divided into 4 groups： normal group, PAH group, crocin group and sildenafil group, with 10 rats in each group. The rats in PAH, crocin and sildenafil groups received subcutaneous injection of MCT (50 mg/ kg) to establish the PAH model. Starting from the day of MCT injection, the rats in crocin group received crocin (200 mg/ kg), the rats in sildenafil group received sildenafil (30 mg/kg), and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily. After 4 weeks, measurements of right ventricular systolic pressure (RVSP), mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and right ventricular mass index (RVMI) were taken for the rats in each group. Tissue staining was conducted to observe pathological changes in the right ventricle, and the expression levels of inflammatory factors (IL-1β, IL-6 and TNF-α), the p38 MAPK/NF-κB inflammatory pathway, CCL2, CCR2, and the macrophage marker CD68 were assessed. RESULTS： Compared with PAH group, the rats in crocin and sildenafil groups exhibited significant reductions in RVSP, mPAP, RVHI and RVMI (P<0. 05) . Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers. The downregulation of the p38 MAPK/NF- κB pathway and inflammatory factors (IL-1β, IL-6 and TNF- α) was significant (P< 0. 05) . Additionally, the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased (P< 0. 05) . CONCLUSION： Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats, with its efficacy comparable to that of sildenafil at the dosage utilized in this experiment. Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation. [ABSTRACT FROM AUTHOR]

Objective(s): Colistin is used to treat multidrug-resistant gram-negative bacterial infections. It increases the membrane permeability of kidney cells, leading to kidney toxicity. Crocin, a carotenoid found in saffron, has anti-oxidant and nephroprotective properties. The present study aimed to explore the potential renoprotective effects of crocin against colistin-induced nephrotoxicity. Materials and Methods: Six groups of male Wistar rats were utilized: 1-Control (0.5 ml of normal saline, 10 days, IP); 2- Crocin (40 mg/kg, 10 days, IP); 3-Colistin (23 mg/kg, 7 days, IP); 4-6 Colistin (23 mg/kg, 7 days, IP)+ crocin (10, 20, 40 mg/kg, 10 days, IP). On day 11, rats were sacrificed and their blood and kidney samples were collected to measure creatinine, blood urea nitrogen (BUN), glutathione (GSH) levels, malondialdehyde (MDA), and histopathological alterations. Results: Colistin caused a significant increase in BUN, creatinine, and MDA, and a decrease in GSH compared to the control group. It also led to congested blood vessels, glomerular shrinkage, and medullary tubular degeneration. Co-administration of crocin with colistin resulted in a significant decrease in BUN and creatinine, increased GSH levels, and ameliorated the histopathological alterations compared to the colistin group. No significant difference was found between the control group and the crocin (40 mg/kg) group. Conclusion: It might be suggested that colistin can induce kidney damage by inducing oxidative stress. However, crocin shows protective effects against colistin-induced renal injury by acting as an anti-oxidant. Hence, crocin can be used as a supplement to reduce tissue and biochemical damage caused by colistin injection. [ABSTRACT FROM AUTHOR]

Background and purpose: Stress is a stimulus that leads to a physical or psychological reaction. Stress affects memory and cognition. Common drugs for treating stress and memory disorders have limited effects and many side effects, so the search for new effective compounds with natural origin and fewer side effects is of interest. Various studies have shown that Terminalia chebula )T. chebula( and crocin are effective in improving memory. Several proteins, including synapsin-1, synaptophysin, and PSD95, are involved in the transmission of nerve messages in synapses involved in memory .In this study, the effect of the hydroalcoholic extract of T. chebula and crocin in improving memory and stress and the expression of synaptophysin, PSD 95, and synapsin-1 genes in the hippocampal tissue of male rats of the immobility stress model has been evaluated. Materials and methods: 25 adult male Wistar rats were randomly divided into five groups, including a control group, a stress group, treated with hydroalcoholic extract of T. chebula group, treated with crocin group, simultaneously treated with hydroalcoholic extract of T. chebula, and crocin group. All groups except the control group were subjected to immobility stress for 14 days. Crocin was injected intraperitoneally (30 mg/kg) and hydroalcoholic extract of T. chebula was given as intragastric gavage (50 mg/kg). After fourteen days, the shuttle box test was performed to check the memory, then the animals were anesthetized and their hippocampal tissue was isolated, and the expression changes of synapsin-1, synaptophysin, and PSD 95 genes in the tissue were analyzed by Real-time PCR method. Results: Immobility stress caused disruption in two memory indicators, i.e. increased the duration of staying in the dark chamber (P˂0.01) and decreased the latency time to enter the dark chamber compared to the control group (P˂0.0001). Treatment with the alcoholic extract of T. chebula did not affect the duration of staying in the dark chamber (P>0.05), but crocin decreased it compared to the stress group (P˂0.05). The hydroalcoholic extract of T. chebula and crocin increased the latency time to enter the dark chamber compared to the stress group (P˂0.01 and P˂0.001, respectively). As a result, both of them affected memory improvement parameters. The combination of the hydroalcoholic extract of T. chebula and crocin decreased the duration of staying in the dark chamber (P˂0.05) and increased the latency time to enter the dark chamber compared to the stress group (P˂0.001). Also, Immobility stress decreased the expression of synaptophysin, synapsin-1, and PSD95 genes in the hippocampus tissue compared to the control group (P˂0.001 for all genes). The expression of synaptophysin, synapsin-1, and PSD95 genes in the hippocampus tissue of groups treated with hydroalcoholic extract of T. chebula (P˂0.01, P˂0.01 and P˂0.001, respectively), crocin (P˂0.001, P˂0.01 and P˂0.001, respectively), and their combination (P˂0.001, P˂0.001 and P˂0.01, respectively), increased compared to the stress group. Conclusion: treatment with crocin and hydroalcoholic extract of T. chebula separately or their combination was effective in improving memory and reducing stress by increasing the expression of synapsin 1, synaptophysin, and PSD95 genes. [ABSTRACT FROM AUTHOR]

Corneal diseases are a major cause of vision loss, often associated with aging, trauma and disease. Damage to corneal sensory innervation leads to discomfort and pain. Environmental stressors, such as short-wavelength light, can induce oxidative stress that alters mitochondrial function and affects cell and tissue homeostasis, including corneal innervation. Cellular antioxidant mechanisms may attenuate oxidative stress. This study investigates crocin, a derivative of saffron, as a potential antioxidant therapy. In vitro rat trigeminal sensory ganglion neurons were exposed to both sodium azide and blue light overexposure as a model of oxidative damage. Crocin was used as a neuroprotective agent. Mitochondrial and cytoskeletal markers were studied by immunofluorescence analysis to determine oxidative damage and neuroprotection. In vivo corneal innervation degeneration was evaluated in cornea whole mount preparations using Sholl analyses. Blue light exposure induces oxidative stress that affects trigeminal neuron mitochondria and alters sensory axon dynamics in vitro, and it also affects corneal sensory innervation in an in vivo model. Our results show that crocin was effective in preserving mitochondrial function and protecting corneal sensory neurons from oxidative stress. Crocin appears to be a promising candidate for the neuroprotection of corneal innervation. [ABSTRACT FROM AUTHOR]

Background: Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains. Results: Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L). Conclusions: This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries. [ABSTRACT FROM AUTHOR]

Saffron (Crocus sativus L.) is the most expensive spice in the world. Saffron is costly due to the meagre yield per acre and exorbitant manpower costs. The three key compounds in saffron are crocin, picrocrocin and safranal, which are responsible for its colour, bitterness and flavour, respectively. The aim of this study was to exploit the bittering, aromatic and colouring properties of saffron to formulate a craft beer with refined taste and colour. As a result of the elevated price of the raw material, the saffron extraction process was optimised to achieve the best results using as little spice as possible. Thus, the extraction yields of two different methods were ascertained. To assess the ideal concentration of saffron to obtain a beverage with a balanced taste, three beers containing increasing concentrations of the spice were brewed. Then, once a sensory test was performed, another three samples were produced with the minimum dose of the spice (50 mg/L), added at various times during the production process (at 5 and 20 min before the end of the boiling stage, during the whirlpool stage and during refermentation). The purpose was to evaluate the consequences of heat treatment on crocin, picrocrocin and safranal compounds provided to the beer. All of the beer samples underwent routine analyses (alcoholic strength, Plato, IBU, colour and pH) and were analysed by spectrophotometry. [ABSTRACT FROM AUTHOR]

Buffalo bull sperm suffer more cryoinjuries due to lipid peroxidation of high structural polyunsaturated fatty acid contents than cattle sperm. Consequently, the post‐thaw fertilization potential of buffalo bull sperm is compromised. Crocin is a carotenoid known for its antioxidant potential through scavenging reactive oxygen species. Objectives of the current study were to investigate the effect of crocin addition in the semen extender on post‐thaw quality, fertility‐associated gene expression and fertilization potential of buffalo bull sperm. Semen samples (n = 32) from four Nili‐Ravi buffalo bulls were extended with tris‐citric acid extender containing different concentrations of crocin (0 mM; control, 0.5, 1, 1.5 and 2 mM). The extended semen was packed in 0.5 mL French straws (25 × 106 sperm/straw) and cryopreserved in liquid nitrogen. Computer‐assisted semen analysis, hypo‐osmotic swelling test, normal apical ridge assay, Rhodamine 123, acridine orange, propidium iodide staining, and thiobarbituric acid reactive substances assay were performed to assess sperm motility parameters, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential, DNA integrity, viability, and lipid peroxidation, respectively. Expression levels of sperm acrosome‐associated SPACA3, DNA condensation‐related PRM1, anti‐apoptotic BCL2, pro‐apoptotic BAX, and oxidative stress‐associated ROMO1 genes were evaluated through qPCR. The fertility of semen doses containing the most potent concentration of crocin (based on optimum post‐thaw semen quality) was compared with control during the breeding season. Buffaloes (n = 400; 200/group) were inseminated 24 h after the onset of oestrus and transrectally palpated for pregnancy at least 60 days post‐insemination. Results revealed that 0.5 and 1 mM crocin improved sperm post‐thaw total motility, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential and viability, and 1 and 1.5 mM crocin enhanced catalase activity and reduced lipid peroxidation compared to control (p <.05). Moreover, 1 mM crocin improved sperm post‐thaw progressive motility, kinematics, and DNA integrity, and 1.5 mM crocin enhanced plasma membrane integrity than control (p <.05). Expression levels of SPACA3, PRM1 and BCL2 genes were higher (p <.05) with 1 mM crocin compared to other groups. In contrast, no difference (p >.05) was noticed in expressions of BAX and ROMO1 genes among all groups. The fertility rate of semen doses containing the most potent concentration (1 mM) of crocin was higher (p =.0465) compared to control (56 ± 0.03% vs. 46 ± 0.04%, respectively). In conclusion, 1 mM crocin in the semen extender improves post‐thaw quality, fertility‐associated gene expression and fertilization potential of buffalo bull sperm. [ABSTRACT FROM AUTHOR]

Cyclophosphamide is a drug used in chemotherapy. However, it has side effects, including changes in reproductive system functioning. Some herbal compounds can reduce the harmful effects of cyclophosphamide. This study aims to investigate the protective role of crocin against changes caused by Cyclophosphamide in ovarian tissue through changes in the expression of genes involved in the hypothalamic-pituitary-gonadal axis. This experimental study was performed on 24 adult female Wistar rats. Mice were divided into four groups (normal saline, 30 mg/kg cyclophosphamide, 100 mg/kg crocin and 30 mg/kg cyclophosphamide, and 200 mg/kg crocin and 30 mg/kg cyclophosphamide). At the end of the treatment period, the hypothalamus and ovaries were also removed to evaluate ob-Rb, ob-Ra, and NPY genes expression using real-time PCR and histological changes in the ovaries. Data were analyzed by SPSS statistical software. The expression of genes, number of follicles, and follicle diameter significantly decreased in the cyclophosphamide-treated groups compared with the control group. In the crocin and cyclophosphamide-treated groups, drug-induced reproductive complications were mitigated. The current findings indicate that by increasing the expression of genes ob-Rb, ob-Ra, and NPY, crocin could modulate the harmful effects of cyclophosphamide. [ABSTRACT FROM AUTHOR]

Saffron Crocus sativus L. (Iridaceae) is one of the most valuable and expensive medicinal plants in the world. In order to compare the quality characteristics of saffron in Afghanistan and Iran, samples of dried C. sativus from different saffronproducing regions of Herat province (Afghanistan) and Torbat Heydarieh county (Iran) were collected in the year 2021. The experiment was analyzed in GLM format and Nested method with three replications. The samples of saffron produced from seven different districts of Herat province in Afghanistan, including Injil, Karukh, Guzara, Pashtun Zarghun, Zendeh Jan, Ghoryan, Obeh and nine saffronproducing villages (Fakhrabad, Kadkan, Nasar, Ghaleno, Feizabad, Khorgh, Abrood, Benhang, Shadmehr) of Torbat Heydarieh county in Iran were examined. The results showed that the effect of country and region (districts and villages) on the quality traits of saffron (crocin, picrocrocin and safranal) was significant. Moreover, the comparison of the mean values indicated the presence of significant differences in the qualitative characteristics of saffron among the different investigated villages of Torbat Heydarieh. The saffron produced in Afghanistan had the highest amount of crocin (on average 279.1 ɷ 440nm) and picrocrocin (on average 101 ϕ 257 nm), while the highest value of safranal (on average 34.2 θ 330 nm) was observed in saffron samples produced in Iran. The highest amount of the above quality traits belonged to the saffron of Zendeh Jan Herat region 5 (Af5, crocin: 303 ɷ 440 nm, picrocrocin: 106 ϕ 257 nm, safranal: 33 θ 330 nm), while the five Torbat Heydarieh villages had the lowest quality of saffron (Ir5, crocin: 164 ɷ 440nm, picrocrocin: 71 ϕ 257 nm, safranal: 34 θ 330 nm). In the comprehensive analysis of saffronproducing regions in Afghanistan and Iran, in terms of the qualitative attributes (crocin, picrocrocin, and safranal) it was evident that regions 1 to 6 in Herat, Afghanistan (Af1, Af2, Af3, Af4, Af5, Af6) and the Abrood village of Torbat Heidarieh, Iran (Ir7) formed a distinct cluster, demonstrating superior quality compared to other regions. Furthermore, with the exception of the Feizabad village of Torbat Heydarieh (Ir5), all examined samples surpassed the saffron ISO international standard and were categorized as firstgrade quality. The exceptional quality of Herat saffron from Afghanistan is likely attributable to the unique geographical features, virgin lands, and specific climatic conditions across diverse cultivation areas. [ABSTRACT FROM AUTHOR]

Integrated nutrient management is an environment friendly approach of plant nutrition being used for crop productivity and improvement in soil quality on sustainable basis. A three-year multi-location experiment was conducted to estimate the spice quality of saffron subjected to the integration of organic and inorganic nitrogen sources. At each location, the experiment was laid out in randomized complete block design. The treatments were T1 = control (without organic/inorganic N source/amendment); T2 = Full recommended nitrogen (i.e. urea fertilizer @ equivalent to 100 kg N ha−1; UN100); T3 = Poultry manure (PM) @ equivalent to 100 kg total N ha−1 (i.e. PM100); T4 = Farm yard manure (FYM) @ equivalent to 100 kg total N ha−1 (i.e. FYM100); T5 = PM50+FYM50; T6 = UN75 + PM25; T7 = UN50 + PM50; T8 = UN25 + PM75; T9 = UN75 + FYM25; T10 = UN50 + FYM50; T11 = UN25 + FYM75 and T12 = UN50 + PM25+ FYM25. Among treatments, poultry manure (100%) and urea nitrogen with poultry manure (UN50 + PM50) significantly affected the quality attributes of saffron. On the other hand, among sites, the crocin, picrocrocin and saffranal contents were in order of Khaigala (23.81% crocin, 20.01% picrocrocin and 0.27% saffranal) >Trarkhel (19.04% crocin, 16.99% picrocrocin and 0.25% saffranal) and > Abbaspur (17.80% crocin, 15.45% picrocrocin and 0.23% saffranal). Similarly, among years, the crocin, picrocrocin and saffranal contents were significantly higher in the third year compared to the first and second year. In conclusion, the integration of organic nitrogen sources with inorganic nitrogen has the potential to improve saffron quality. [ABSTRACT FROM AUTHOR]

Background & Aims: Azoospermia (lack of sperm in ejaculation) is one of the most severe types of infertility in men, due to various defects in the sperm production process or the testicular system . Azoospermia disease is caused by either obstructive mechanism (Obstructive azoospermia-OA) due to blockages in the natural sperm production system, or non-obstructive mechanism (NOA- Non obstructive azoospermia) due to defects in testicular sperm production, with over 60% of infertile men being afflicted with non-obstructive azoospermia (NOA). Treatment with busulfan may have adverse effects on various organs such as reproductive organs. Based on the understanding of hormonal control of sperm production, several drugs such as gonadotropins, androgens, estrogen receptor blockers, and aromatase inhibitors are used as experimental treatments for idiopathic male infertility. Letrozole, as an aromatase inhibitor, has been widely used in the treatment of female infertility, because the chemical structure of letrozole includes a triazole group that selectively interacts with the heme group of the enzyme P450arom, thereby reversibly inhibiting its biological activity Limited studies have evaluated the therapeutic potential of Letrozole in male infertility. In addition, excessive consumption of chemical drugs causes changes in the activity of antioxidant enzymes (TOS) and the stability of oxidative status (TAC) in the ROS pathway, leading to an imbalance between antioxidants and oxidants, resulting in oxidative stress. This phenomenon has led researchers towards the use of herbal medicines, which naturally have fewer side effects. Crocin has been identified as the main active biological component in saffron. Crocins are a type of water-soluble carotenoids that are either mono- or diglycosyl polyene esters, where D-gentiobiose and/or D-glucose appear as carbohydrate residues. A carotenoid with a 20-carbon dicarboxylic structure. Saffron contains various carotenoid chemicals that include small amounts of crocin, alpha and beta carotene, and lycopene. Six different forms of glycosylated esters from the crocin family have been found in saffron. Trans-crocins 3 and 4 are the most common analogs of crocins, which include crocins 1-4, and are essentially the glycosides of trans-crocin in saffron. Crocin can act as an antioxidant and improve the quality of sperm through increasing the expression of antioxidant genes. Therefore, phytoestrogens such as crocin bind to testicular estrogen receptors and stimulate spermatogenesis by strategies like increasing epithelial layers and the diameter of seminiferous tubules and lumen. The aim of this study was to investigate the synergistic effect of letrozole and crocin on the changes of antioxidant enzymes and testosterone hormone synthesis in the induction of spermatogenesis in azoospermia model mice with busulfan using ELISA technique. Methods: In this clinical trial, crocin and letrozole drugs were purchased from Sigma Aldrich. 30 male Wistar mice weighing 180-220 grams and aged approximately 8-10 weeks were purchased from the Pasteur Institute of Iran and transferred to the laboratory. They were kept under new conditions (at a temperature of 22-24 degrees Celsius, relative humidity of 55-60%, with a 12- hour light-dark cycle). To halt spermatogenesis and induce azoospermia, a dose of 10 mg/kg of busulfan was injected intraperitoneally for 10 days. Finally, the rats were divided into 5 groups of 6: the control group was injected with normal saline and citrate buffer inside the hemocoel; the treatment group received a single dose of 10 mg busulfan intra protanealat at a volume of 1.0 mL for 10 days; the treatment group was administered with a single dose of 10 mg busulfan intra protanealat at a volume of 1.0 mL, along with 5 mg letrozole with Black Soldier Fly (BSF) as the solvent; the treatment group received 15 mg crocin extract with normal saline, along with a single dose of 10 mg busulfan intra protanealat a volume of 1.0 mL; and the treatment group was given a single dose of 10 mg busulfan intra protanealat at a volume of 1.0 mL, along with 5 mg letrozole with BSF as the solvent, and 15 mg crocin extract with normal saline and underwent histopathological, histochemical immunological, and hormonal analyses. The data were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) with Tukey's post hoc test was used to compare the means in the study groups (P <0.05), and statistically significant differences were considered. Graphs were also plotted using Graph Prism software. Results: The results demonstrated that the simultaneous treatment of letrozole and crocin increased spermatogonia, spermatocytes, and spermatids; Sertoli and Leydig cells were also enhanced. Additionally, letrozole and crocin treatment led to the preservation of the thickness of the basement membrane and the germinal epithelium of testicular tissue; the inner and outer diameters of the tubules were increased. While in the azoospermia group treated with letrozole or crocin, this level of population destruction was somewhat reduced; however, the use of letrozole or crocin in the study groups did not show a significant difference in the inner and outer diameter of the tubules. Biochemical analysis showed a significant increase in the activity of the Total Antioxidant Capacity (TAC) enzyme activity and testosterone hormone levels in the group treated with letrozole + crosine compared to the azoospermia group; however, a significant decrease was found in the letrozole or crosine treatment group compared to the control group, while the Total Oxidant Status (TOS) enzyme activity in the letrozol+crosine treatment group showed a significant decrease compared to the azoospermia group(P<0.05). Conclusion: Some of the improvements in sperm parameters can be attributed to the antioxidant properties of crocin. It seems that sperm lose a large volume of their cytoplasm due to lack of antioxidants during spermatogenesis and become more sensitive to increases in ROS. These results indicate that crocin can act as an antioxidant and enhance sperm quality by increasing the expression of antioxidant genes. Therefore, the use of a plant-derived antioxidant like crocin appears necessary without any side effects and with essential strengthening effects. Crocin can likely act as an antioxidant and potentially improve sperm quality due to its antioxidant activity. Additionally, it has been found that letrozole improves spermatogenesis without causing any observable pathological changes in testicular tissue. According to the studies of Ribeiro et al, Uzun et al, and Shoshany and colleagues, letrozole reversibly inhibits the aromatase enzyme and prevents the conversion of androgen precursors to estradiol in adipose tissue. Moreover, crocin can neutralize the negative effects of oxidative stress and increase cell ability to overcome oxidative stress conditions by preventing glutathione reduction and increasing antioxidant capacity. One of the limitations of the research can be attributed to the lack of studies and sample restrictions, as well as the death of mice during the experimental process. Further investigations and focusing on the precise dosage of crocin, along with attention to the relevant mechanisms of action, seem essential. Overall, crocin has antioxidant and defensive effects, improves the quality of some sperms, and increases morphology, viability, motility, and natural count. In fact, testosterone regulates the secretion of LH hormone from the anterior pituitary gland through a negative feedback mechanism. Busulfan induced apoptosis in germinal epithelial cells and co-administration of letrozole and crocin reduced busulfan-induced apoptosis leading to infertility; therefore, a rational relationship between apoptosis of spermatogonia in response to busulfan exposure can be obtained. It can be suggested that crocin, one of the key components of saffron, acts as a potent antioxidant that can prevent the toxic effects of busulfan and DNA damage that may occur due to oxidative stress. [ABSTRACT FROM AUTHOR]

Saffron is a well-known expensive spice, which has many pharmacological properties against a variety of ailments. Saffron stigma and leaf contain apocarotenoids and bioactive phytochemicals having therapeutic potential against human disorders. Polycyclic aromatic hydrocarbons (PAHs) are one of the most common toxins in today's aquatic environment. Benzo[a]pyrene (B[a]P), a high molecular weight PAHs prototype, and reported as a potent neurotoxicant, which is profoundly contaminating the environment. The present study investigated the therapeutic efficacy of Saffron stigma extracts and crocin, on B[a]P-induced behavioral changes, altered antioxidant activities, and neurodegeneration in zebrafish. The behavioral responses monitored through the light-dark preference test and novel tank diving test suggested that B[a]P treated zebrafish group showed alteration in anxiolytic-like behavior. Animals exhibited their native behavior when treated alone with Saffron Stigma Extract (SSE) and crocin, an apocarotenoid which also reduced the altered behavior induced by B[a]P. The SSE and crocin stimulated the antioxidant activities with an accumulation of reduced glutathione and catalase enzymes, indicating a protective role against B[a]P-induced oxidative stress and behavioral deficits. The histopathological studies showed the percentage change of pyknotic cell counts in the Periventricular Gray Zone region of the Optic Tectum was 1.74 folds high in B[a]P treated animals as compared to control. Furthermore, the treatment of SSE and crocin reduced the pyknosis process induced by B[a]P-mediated neurodegeneration, possibly due to a better protective mechanism. Future studies may reveal the detailed mechanisms of action of potent SSE and crocin like bioactive compounds having neuroprotective potentials against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Diabetes increases the production of free radicals and inflammatory agents in the heart tissue and alters the expression of genes associated with the induction of apoptosis. Considering the importance of common cardiovascular disorders in diabetes, this study investigated the effect of eight weeks of aerobic exercise and crocin use, as well as tissue damage and oxidative stress caused by diabetes in the hearts of adult rats. Streptozotocin 50 mg/kg was injected as a single dose intraperitoneally to cause the diabetes. After 72 hours, a glucometer monitored blood glucose levels, and blood glucose above 250 mg/dl was considered diabetes. Continuous treadmill exercise was performed for eight weeks by placing the animal on the treadmill. Next, the animals were anesthetized, and samples were taken from the hearts and frozen in liquid nitrogen. Then, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured in the cardiac tissue. Finally, the hearts of half of the animals were immediately immersed in a formalin solution for histological changes. According to our findings, diabetes increased lipid peroxidation, characterized by increased MDA levels in the control diabetes group and decreased SOD and GPx levels (P <0.05). It also changes the balance of expression of genes associated with apoptosis control, increased Bcl-2-associated X (Bax) expression, and decreased Bcl-2 expression (P <0.05). Also, we observed the induction of apoptosis in cardiac tissue. Using eight weeks of continuous exercise and administration of crocin significantly reduced blood sugar levels and lipid peroxidation and increased the activity of antioxidant enzymes and Bcl-2 gene expression compared to the diabetes control group. In addition, continuous exercise and crocin improved the oxidative stress parameters in the control group. This study showed that diabetes could cause oxidative stress and heart dysfunction. Moreover, simultaneously and separately, aerobic exercise with a treadmill and crocin administration can reduce these disorders and prevent apoptosis in the heart tissue. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is a glomerular disease. Crocin is isolated from saffron and gardenia. Its antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-atherosclerotic, anti-tumor, free-radical scavenging and neuroprotective activities have been well established. We investigated the biological functions of crocin and its related mechanisms in MN. We established an experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum. The rats were divided into sham, sham + crocin, PHN, PHN + crocin, and PHN + enalapril groups. Blood samples and kidneys of rats were collected for estimation of biochemical parameters in serum and oxidative stress indicators in kidney tissues. Histopathological changes of renal tissues were evaluated by hematoxylin and eosin, periodic acid-Schiff (PAS) and Masson staining. The podocyte number was estimated by immunohistochemistry staining of Wilms tumor type 1 (WT1). The deposition of rat anti-rabbit IgG antibodies, complement C3 and C5b-9 was detected by immunofluorescence staining. Western blotting was performed to measure the levels of Sirtuin 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and apoptosis-related proteins. The total cholesterol, triglycerides, creatinine, blood urea nitrogen, urine volume and urine albumin of PMN rats were significantly reduced by crocin. Additionally, crocin attenuated the renal histopathological changes. Moreover, the oxidative stress damage and podocyte loss and immune injury were relieved by crocin in PHN rats. Mechanistically, crocin administration activated the Sirt1/Nrf2/HO-1 pathways. The results provide a scientific basis that crocin could alleviate MN by inhibiting immune injury and podocyte damage through activating the Sirt1/Nrf2/HO-1 pathways. [ABSTRACT FROM AUTHOR]

Objective To investigate the cardioprotective effect of Saffron (Crocus sativus L.) treatment as a potential supplement on patients with type 2 diabetes mellitus (T2DM). Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to analyze articles retrieved from PubMed, ScienceDirect, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) with a publication time span from January 15, 2015 to March 20, 2023. The articles were published in English only, including randomized controlled trials (RCTs) on adult patients who were diagnosed with T2DM, and received either Saffron or placebo treatment. Meta-analysis was performed using Review Manager 5.4 software. The present study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with a registration number as CRD42023443180. Results Seven RCTs with 455 patients were included in the study. The data revealed that Saffron treatment significantly reduced tumor necrosis factor (TNF)-α (P = 0.008) and fasting blood glucose (FBG) (P = 0.04) levels compared with what placebo did in T2DM patients. No significant differences were shown in the levels of interleukin (IL)-6, malondialdehyde (MDA), high serum C-reactive protein (hs-CRP), lipid profile, blood pressure, and body mass index (BMI) between Saffron and placebo (P > 0.05). Conclusion Saffron treatment has a cardioprotective effect in T2DM patients by reducing TNF-α and FBG levels. However, the potential anti-oxidant, anti-hypertensive, and anti-dyslipidaemia effects of the phytochemical need to be further investigated. [ABSTRACT FROM AUTHOR]

Drying of the delicate, red stigmas of the Crocus sativus L. flower is necessary to produce saffron, the most expensive spice in the world. So far, laborious and sample destructive methods were applied to get vital insight into this process following key physicochemical changes. Vibrational spectroscopy tools that allow molecular fingerprinting of plant tissues via multivariate data analysis are still not exploited. This study aimed at gaining new insights into the Fourier-Transform Infrared (FTIR) spectra of saffron on different gentle drying treatments in vacuum or by short-time heating with varying sample loading, energy input, duration etc. Diagnostic spectral bands that were exposed using Principal Component Analysis were assigned to C=O stretching in vinyl or cyclic esters, amides or other inter-molecular interactions of importance for functionality. Above all, the peak at 1160 cm−1 (typical of C-O-C glycosidic bridges) proved a distinguishing feature of short-time heated vs vacuum-dried saffron. Other critical quality attributes of the dried stigmas (physical structure, color, chemical composition), assessed with Scanning Electron Microscopy (SEM), colorimetry, UV-Vis spectrometry and High-Performance Liquid Chromatography (HPLC), indicated both positive and negative effects per drying method. Our work highlights the novelty to combine non-destructive FTIR spectroscopy with conventional techniques for a more insightful evaluation of desired or undesired changes after saffron dehydration. Moreover, the spectral fingerprinting approach offers a cost-effective, eco-friendly solution for rapid, non-invasive control of the raw material that is of high interest for food and nutraceutical applications. [ABSTRACT FROM AUTHOR]

• Saffron stigmas crop generates a large amount of biomass called by-product with high added value. • Saffron floral by-products (tepals, leaves, stamens, styles, spaths, and others) are rich in flavonoids, anthocyanins, carotenoids, and volatile compounds. • Chemical compounds contained in the saffron floral by-products have excellent antioxidant and anti-microbiological activities. • Bioactive compounds of saffron floral by-products are a great coloring and aromatic agents strongly used in industrial formulations. Saffron (Crocus Sativus L.), is the most expensive spice in the world, derived from the red filaments (stigmas) of a sterile triploid geophyte plant that belongs to the Iridaceae family. Saffron stigmas have been traditionally used in food and cosmetic products due to their coloring, flavoring, and aromatic aspects, attributed to their bioactive compounds, namely crocin, picrocrocin, and safranal. After harvesting saffron stigmas, a considerable amount of saffron floral parts so-called by-products are generated: petals, leaves, stamens, and others. Recent scientific studies have focused on cosmetic, therapeutic, and nutraceutical applications of not only saffron stigmas but also their several floral by-products. The chemical compounds contained in the whole saffron flower such as polyphenols, flavonoids, and anthocyanins, are endowed with excellent potentialities like antioxidant, and antimicrobial activities which makes them strongly used in food and cosmetic products. This paper aims to provide a systematic overview of specialized (secondary) metabolites applications of saffron stigmas as well as its by-products in various fields, also, the mechanisms of action of saffron bioactive compounds activities have been explained in this paper. [ABSTRACT FROM AUTHOR]

Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area. [ABSTRACT FROM AUTHOR]

Estrogen deficiency intensifies sarcopenia by activation of inflammatory and oxidative pathways. Aerobic exercise training and antioxidant/inflammatory supplements might reverse such outcomes or decline the degenerative pathway. Thus, we investigated the impact of aerobic training and crocin (CRO) consumption on skeletal muscle MuRf-1 and plasma antioxidant and inflammatory statues in ovariectomized (OVX) rat models fed on a high-fat diet (HFD). 72 female Wistar rats (200 ± 20 gr) were randomly divided into 9 groups: (1) non-OVX + standard chow (nOVX + SC), (2) nOVX + HFD, (3) high-intensity continuous training (HICT) + OVX + HFD + CRO, (4) HICT + OVX + HFD, (5) moderate-intensity continuous training (MICT) + OVX + HFD + CRO, (6) MICT + OVX + HFD, (7) OVX + HFD + CRO, (8) OVX + SC, and (9) OVX + HFD. The OVX rats underwent surgery for menopause model induction. Immediately after the ovariectomy, rats were fed either by HFD or SC. Seven weeks later, exercise training (HICT/MICT; 8-week, 5-session, 12–30 m/min or 12–21 m/min) and CRO consumption (60 mg/kg) intervention per sessions were performed. The plasma levels of SOD, GSH, and TNF-α and muscle levels of MuRf-1 were assessed using the ELISA method. A two-tailed t-test and one-way ANOVA were applied for data analysis. There was not a significant difference in the protein levels of MuRF1 as the CRO caused an increase in the TNF-α levels as compared to the control. HICT significantly decreased SOD levels as compared to the control, CRO, and MICT. There was no significant difference in GSH levels between intervention arms. Exercise training and CRO supplementations did not make any significant changes in muscle mass regulation factors in the OVX rat model. [ABSTRACT FROM AUTHOR]

Objective(s): Macrophages exhibit versatile phenotypes, with M1 macrophages releasing inflammatory cytokines and possessing microbicidal activities, while M2 macrophages release antiinflammatory cytokines and contribute to tissue repair. The M1/M2 imbalance plays a significant role in various pathological processes. Crocin, known for its antioxidant properties and ability to eliminate free radicals, has been investigated for its potential anti-inflammatory effects. We examined the effect of the primary activation state of macrophages on their phenotype switching when exposed to crocin. Materials and Methods: The crocin impact on macrophage viability was evaluated by MTT. TNF-α, IL-6, and IL-10 secretion, as well as Nos2/Arg1 ratio, were measured in cells treated with crocin or LPS+IFN-γ (M1 inducers), in cells concurrently treated with crocin and LPS+IFN-γ or in cells pretreated with crocin before M1 induction. Results: Crocin did not show any toxicity at the concentration of 500 μM or lower. When uncommitted macrophages were exposed to crocin (25-100 μM), it elevated certain M1 activity indicators, including Nos2/Arg1 ratio and TNF-α secretion, but not IL-6. Crocin in concurrent treatment with LPS+IFN-γ prevented the increase in M1 indicators, Nos2/Arg1 ratio, and TNF-α secretion. However, pretreatment of cells with crocin before the addition of LPS+IFN-γ did not reverse M1 induction in macrophages; instead, it further increased the Nos2/Arg1 ratio and TNF-α secretion. IL-10 was not detectable in any of the experimental groups. Conclusion: It appears that the modulatory effects of crocin on macrophage M1/M2 phenotype switching partly depend on the presence or absence of inflammatory mediators and, accordingly, the initial state of macrophage commitment. [ABSTRACT FROM AUTHOR]

The night‐flowering Jasmine, Nyctanthes arbor‐tristis also known as Parijat, is a perennial woody shrub belonging to the family of Oleaceae. It is popular for its fragrant flowers that bloom in the night and is a potent source of secondary metabolites. However, knowledge about its genome and the expression of genes regulating flowering or secondary metabolite accumulation is lacking. In this study, we generated whole genome sequencing data to assemble the first de novo assembly of Parijat and use it for comparative genomics and demographic history reconstruction. The temporal dynamics of effective population size (Ne) experienced a positive influence of colder climates suggesting the switch to night flowering may have provided an evolutionary advantage. We employed multi‐tissue transcriptome sequencing of floral stages/parts to obtain insights into the transcriptional regulation of nocturnal flower development and the production of volatiles/metabolites. Tissue‐specific transcripts for mature flowers revealed key players in circadian regulation and flower development, including the auxin pathway and cell wall modifying genes. Furthermore, we identified tissue‐specific transcripts responsible for producing numerous secondary metabolites, mainly terpenoids and carotenoids. The diversity and specificity of Terpene Synthase (TPS) and CCDs (Carotenoid Cleavage Deoxygenases) mediate the bio‐synthesis of specialised metabolites in Parijat. Our study establishes Parijat as a novel non‐model species to understand the molecular mechanisms of nocturnal blooming and secondary metabolite production. [ABSTRACT FROM AUTHOR]

Crocins are important natural products predominantly obtained from the stigma of saffron, and that can be utilized as a medicinal compound, spice, and colorant with significant promise in the pharmaceutical, food, and cosmetic industries. Carotenoid cleavage dioxygenase 2 (CsCCD2) is a crucial limiting enzyme that has been reported to be responsible for the cleavage of zeaxanthin in the crocin biosynthetic pathway. However, the catalytic activity of CsCCD2 on β-carotene/lycopene remains elusive, and the soluble expression of CsCCD2 remains a big challenge. In this study, we reported the functional characteristics of CsCCD2, that can catalyze not only zeaxanthin cleavage but also β-carotene and lycopene cleavage. The molecular basis of the divergent functionality of CsCCD2 was elucidated using bioinformatic analysis and truncation studies. The protein expression optimization results demonstrated that the use of a maltose-binding protein (MBP) tag and the optimization of the induction conditions resulted in the production of more soluble protein. Correspondingly, the catalytic efficiency of soluble CsCCD2 was higher than that of the insoluble one, and the results further validated its functional verification. This study not only broadened the substrate profile of CsCCD2, but also achieved the soluble expression of CsCCD2. It provides a firm platform for CsCCD2 crystal structure resolution and facilitates the synthesis of crocetin and crocins. [ABSTRACT FROM AUTHOR]

On average, depression affects 7.7% of the population aged 15 and older. One of the types of medicinal plants used to treat depression is saffron, which is uplifting and relieves sadness. Crocin as a bioactive compound is effective against depression, but it is sensitive to temperature, pH, and oxygen, and its efficiency decreases. Nanoencapsulation of crocin using double-layer emulsions is a method to increase the stability of this compound. Surfactant ratio (50% to 200%), stirrer speed (500 and 1000 rpm), and stirring time (45, 90, and 135 min) were used as variables of primary emulsion production. The optimum ratio of surfactant to aqueous phase was 100%, and in all microemulsions, viscosity increased with increasing surfactant ratio. A high-pressure homogenization method was used to make the secondary emulsion (double-layer emulsions), and soy protein concentrate (SPC), Gum Arabic (GA), and Pectin (P) at two levels of 5 and 10% were used to increase the stability. All treatments evaluated using Duncan's test at a significance level of 5%. Double-layer emulsions stabilized with pectin showed the highest viscosity and the lowest release of crocin in simulated stomach and intestine conditions. The use of the cellular automata model to investigate the release of crocin showed that this model could simulate the effects of crocin concentration, polymer concentration, and the droplet size of double-layer emulsions with 93–99% confidence to predict the release in double-layer emulsions. Then the double-layer emulsions added to the chocolate, and the chocolate containing the double-layer emulsions compared with the control sample in terms of sensory properties and had a higher score than the control sample. [ABSTRACT FROM AUTHOR]

Autism is a neurobehavioral disease that induces cognitive and behavioral alterations, usually accompanied by oxidative stress in the brain. Crocus sativus (saffron) and its active ingredient, crocin, have potent antioxidative effects that may benefit autistic behaviors. This study aimed to determine the effects of saffron extract and crocin against brain oxidative stress and behavioral, motor, and cognitive deficits in an animal model of autism in male offspring rats. 14 female rats were randomly divided into the saline and valproic acid (VPA) groups. Then, they were placed with mature male rats to mate and produce offspring. VPA (500 mg/kg, i.p.) was injected on day 12.5 of pregnancy (gestational day, GD 12.5) to induce an experimental model of autism. 48 male pups were left undisturbed for 29 days. First-round behavioral tests (before treatments) were performed on 30–33 post-natal days (PND), followed by 28 days of treatment (PND 34–61) with saffron (30 mg/kg, IP), crocin (15 or 30 mg/kg, i.p.), or saline (2 ml/kg, i.p.). The second round of behavioral tests (after treatments) was performed on PND 62–65 to assess the effects of the treatments on behavioral and cognitive features. In the end, animals were sacrificed under deep anesthesia, and their brains were dissected to evaluate the brain oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT). VPA injection into female rats increased anxiety-like behaviors, enhanced pain threshold, impaired motor functions, disturbed balance power, increased MDA, and decreased GSH and CAT in their male offspring. 28 days of treatment with saffron or crocin significantly ameliorated behavioral abnormalities, reduced MDA, and increased GSH and CAT levels. Brain oxidative stress has been implicated in the pathophysiology of autistic-like behaviors. Saffron and crocin ameliorate anxiety-like behaviors, pain responses, motor functions, and brain oxidative stress parameters in an experimental model of autism. Saffron and crocin may hold promise as herbal-based pharmacological treatments for individuals with autism. However, further histological evidence is needed to confirm their efficacy. [ABSTRACT FROM AUTHOR]

The role of Crocin, which is a natural organic substance from the Greek plant Crocus sativus, is investigated as a green corrosion inhibitor for the AA 1050 commercial aluminum alloy in 0.01 M sodium chloride solution. Its action was assessed by Linear and Tafel Polarization, as well as by mass loss measurements and confirmed by observation and analysis of the surface morphology of the specimens by Scanning Electron Microscopy. Corrosion inhibition efficiency of Crocin improves with concentration and at 1.25 mM was estimated in the range of 90-95%, which indicates the formation of an adsorbed layer that isolates and protects the surface. Experimental results showed that Crocin acts as a mixed-type inhibitor with predominantly anodic effectiveness, also retarding pitting corrosion process. The inhibitive action of Crocin was explained by theoretical calculations employing density functional theory, semiempirical PM6 and molecular mechanics methodologies, showing good agreement with experimental results. The reactivity of Crocin is attributed to chemisorption on the Al2O3 surface through its vicinal hydroxyls of the sugar moiety. This process is assisted by the π-conjugated system of the polyene chain together with the extended electron delocalization over the oxygen atoms of the esterified carboxyl groups, as well as by the intense electrostatic potential regions located on the sugar moiety of the Crocin molecule. [ABSTRACT FROM AUTHOR]

The potential therapeutic benefits of saffron and its active constituents have been investigated for the treatment of numerous illnesses. In this review, the impacts of saffron and its essential components on the levels of microRNAs (miRNAs) in different diseases have been delineated. Relevant articles were obtained through databases such as PubMed, Web of Sciences, Scopus, and Google Scholar up to the end of November 2022. miRNA expression has been altered by saffron and its active substances (crocin, crocetin, and safranal) which has been of great advantage in treating diseases such as cardiovascular, type 2 diabetes, cancers, gastrointestinal and liver disorders, central and peripheral nervous system disorders, asthma, osteoarthritis, ischemic-reperfusion induced injury conditions, and renal disorder. This study uncovered the potential restorative advantages of saffron and its derivatives, in miRNA imbalances in a variety of diseases. [ABSTRACT FROM AUTHOR]

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer's disease. Crocins are mainly biosynthesized in the stigmas of food–medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco. [ABSTRACT FROM AUTHOR]

A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-β) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings. [ABSTRACT FROM AUTHOR]

Despite the proliferation of medications and therapies for cancer patients, cancer is an illness that significantly influences the expectancy and quality of life. Globally, there is a severe public health issue with cancer. Up-regulated differentiation, uncontrolled proliferation, and immortality are the most significant characteristics of cancer cells. Polyphenols, flavonoids, carotenoids, alkaloids, and other naturally occurring chemicals obtained from plants can be physiologically active and have various impacts. Crocin and crocetin, two carotenoids found in saffron (Crocus sativus Linn.), have mostly been investigated for their antioxidant characteristics and protective benefits. Being a water-soluble carotenoid and a bioactive component of saffron, crocin has antioxidant, antihyperlipidemic, memory-improving, and tumor growth-inhibiting properties. The current review sheds light on saffron and its phytoconstituents, crocin's anticancer mechanism, crocin in the treatment of various cancers, crocin-based nano drug delivery systems, crocin's toxicity, and safety issues, as well as patents for cancer treatments based on saffron phytoconstituents. [Display omitted] • The dried stigma of Crocus sativus L. flowers is used as a source of saffron. • Crocin, crocetin, and safranal carotenoids of C. sativus show anticancer activity. • Natural antioxidants check cellular damage by squelching free radical reactions. • Nano drug delivery systems improve crocin's bioavailability. [ABSTRACT FROM AUTHOR]

Aim: Islets of Langerhans are more sensitive to oxidative damage because of their low antioxidant capacity. In diabetes, methylglyoxal (MG) accumulates in the pancreas. The present study examined the effect of crocin on oxidative stress induced by MG in isolated Langerhans islets from male mice. Material and Methods: Twenty-four male mice weighing 20 to 25 g were prepared. The isolated Langerhans islets were transferred to the culture medium. Oxidative stress was induced through MG administration for 30 min, and then 10, 20, 30, and 40 μM of crocin was used for 2 h. Samples were divided into seven groups with 2.8, 5.6, and 16.7 mM glucose concentrations: control, MG 300 μM, MG+glibenclamide 10 μM, and MG+crocin in four doses of 10, 20, 30, and 40 μM. At the end, the islet's insulin, antioxidant levels, and lipid peroxidation were assessed by ELISA and calorimetry methods. Results: Increased levels of malondialdehyde (MDA) in MG groups significantly decreased in 2.8 (p=0.008), 5.6 (p=0.004), and 16.7 (p<0.001) mM glucose concentrations, with administration of 30 and 40 μM crocin. Total antioxidant capacity (TAC) was reduced in MG groups (p<0.001) and significantly restored in all crocin-treated groups in 2.8, 5.6, and 16.7 mM glucose concentrations. Also, a significant decrease in insulin secretion and content was observed in MG groups of all three glucose concentrations (p<0.001). Crocin at high doses improved these alterations. Conclusion: MG caused oxidative damage and reduced insulin secretion in isolated islets. Crocin improved the antioxidant defense system, diminished MDA, and increased insulin secretion. [ABSTRACT FROM AUTHOR]

Introduction: Microcin (Mcc) refers to a class of small-sized antimicrobial agents that are produced by various strains of Enterobacterales. Microcins exhibit potent bactericidal characteristics through intricate mechanisms that enable their ingress into both the outer and inner membranes of Gram-negative microorganisms. In this study, we investigated the antibacterial activity of microcins and the prevalence of Mcc genes among Escherichia coli (E. coli) strains. Simulation investigations were additionally carried out on the affixed complex for the purpose of ascertaining its stability. Methods: This cross-sectional investigation involved the collection of 125 urine and blood specimens during the years 2021 and 2022, from patients who referred to private diagnostic laboratories in Isfahan. Bacteriocin activity was assessed by the agar-well diffusion assay. The complete set of bacterial strains was assessed in order to detect the existence of five specific Mcc, namely B17, H47, J25, M and V. The impact of bacteriocin-producing strains on the growth of pathogenic multidrug-resistant (MDR) E. coli and Salmonella enterica serovar Typhimurium was evaluated by examining the bacterial growth in the culture medium in the presence of metabolites produced by the E. coli strains. Salmonella enterica serovar Typhimurium, which were treated and untreated with CFS, were observed by using the scanning electron microscope (SEM). AutoDock Vina 1.1.2. and AutoDock Tools 1.5.7 automated docking tools were employed to facilitate the docking of MccJ25 peptide with the active enzyme. Results: Out of 125 clinical specimens, 45 (representing 36% of the sample) demonstrated the presence of significant zones of inhibition in agar well diffusion assay. A total of 36 strains were ascertained to exhibit positivity for the existence of 5 Mcc genes. The cell-free supernatant (CFS), from the cellular lysate of E. coli exhibited inhibitory properties and did not exhibit a cytotoxic impact on the L929 cell line. Moreover, significant binding modes with high docking scores are in the range against selected pathogenic microorganisms. Conclusion: The characteristics of the bacteriocins synthesized by E. coli demonstrated efficacy against pathogenic bacteria, including Salmonella and MDR E. coli, thereby highlighting the substantial potential of bacteriocin as a promising antimicrobial agent. Furthermore, the cytotoxicity test results indicated the safety of its usage, thereby presenting intriguing biotechnological possibilities. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer represents one of the most lethal forms of cancer, with hepatocellular carcinoma (HCC) accounting for the majority of its incidences and deaths. Currently, sorafenib is the first-in-line option for treating advanced and unresectable HCC. It is a multi-kinase inhibitor that intervenes with tumor growth and progression. Considering the modest results provided by sorafenib, identifying novel approaches to treating HCC remains a clinical imperative. Based on our previous work, crocin, a constituent of saffron, prevented HCC development. This study aimed to investigate its therapeutic effect in combination with sorafenib against an induced model of hepatocellular carcinoma arising from a cirrhotic milieu in rats. Our results confirmed that combination therapy yielded more effective outcomes compared to crocin and sorafenib monotherapies. It exerted the most pronounced effects in inhibiting inflammation and tumor cell proliferation while activating apoptosis and restoring macroscopic and cellular liver morphology. These results introduce a potential strategy for optimizing the anticancer effects of sorafenib using the bioactive natural compound crocin against HCC. Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies, with continuously increasing cases and fatalities. Diagnosis often occurs in the advanced stages, confining patients to systemic therapies such as sorafenib. Sorafenib (SB), a multi-kinase inhibitor, has not yet demonstrated sufficient efficacy against advanced HCC. There is a strong argument in favor of studying its use in combination with other medications to optimize the therapeutic results. According to our earlier work, crocin (CR), a key bioactive component of saffron, hinders HCC development and liver cancer stemness. In this study, we investigated the therapeutic use of CR or its combination with SB in a cirrhotic rat model of HCC and evaluated how effectively SB and CR inhibited tumor growth in this model. Diethylnitrosamine (DEN) was administered intraperitoneally to rats once a week for 15 weeks, leading to cirrhosis, and then 19 weeks later, leading to multifocal HCC. After 16 weeks of cancer induction, CR (200 mg/kg daily) and SB (10 mg/kg daily) were given orally to rats for three weeks, either separately or in combination. Consistently, the combination treatment considerably decreased the incidence of dyschromatic nodules, nodule multiplicity, and dysplastic nodules when compared to the HCC group of single therapies. Combined therapy also caused the highest degree of apoptosis, along with decreased proliferating and β-catenin levels in the tumor tissues. Additionally, when rats received combined therapy with CR, it showed anti-inflammatory characteristics where nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (Cox-2) were considerably and additively lowered. As a result, CR potentiates the suppressive effects of SB on tumor growth and provides the opportunity to strengthen the therapeutic effects of SB in the treatment of HCC. [ABSTRACT FROM AUTHOR]