Showing papers on "Crocin published in 2020"

Tandem gene duplications drive divergent evolution of caffeine and crocin biosynthetic pathways in plants

Abstract: Plants have evolved a panoply of specialized metabolites that increase their environmental fitness Two examples are caffeine, a purine psychotropic alkaloid, and crocins, a group of glycosylated apocarotenoid pigments Both classes of compounds are found in a handful of distantly related plant genera (Coffea, Camellia, Paullinia, and Ilex for caffeine; Crocus, Buddleja, and Gardenia for crocins) wherein they presumably evolved through convergent evolution The closely related Coffea and Gardenia genera belong to the Rubiaceae family and synthesize, respectively, caffeine and crocins in their fruits Here, we report a chromosomal-level genome assembly of Gardenia jasminoides, a crocin-producing species, obtained using Oxford Nanopore sequencing and Hi-C technology Through genomic and functional assays, we completely deciphered for the first time in any plant the dedicated pathway of crocin biosynthesis Through comparative analyses with Coffea canephora and other eudicot genomes, we show that Coffea caffeine synthases and the first dedicated gene in the Gardenia crocin pathway, GjCCD4a, evolved through recent tandem gene duplications in the two different genera, respectively In contrast, genes encoding later steps of the Gardenia crocin pathway, ALDH and UGT, evolved through more ancient gene duplications and were presumably recruited into the crocin biosynthetic pathway only after the evolution of the GjCCD4a gene This study shows duplication-based divergent evolution within the coffee family (Rubiaceae) of two characteristic secondary metabolic pathways, caffeine and crocin biosynthesis, from a common ancestor that possessed neither complete pathway These findings provide significant insights on the role of tandem duplications in the evolution of plant specialized metabolism

Saffron bioactives crocin, crocetin and safranal: effect on oxidative stress and mechanisms of action.

Abstract: Saffron (Crocus sativus L.) is used as a spice for its organoleptic characteristics related to its coloring and flavoring properties, and it has been also used in traditional medicine to treat various diseases. The main chemical components responsible for these properties are crocin, crocetin and safranal. These compounds have been shown to have a wide spectrum of biological activities, including several properties as antigenotoxic, antioxidant, anticancer, anti-inflammatory, antiatherosclerotic, antidiabetic, hypotensive, hypoglycemic, antihyperlipidemic, antidegenerative and antidepressant, among others. This review article highlights the antioxidant effects of these bioactive compounds to reduce reactive oxygen species (ROS) and the mechanisms of action involved, since there are a multitude of diseases related to oxidative stress and the generation of free radicals (FRs). Recent studies have shown that the effects of crocin, crocetin and safranal against oxidative stress include the reduction in lipid peroxidation (malondialdehyde [MDA] levels) and nitric oxide (NO) levels, and the increase in the levels of glutathione, antioxidant enzymes (superoxide dismutase [SOD], catalase (CAT) and glutathione peroxidase [GPx]) and thiol content. Therefore, due to the great antioxidant effects of these saffron compounds, it makes saffron a potential source of bioactive extracts for the development of bioactive ingredients, which can be used to produce functional foods.

Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis.

Abstract: Crocin is isolated from saffron and has multiple activities. There are many reports on its beneficial effects for cardiovascular disease, but crocin’s effects on anti-myocardial fibrosis have not yet been reported. This study investigated crocin’s effects and potential mechanisms on isoproterenol (ISO)-induced myocardial fibrosis (MF) in mice. Mice were infused intraperitoneally with crocin with concurrent ISO subcutaneous injections over 2 weeks. Electrocardiography, cardiac weight index (CWI), hydroxyproline content, and heart morphology changes were observed. Administration of crocin markedly decreased heart rate, J-point elevation, QRS interval, CWI, and hydroxyproline content in the myocardial tissues, and improved heart pathologic morphology. Versus the control group, the ISO group showed an increase in lactate dehydrogenase and creatine kinase activities and malondialdehyde content. Meanwhile, superoxide dismutase, catalase, and glutathione contents decreased in the ISO group; crocin caused a significant reduction in oxidative stress levels in ISO-induced MF. ISO led to a significant increase in interleukin-1 and -6 and tumor necrosis factor-α in addition to nuclear factor kappa B (NF-κB) (p65) and toll-like receptor (TLR) 4 expressions. Crocin treatment suppressed these inflammatory cytokine expressions. Moreover, crocin treatment caused a significant decrease in connective tissue growth factor and transforming growth factor-β1 mRNA levels in addition to a decrease in B cell lymphoma-2, Bcl-2-associated X protein, caspase-3, and cleaved caspase-3 expressions. Crocin has a protective effect on ISO-induced MF, which may be associated with the TLR4/NF-κB (p65) signal transduction pathway.

Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Abstract: Organophosphorus compounds are widely used in agriculture. Epidemiological studies propose that pesticide exposure is a risk factor for Alzheimer’s disease (AD), but the mechanisms are unclear. Her...

Effects of crocin and saffron aqueous extract on gene expression of SIRT1, AMPK, LOX1, NF-κB, and MCP-1 in patients with coronary artery disease: A randomized placebo-controlled clinical trial.

Abstract: This trial evaluated the potential impacts of saffron aqueous extract (SAE) and its main carotenoid on some of the atherosclerosis-related gene expression and serum levels of oxidized low-density cholesterol (ox-LDL) and Monocyte chemoattractant protein 1 (MCP-1) in patients with coronary artery disease (CAD). Participants of this randomized controlled trial included 84 CAD patients who categorized into three groups: Group 1 received crocin (30 mg/day), Group 2 SAE (30 mg/day), and Group 3 placebo for 8 weeks. Gene expression of Sirtuin 1 (SIRT1), 5'-adenosine monophosphate-activated protein kinase (AMPK), Lectin-like oxidized LDL receptor 1 (LOX1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and MCP-1 in peripheral blood mononuclear cells assessed by real-time PCR. Furthermore, serum ox-LDL and MCP-1 levels measured at the beginning and end of the intervention. Compared with the placebo group, gene expression of SIRT1 and AMPK increased significantly in the crocin group (p = .001), and the expression of LOX1 and NF-κB decreased significantly (p = .016 and .004, respectively). Serum ox-LDL levels decreased significantly in the crocin group after the intervention (p = .002) while MCP-1 levels decreased both in crocin and SAE groups (p = .001). Crocin may have beneficial effects on CAD patients by increasing the gene expression of SIRT1 and AMPK and decreasing the expression of LOX1 and NF-κB.

Recent Advances on the Anticancer Properties of Saffron (Crocus sativus L.) and Its Major Constituents

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

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

Abstract: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet–dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence. This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism. Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats.

Abstract: Background:Liver fibrosis is a chronic pathological condition with a leading cause of liver-related mortality worldwide. In the present study, we have evaluated the antifibrotic effect of crocin, a...

Role of crocin in several cancer cell lines: An updated review.

Abstract: Cancer is a major public health problem worldwide. The most important considerable features of cancer cells are uncontrolled proliferation, up-regulated differentiation, and immortality. Crocin, as a bioactive compound of saffron and as a water-soluble carotenoid has radical scavenging, anti-hyperlipidemia, memory improving, and inhibition of tumor growth effects. The present review was designed to evaluate molecular mechanisms underlying crocin effects against cancer cell lines. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, and Scientific Information Database from 1982 to 2019. According to various literature, crocin inhibits tumor growth, and its spread in several types of cancer including colorectal, pancreatic, breast, and prostate, as well as chronic myelogenous and leukemia. It inhibits telomerase activity, microtubule polymerization, cyclin D1, nuclear factor kappa B (NF-kB), multidrug resistance-associated protein (MRP1), and MRP2 overexpression. Crocin can induce apoptosis through activation of caspase 8, up-regulation of p53 expression, Bax/Bcl-2 ratio, and down-regulation expression of Bcl-2, survivin, and cyclin D1. It also down-regulates matrix metalloproteinase 2 and 9 (MMP2 and MMP9), N-cadherin, and beta-catenin expression, which are involved in tumor invasion and metastasis. Tumor invasion was also inhibited by crocin through increasing E-cadherin expression, cell cycle suppression at G1, G0/G1, S, and G2/M phases. Crocin has therapeutic and preventive effects on cancer cells line. Therefore, it has been suggested that this agent can be administered in patients that suffer from this problem.

An updated review on therapeutic effects of nanoparticle-based formulations of saffron components (safranal, crocin, and crocetin)

Abstract: In recent years, nanotechnology has come to help researchers a lot in different fields. Especially in medicine and drug delivery, it presents new methods and technologies to increment levels of drug delivery to tumors and decrement side effects of drugs and molecules. Saffron, the dried stigma of the flower of the Crocus sativus plant, is one of the most widely used types of spice with many therapeutic applications that are related to its components: crocin, crocetin, and safranal. Saffron has been used as antispasmodic, anticatarrhal, eupeptic, nerve sedative, gingival sedative, diaphoretic, expectorant, carminative, stomachic, stimulant, emmenagogue, and aphrodisiac for years and now it has been made clear that it could have antioxidant, antidepressant, and anti-cancer activity. This review discusses how nanotechnology could help improve saffron’s pharmaceutical effects and makes it more functional in treatment.

Toxic Effects of Methotrexate on Rat Kidney Recovered by Crocin as a Consequence of Antioxidant Activity and Lipid Peroxidation Prevention

Abstract: Background The application of methotrexate (MTX) as a chemotherapy agent and immune system suppressant has various side effects. Crocin, a xanthine derivative plant, has many therapeutic benefits. This study was planned to assess the effect of crocin on renal toxicity of MTX in a rat model. Methods Forty eight rats were divided randomly into eight groups (n = 6), which received normal saline, MTX, crocin, and MTX + crocin for 28 days intraperitoneally. The levels of oxidative stress in kidney and blood serum were measured, and the kidney was analyzed histologically. Results MTX caused an enhancement in the levels of thiobarbituric acid reactive substances and biochemical marker (creatinine and BUN). Besides, a significant decrease was observed in tissue parameters and antioxidant capacity compared to the normal control group (p < 0.001). The crocin and crocin + MTX decreased the biochemical markers, the levels of thiobarbituric acid reactive species, and tissue parameters considerably at entire dose (12.5, 25, and 50 mg/kg) and enhanced the antioxidant capacity levels compared to the MTX group (p < 0.001). Conclusion Administration of crocin improves the damage caused by MTX in rats. The crocin by the establishment of balance in the levels of antioxidant prevents the damage to the renal cell membrane, and subsequently the renal damage repairs.

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract.

Abstract: There are few studies about the pharmacokinetics of the low-molecular mass carotenoids crocetin or crocin isomers from saffron (Crocus sativus L.). None has been performed with a galenic preparation of a standardised saffron extract. The aim of the present research work was to study the effect of in vitro digestion process on the main bioactive components of saffron extract tablets and the corresponding pharmacokinetic parameters in humans. Pharmacokinetics were calculated collecting blood samples every 30 min during the first 3 h and at 24 h after administration of two different concentrations (56 and 84 mg of the saffron extract) to 13 healthy human volunteers. Additionally, an in vitro digestion process was performed in order to determine the bioaccessibility of saffron main bioactive compounds. Identification and quantification analysis were performed by HPLC-PAD/MS. Digestion resulted in 40% of bioaccesibility for crocin isomers, whereas, safranal content followed an opposite trend increasing about 2 folds its initial concentration after the digestion process. Crocetin in plasma was detected in a maximum concentration (Cmax) in blood between 60 and 90 min after oral consumption with dose-dependent response kinetics, showing that crocin isomers from galenic preparation of saffron extract are rapidly transformed into crocetin. The results showed that this tested galenic form is an efficient way to administer a saffron extract, since the observed crocetin Cmax was similar and more quickly bioavailable than those obtained by other studies with much higher concentrations of crocetin.

Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage

Abstract: Pancreatic cancer is one of the fatal causes of global cancer-related deaths Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2 It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38 Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer

The effect of crocin supplementation on glycemic control, insulin resistance and active AMPK levels in patients with type 2 diabetes: a pilot study

Abstract: Crocin as a carotenoid exerts anti-oxidant, anti-inflammatory, anti-cancer, neuroprotective and cardioprotective effects. Besides, the increasing prevalence of diabetes mellitus and its allied complications, and also patients' desire to use natural products for treating their diseases, led to the design of this study to evaluate the efficacy of crocin on glycemic control, insulin resistance and active adenosine monophosphate-activated protein kinase (AMPK) levels in patients with type-2 diabetes (T2D). In this clinical trial with a parallel-group design, 50 patients with T2D received either 15-mg crocin or placebo, twice daily, for 12 weeks. Anthropometric measurements, dietary intake, physical activity, blood pressure, glucose homeostasis parameters, active form of AMPK were assessed at the beginning and at the end of the study. Compared with the placebo group, crocin improved fasting glucose level (P = 0.015), hemoglobin A1c (P = 0.045), plasma insulin level (P = 0.046), insulin resistance (P = 0.001), and insulin sensitivity (P = 0.001). Based on the within group analysis, crocin led to significant improvement in plasma levels of glucose, insulin, hemoglobin A1c, systolic blood pressure, insulin resistance and insulin sensitivity. The active form of AMPK did not change within and between groups after intervention. The findings indicate that crocin supplementation can improve glycemic control and insulin resistance in patients with T2D. Further studies are needed to confirm these findings. Trial Registration This study has been registered at Clinicaltrial.gov with registration number NCT04163757

Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway.

Abstract: Depression is a common non-motor symptom in patients with Parkinson's disease (PD) and difficult to treat. Crocin is a natural multipotential neuroprotective compound that has been shown to elicit antidepressant activity and is promising for the therapy of neuropsychological diseases. Here, we investigated the therapeutic effect of crocin in a mouse model of Parkinson's disease depression (PDD) and clarified the underlying mechanism. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute mouse model of PD, and found that around 60% of the model mice showed depression-like behavior, using the forced swimming test (FST). A regime of 10-day treatment of crocin alleviated the PDD symptoms. The crocin reduced the structural damage in soma volume and axon length of neurons and inhibited their spontaneous discharge in dopaminergic (DA) neurons in the ventral tegmental area (VTA). Notably, the MPTP-treated mice showed the decrease in the critical signaling for synaptic plasticity, including the proteins of PSD-95, synapsin-1, and GluR-1, in the medial prefrontal cortex (mPFC) where it receives efferent from VTA and regulates depression-like behavior. However, crocin treatment rescued the defect of the mammalian target of rapamycin (mTOR) signaling in PDD mice. Furthermore, the antidepressant action of crocin was blunted after blockade of mTOR signaling with the antagonist rapamycin. In conclusion, our study demonstrated that crocin protected the DA projection neurons in the VTA through activating mTOR, which subsequently improved the neural synaptic plasticity of mPFC, and ameliorated depression-like behavior in PD mice.

Crocin, an active constituent of Crocus sativus ameliorates cerulein induced pancreatic inflammation and oxidative stress.

Abstract: Acute pancreatitis (AP) is a disorder of the pancreas marked by profound inflammation and oxidative stress. Phytoconstituents presents an important toolbox of preventive strategies to combat inflammatory disorders. To this end, we selected the active constituent of Crocus sativus, crocin for evaluation against cerulein-induced AP, owing to its promising antiinflammatory activity in acute as well as chronic inflammatory conditions. The animals were randomly divided into five groups comprising of normal control, cerulein control, crocin low dose (30 mg/kg), crocin high dose (100 mg/kg), and crocin control (100 mg/kg). Various biochemical parameters and the levels of inflammatory cytokines and p65-NFκB were measured. The mechanism was investigated by histology and immunohistochemistry. We found that crocin significantly reduced the pancreatic edema, amylase, and lipase levels. It abrogated the oxidative stress incurred by cerulein challenge. We found that crocin modulated the pancreatic inflammatory cytokine levels. Crocin perturbed the nuclear translocation of p65-NFκB. Crocin reverted the pancreatic histology associated with AP. Furthermore, it upregulated the expression of Nrf-2 and downregulated the expression of IL-6, TNF-α, nitrotyrosine, and NFκB. Cumulatively, these results indicate that crocin has promising potential to prevent cerulein induced AP and regular intake of saffron can prove beneficial for the pancreatic health.

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation.

Abstract: At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/β-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/β-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.

The Hypoglycemic and Renal Protection Properties of Crocin via Oxidative Stress-Regulated NF-κB Signaling in db/db Mice.

Abstract: 1) Background: As the main ingredient of Crocus sativus L. (Iridaceae) extract, crocin- I (CR) has been reported to show various pharmacological activities. The aim of this study was to investigate the hypoglycemic and renal protection properties of CR in db/db mice; 2) Methods: Eight-week-old db/db mice were treated with metformin (Met) (100 mg/kg) and CR (50 mg/kg) for eight weeks; 3) Results: CR treatment showed hypoglycemic functions indicated by reduced bodyweight, food and water intake, plasma glucose, and serum levels of glycated hemoglobin A1c. Additionally, the CR group showed increased serum levels of insulin and pyruvate kinase, hypolipidemic functions indicated by the suppressed levels of total cholesterol and triglyceride, and enhanced levels of high-density lipoprotein cholesterol, which are also indicators of hypoglycemic functions. The renal protection function of CR was demonstrated by its protection of renal structures and its regulation of potential indicators of nephropathy. The anti-oxidation and anti-inflammation effects of CR were verified by enzyme-linked immunosorbent assay. In the kidneys of db/db mice, CR decreased the expression of phospho-IκBα and phospho-nuclear factor-κB (NF-κB), whereas it enhanced the expression of nuclear respiratory factor 2, manganese superoxide dismutase 1, heme oxygenase-1 and catalase; 4) Conclusions: The anti-diabetic and anti-diabetic nephritic effects of CR was related to its modulation of oxidative stress-mediated NF-κB signaling.