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Showing papers on "Crocin published in 2017"


Journal ArticleDOI
TL;DR: The biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action are described.
Abstract: Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation‐related proteins, retinoid‐like receptors, antioxidant response element, nuclear receptors, AP‐1 transcriptional complex, the Wnt/β‐catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B‐ and T‐lymphocytes, the activity of macrophages and cytotoxic T‐cells, effector T‐cell function and the production of cytokines. Recently, the beneficial effects of carotenoid‐rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β‐carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time‐ and dose‐dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action.

421 citations


Journal ArticleDOI
TL;DR: It is demonstrated that crocin exhibits multifunctional protective activities in the brain and could be a promising agent applied as a supplement or drug for prevention or treatment of AD.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia, in which the death of brain cells causes memory loss and cognitive decline. Several factors are thought to play roles in the development and course of AD. Existing medical therapies only modestly alleviate and delay cognitive symptoms. Current research has been focused on developing antibodies to remove the aggregates of amyloid-β (Aβ) and tau protein. This approach has achieved removal of Aβ; however, no cognitive improvement in AD patients has been reported. The biological properties of saffron, the dry stigma of the plant Crocus sativus L., and particularly its main constituent crocin, have been studied extensively for many conditions including dementia and traumatic brain injury. Crocin is a unique antioxidant because it is a water-soluble carotenoid. Crocin has shown potential to improve learning and memory as well as protect brain cells. A search of the studies on saffron and crocin that have been published in recent years for their impac...

107 citations


Journal ArticleDOI
TL;DR: It is found that crocin prevented the oxidative stress and pro-inflammatory response induced by HG-FFA co-treatment, and it is revealed that PI3K/Akt signaling plays a significant role in blocking oxidative stress, suppressing the pro- inflammatory response, and maintaining the neuroprotective effects of crocin.
Abstract: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus that is closely associated with the degeneration and loss of retinal ganglion cells (RGCs) caused by diabetic microangiopathy and subsequent oxidative stress and an inflammatory response. Microglial cells are classed as neurogliocytes and play a significant role in neurodegenerative diseases. Over-activated microglial cells may cause neurotoxicity and induce the death and apoptosis of RGCs. Crocin is one of the two most pharmacologically bioactive constituents in saffron. In the present study, we focused on the role of microglial cells in DR, suggesting that DR may cause the over-activation of microglial cells and induce oxidative stress and the release of pro-inflammatory factors. Microglial cells BV-2 and N9 were cultured, and high-glucose (HG) and free fatty acid (FFA) were used to simulate diabetes. The results showed that HG-FFA co-treatment caused the up-regulated expression of CD11b and Iba-1, indicating that BV-2 and N9 cells were over-activated. Moreover, oxidative stress markers and pro-inflammatory factors were significantly enhanced by HG-FFA treatment. We found that crocin prevented the oxidative stress and pro-inflammatory response induced by HG-FFA co-treatment. Moreover, using the PI3K/Akt inhibitor LY294002, we revealed that PI3K/Akt signaling plays a significant role in blocking oxidative stress, suppressing the pro-inflammatory response, and maintaining the neuroprotective effects of crocin. In total, these results provide a new insight into DR and DR-induced oxidative stress and the inflammatory response, which provide a potential therapeutic target for neuronal damage, vision loss, and other DR-induced complications.

87 citations


Journal ArticleDOI
TL;DR: This study reviewed anticancer effects of crocin and its underlying molecular mechanisms and suggested that it is one of the most effective cancer therapeutic constituents of saffron stigma.
Abstract: Objectives Crocin is derived from dried stigmas of Crocus sativus L. (saffron). It has long been used to prevent and treat various diseases. Although crocin is suggested as one of the most effective cancer therapeutic constituents of saffron stigma, its exact molecular mechanisms are not fully understood. In this study, we reviewed anticancer effects of crocin and its underlying molecular mechanisms. Key findings While several mechanisms may account for the antitumour activity of crocin, alteration of expression/activity of the genes and also epigenetic changes may be considered as necessary phenomena. These alternations may lead to inhibition of cancer cells' proliferation or/and induction of apoptosis through various mechanism including inhibition of synthesis of DNA and RNA, interaction with cellular topoisomerase, suppression of the telomerase activity and active STAT3, and targeting of microtubules. Moreover, this carotenoid could reverse the epithelial–mesenchymal transition and inhibit metastasis. Conclusions Knowing molecular mechanisms of antitumoral agents could guide us to choose the best chemotherapeutic compound especially for targeted therapy and also provide insights about possible side effects.

84 citations


Journal ArticleDOI
TL;DR: Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations, and classified information about the toxic effects of saFFron and its constituents in various exposure conditions including acute, under-acute, sub-chronic and chronic studies are provided.
Abstract: Saffron (Crocus sativus L.) has been considered as a medicinal plant since ancient times and also widely used as food additive for its color, taste and odor. The pharmacological properties of saffron and its main constituents, crocin and safranal have been evaluated using different in vivo and in vitro models. Additionally, other lines of studies have found toxicological effects of saffron. However, a comprehensive review that covers all aspects of its toxicity has not been published yet. The current study provides classified information about the toxic effects of saffron and its constituents in various exposure conditions including acute, sub-acute, sub-chronic and chronic studies. Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.

83 citations


Journal ArticleDOI
TL;DR: Experimental reports collected in this study strongly indicate that nanoparticles loaded with crocin could be the prospective candidates for the future anti-cancer therapeutics that deserve additional investigations.

80 citations


Journal ArticleDOI
TL;DR: The findings suggest that crocin possesses hepatoprotective effects against BPA-induced liver toxicity by enhancing the antioxidative defense system and regulation of important signaling pathway activities and miR-122 expression.

71 citations


Journal ArticleDOI
TL;DR: Developing an effective method for treatment of liver cancer using magnetite nanoparticles coated with crocin, the main active component of saffron, and finding crocin-coated MNPs are more effective than free corcin forreatment of liver precancerous lesions in mice is developed.
Abstract: Despite considerable advances in understanding hepatocellular carcinoma, it is one of the common and deadliest cancers worldwide. Hence, increasing efforts are needed for early diagnosis and effective treatments. Saffron has been recently found to inhibit growth of liver cancer in rats. The aim of this study was to develop an effective method for treatment of liver cancer using magnetite nanoparticles (MNPs) coated with crocin, the main active component of saffron. MNPs were prepared and initially coated with dextran and a cross-linker to enhance conjugation of crocin using a modified coprecipitation method. Cultured HepG2 cells and diethylnitrosamine-injected mice were treated with corcin-coated MNPs and analyzed using cell proliferation assay and immunohistochemical analysis, respectively. Treatment of HepG2 cells with crocin-coated MNPs led to a significant inhibition of their growth as compared to control or those treated with free crocin or uncoated MNPs. Histological examinations of the livers of diethylnitrosamine-injected mice revealed several precancerous changes: multiple proliferative hepatic foci, hyper- or dysplastic transformations of bile ducts/ductules, and nuclear atypia associated with polyploidy, karyomegaly, and vacuolation. Immunohistochemistry using antibodies specific for cell proliferation (Ki-67) and apoptosis (M30-CytoDEATH and Bcl-2) revealed their upregulation during development of precancerous lesions. Using antibodies specific for inflammation (cyclooxygenase-2), oxidative stress (glutathione) and angiogenesis (vascular endothelial growth factor) indicated the involvement of multiple signaling pathways in the development of precancerous lesions. Treatment with crocin-coated MNPs was associated with regression of precancerous lesions, significant upregulation of apoptotic cells and downregulation of Bcl-2 labeling and markers of cell proliferation, inflammation, oxidative stress and angiogenesis. In conclusion, crocin-coated MNPs are more effective than free corcin for treatment of liver precancerous lesions in mice. These findings will help to develop new modalities for early detection and treatment of liver precancerous lesions.

62 citations


Journal ArticleDOI
TL;DR: There was a significant improvement in many morphological and physiological traits in endophyte treated Crocus plants including total biomass and size of corms, stigma biomass, number of apical sprouting buds, and number of adventitious roots.
Abstract: Crocus sativus is the only plant species which produces apocarotenoids like crocin, picrocrocin and safranal in significant amounts. These compounds impart organoleptic properties to saffron (dried stigmas of Crocus flower) making it world’s costliest spice. Crocus apocarotenoids have tremendous medicinal properties as well. Effect of endophytes on Crocus apocarotenoid production and the molecular mechanism involved has not been reported so far. Here we studied the effect of an oleaginous fungal endophyte, Mortierella alpina CS10E4 on Crocus growth, apocarotenoid metabolism and tolerance to corm rot disease. The results demonstrated that there was a significant improvement in many morphological and physiological traits in endophyte treated Crocus plants including total biomass and size of corms, stigma biomass, number of apical sprouting buds, and number of adventitious roots. The endophyte also shifted metabolic flux towards enhanced production of apocarotenoids by modulating the expression of key pathway genes. Further, M. alpina CS10E4 enhanced tolerance to corm rot disease by releasing arachidonic acid which acts as conserved defense signal and induces jasmonic acid production in endophyte treated Crocus corms. This is first report on effect of a fungal endophyte on Crocus apocarotenoid metabolism and stress tolerance.

61 citations


Journal ArticleDOI
TL;DR: In this paper, the antioxidant potential of three natural origin drugs, namely crocin, kaempferol and podophyllotoxin, was evaluated by chemical, biochemical and electrochemical assays.

59 citations


Journal ArticleDOI
TL;DR: Crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules by disrupting the microtubule network.
Abstract: Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin. Electron microscopic analysis showed that crocin inhibited microtubule assembly while it induced aggregation of tubulin at higher concentrations. Crocin co-eluted with tubulin suggesting that it binds to tubulin. Vinblastine inhibited the binding of crocin to tubulin while podophyllotoxin did not inhibit the crocin binding indicating that crocin binds at the vinblastine site on tubulin. The results suggested that crocin inhibited cell proliferation mainly by disrupting the microtubule network.

Journal ArticleDOI
TL;DR: It was demonstrated that crocin treatment removed acrylamide induced liver damage due to the strong antioxidant properties of crocin.

Journal ArticleDOI
TL;DR: The positive effect of Crocus sativus against AD is supported by reducing Aβ pathological manifestations by boosting BBB clearance, enzymatic degradation and ApoE clearance pathway.
Abstract: Crocus sativus, commonly known as saffron or Kesar, is used in Ayurveda and other folk medicines for various purposes as an aphrodisiac, antispasmodic, and expectorant. Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer’s disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. The effect of Crocus sativus extract on Aβ load and related toxicity was evaluated. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aβ load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aβ load could be explained, at least in part, by Crocus sativus extract effect to enha...

Journal ArticleDOI
TL;DR: It is demonstrated that crocin protected the liver against IR injury through increasing the activity of antioxidant enzymes, improving serum levels of liver enzymes, downregulating miR-122,MiR-34a, and p53, and upregulating Nrf2 expression.
Abstract: Background. Liver ischemia-reperfusion (IR) injury is one of the chief etiologies of tissue damage during liver transplantation, hypovolemic shock, and so forth. This study aimed to evaluate hepatoprotective effect of crocin on IR injury and on microRNAs (miR-122 and miR-34a) expression. Materials and Methods. 32 rats were randomly divided into four groups: sham, IR, crocin pretreatment (Cr), and crocin pretreatment + IR (Cr + IR) groups. In sham and Cr groups, animals were given normal saline (N/S) and Cr (200 mg/Kg) for 7 consecutive days, respectively, and laparotomy without inducing IR was done. In IR and Cr + IR groups, N/S and Cr were given for 7 consecutive days and rats underwent a partial (70%) ischemia for 45 min/reperfusion for 60 min. Blood and tissue samples were taken for biochemical, molecular, and histopathological examinations. Results. The results showed decreased levels of antioxidants activity and increased levels of liver enzymes improved by crocin. The expression of miR-122, miR-34a, and p53 decreased, while Nrf2 increased by crocin. Crocin ameliorated histopathological changes. Conclusion. The results demonstrated that crocin protected the liver against IR injury through increasing the activity of antioxidant enzymes, improving serum levels of liver enzymes, downregulating miR-122, miR-34a, and p53, and upregulating Nrf2 expression.

Journal ArticleDOI
TL;DR: This review is aimed to provide a brief overview on the anti-tumor potential of saffron focusing on the molecular mechanism involved.
Abstract: Cancer is a disorder which has noted a significant rise in incidence worldwide and continues to be the largest cause of mortality. It has a dramatic impact on human life expectancy and quality of life in spite of the increase in technology and the treatments available for cancer patients. These new therapeutic options being chemotherapy, radiotherapy, photolytic therapy and catalytic therapy are known to have many adverse reactions and also no better positive outcomes than before. Hence, research is now focused more on utilizing the vast repertoire of traditional medicinal knowledge i.e. the use of flora for treatment of cancer rather than the use of chemicals. One such herb is the Crocus sativus L., commonly known as Saffron, rich in carotenoids - crocin, crocetin and safranal. Various studies have been carried out over the past few years to confirm the anti-cancer properties of saffron, both in vivo using animal models and in vitro using human malignant cell lines on various types of cancers with positive results. The proposed mechanism of actions has also been worked upon. This review is aimed to provide a brief overview on the anti-tumor potential of saffron focusing on the molecular mechanism involved.

Journal ArticleDOI
TL;DR: In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associated with down‐regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis.

Journal ArticleDOI
TL;DR: It is suggested that beneficial effects of crocin on streptozotocin-induced memory dysfunction may be attributed to its antidiabetic and antioxidant activity, which could find clinical use in treating cognitive dysfunction in diabetics.

Journal ArticleDOI
Sutong Li, Xiaoxia Liu, Jie Lei, Junle Yang, Puxun Tian1, Yi Gao 
TL;DR: A protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB is demonstrated.
Abstract: Background/Aims: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB. Methods: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria. Cells were incubated with 15 or 25 mM D-glucose to mimic diabetic conditions. The expression of Wilms tumor 1 (WT-1) and synaptopodin was evaluated to identify differentiated podocytes, and the expression of nephrin, podocin, and CD2ap was measured as markers of slit diaphragms, the main structures within the glomerular filtration barrier. Results: The high-glucose conditions led to reduced nephrin, podocin, and CD2ap expression, which was prevented by pretreatment with crocin. The oxidative stress and pro-inflammatory response of podocytes associated with DN induced by high glucose were also reduced by crocin pretreatment. Phosphorylated IκBα (p-IκBα) expression induced by high glucose was also significantly decreased by crocin pretreatment. Moreover, pyrrolidine dithiocarbamate, a NF-κB inhibitor, pyrrolidine dithio carbamate, augmented the protective effects of crocin. Conclusion: Our results demonstrate a protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB. This study presents a potential therapy for DN and contributes to the understanding of the mechanism underlying DN.

Journal ArticleDOI
TL;DR: Crocin and crocetin in rat plasma were simultaneously analysed using ultra-performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS), and it was shown that crocin transformed into croCetin quickly in the gastrointestinal tract, and cro cetin was 56-81 fold higher exposed in rat Plasma than crocin after oral administration of crocin.

Journal Article
TL;DR: Although crocin supplements increased the serum cholesteryl ester transfer protein in patients with metabolic syndrome, this change was not significant between treatment and placebo groups.
Abstract: BACKGROUND: Metabolic syndrome is defined by insulin resistance and a clustering of other cardiovascular risk factors. Crocin is a carotenoid derived from the stigmas of the saffron flower and had previously been shown to affect lipid profile. However, the mechanism for this function is not well understood. The present trial aimed to investigate the possible effect of crocin on plasma levels of cholesteryl ester transfer protein and lipid profile in individuals with metabolic syndrome. METHODS: This was a randomized, double-blind, placebo-controlled, clinical trial consisting of an 8-week treatment with crocin, or placebo tablets between April and June 2014, in the Nutrition Clinic of Ghaem Teaching Hospital, Mashhad, Iran. Participants were randomly assigned to take a 30 mg/day crocin ( n = 22) in the intervention group or placebo ( n = 22) in the control group. Anthropometric, hematological and biochemical parameters were measured and recorded during pre and post-trea t ment periods. RESULTS: Whilst plasma cholesteryl ester transfer protein was increased in the group taking the crocin tablet by 27.81% during the trial period (P = 0.013), the difference between the crocin and placebo groups was not significant (P = 0.116). Moreover, the percent changes in cholesterol (P = 0.702), triglyceride (P = 0.080), low-density lipoprotein (LDL) (P = 0.986), high-density lipoprotein (HDL) (P = 0.687) and fasting blood glucose (P = 0.614) did not differ significantly between intervention and control groups. CONCLUSION: Although crocin supplements increased the serum cholesteryl ester transfer protein in patients with metabolic syndrome, this change was not significant between treatment and placebo groups.

Journal ArticleDOI
TL;DR: This work studied the process of chromoplast differentiation in saffron throughout stigma development by means of transmission electron microscopy and provided an overview of a massive transport of crocins to the vacuole in the later developmental stages, when electron dense drops of a much greater size than plastoglobules were observed in the Chromoplast.
Abstract: Crocins, the glucosides of crocetin, are present at high concentrations in saffron stigmas and accumulate in the vacuole. However, the biogenesis of the saffron chromoplast, the changes during the development of the stigma and the transport of crocins to the vacuole, are processes that remain poorly understood. We studied the process of chromoplast differentiation in saffron throughout stigma development by means of transmission electron microscopy. Our results provided an overview of a massive transport of crocins to the vacuole in the later developmental stages, when electron dense drops of a much greater size than plastoglobules (here defined "crocinoplast") were observed in the chromoplast, connected to the vacuole with a subsequent transfer of these large globules inside the vacuole. A proteome analysis of chromoplasts from saffron stigma allowed the identification of several well-known plastid proteins and new candidates involved in crocetin metabolism. Furthermore, expressions throughout five developmental stages of candidate genes responsible for carotenoid and apocarotenoid biogenesis, crocins transport to the vacuole and starch metabolism were analyzed. Correlation matrices and networks were exploited to identify a series of transcripts highly associated to crocetin (such as 1-Deoxy-d-xylulose 5-phosphate synthase (DXS), 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), carotenoid isomerase (CRTISO), Crocetin glucosyltransferase 2 (UGT2), etc.) and crocin (e.g., ζ-carotene desaturase (ZDS) and plastid-lipid-associated proteins (PLAP2)) accumulation; in addition, candidate aldehyde dehydrogenase (ADH) genes were highlighted.

Journal ArticleDOI
TL;DR: The present study demonstrated the anti-proliferative and apoptotic activities of crocin against both sensitive and resistant cervical cancer cells that may benefit cervical cancer treatment as an adjuvant agent to decrease chemoresistance and increase the efficiency of therapy.

Journal ArticleDOI
TL;DR: It is concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ‐induced kindling development and improving cognitive functions and the effect was found to be due to suppression of seizure‐induced ROS generation and its linked NF‐κB pathway‐associated neuronal damage.
Abstract: Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. This study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)-induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed a marked reduction in severity of PTZ-induced seizures. There was an increase in novel object preference index and discrimination ratio in the crocin-treated groups in the novel object recognition test. Its treatment also increased percentage spontaneous alternations in T-maze test at all the tested doses. Histopathological examination by Nissl staining showed a reduction in dark neurons in the hippocampal pyramidal layer of crocin-treated animals in contrast to vehicle control, indicating a decrease in neuronal damage. Biochemical estimations showed a significant increase in superoxide dismutase activity and reduced reactive oxygen species (ROS) in the hippocampus of crocin-treated animals. Immunohistochemistry results revealed attenuation in the levels of nuclear factor-κB (NF-κB) and phosphorylated NF-κB in the hippocampal sections of crocin-treated animals. The results of this study concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ-induced kindling development and improving cognitive functions. The effect was found to be due to suppression of seizure-induced ROS generation and its linked NF-κB pathway-associated neuronal damage.

Journal ArticleDOI
TL;DR: It is highlighted that nanostructured lipid dispersions can protect the labile molecule crocin from degradation, control its skin diffusion and prolong antioxidant activity, therefore suggesting the suitability of nanostructure lipid dispersion for crocin topical administration.

Journal ArticleDOI
TL;DR: The results of present study regarding anti-obesity feature of SAE and crocin in patients with CAD was promising, however the SAE was better in appetite suppressing, dietary intake and central obesity reduction.
Abstract: Introduction: Central obesity is an independent risk factor for coronary artery disease (CAD). It can increase cardio-metabolic risks through hypertension, hyperlipidemia and insulin resistance. Saffron and its bioactive compounds (crocin and crocetin) can modify some of metabolic disorders through multiple mechanisms. The aim of this study was to assess the efficacy of saffron and crocin on lipid profile, appetite, dietary intakes, anthropometric indices and body composition in patients with CAD. Methods: This 8 weeks randomized, double-blind, and placebo-controlled trial was conducted on 84 patients with CAD between the ages of 40 and 65 years old. Participants were randomly divided into groups to receive a daily supplement of 30 mg saffron aqueous extract (SAE) or 30 mg crocin or placebo. Appetite, dietary intake, anthropometry, body composition, biochemical analysis were assessed before and after the study. Results: In SAE and crocin group, anthropometric and some body composition variables revealed a pattern of improvement after intervention. Decrease in body mass index (BMI), waist circumference and fat mass values in SAE group was significantly more than crocin group (P < 0.001). There was no significant difference at the end of study in lipid profile parameters. Both SAE and crocin yielded significant decrease in energy and dietary intake mean values (P < 0.001 and P = 0.046), while it remained unchanged in the placebo group, also the appetite decreased significantly in SAE and crocin group (P < 0.001 and P = 0.029, respectively). Conclusion: The results of present study regarding anti-obesity feature of SAE and crocin in patients with CAD was promising. However the SAE was better in appetite suppressing, dietary intake and central obesity reduction.

Journal ArticleDOI
TL;DR: The findings suggest that crocin is able to enhance memory function in D-gal aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators (IL-1, TNF and NF-κB) formations and increase PI3K/Akt and Erk/MAPK pathways activity.
Abstract: Objective(s): The neurodegeneration and loss of memory function are common consequences of aging. Medicinal plants have potent protective effects against chronic neurodegenerative diseases. The aim of this study was to investigate the beneficial effects and molecular mechanisms of crocin on brain function in D-galactose (D-gal)-induced aging model in rats. Materials and Methods: Male Wistar rats weighing 220 ± 20 g were randomly divided into six groups: control, D-gal (400 mg/kg, SC), D-gal (400 mg/kg) plus crocin (7.5, 15, 30 mg/kg, IP) and crocin alone at dose of 30 mg/kg for 8 weeks. The neuroprotective effects of crocin were evaluated by Morris water maze, determination of malondialdehyde (MDA) levels and Western blot analysis. Results: Crocin significantly inhibited the neurotoxic effects of D-gal through improvement of spatial learning and memory functions as well as the reduction of MDA levels. It was also found that administration of crocin up-regulated pAkt/Akt and pErk/Erk ratio which were decreased by chronic D-gal treatment. In addition, the elevated level of carboxymethyl lysine (CML), as an advance glycation product (AGE), NF-κB p65, TNFα and IL1β significantly decreased in crocin treated rats compared to D-gal group. Conclusion: These findings suggest that crocin is able to enhance memory function in D-gal aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators (IL-1, TNF and NF-κB) formations and increase PI3K/Akt and Erk/MAPK pathways activity. Therefore, crocin can be considered as healthcare product to prevent age-related brain diseases such as Alzheimer.

Journal ArticleDOI
TL;DR: Ccin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6 and may exert potent anti-RA effects through inhibiting cytokine.
Abstract: This study is to determine the role and mechanism of crocin in rheumatoid arthritis (RA). Totally 60 Wistar SD rats were randomly divided into control group, RA model group, methotrexate group, crocin high dose, middle dose, and low dose groups. The paw swelling degree, arthritis score, thymus and spleen index, the mRNA and protein levels of iNOS, and the serum content of TNF-α, IL-1β, and IL-6 were evaluated. Crocin treatment significantly alleviated the paw swelling of RA rats. The arthritis score in crocin treatment groups was significantly lower than that in RA model group. Additionally, the thymus index, but not the spleen index, declined remarkably in crocin treatment groups than in RA model group. Besides, crocin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6. Crocin may exert potent anti-RA effects through inhibiting cytokine.

Journal ArticleDOI
TL;DR: The present study clearly demonstrated the anti-inflammatory, antioxidant, and protective effects of crocin, a main constituent of saffron, against renal damages resulted from I/R in rats.
Abstract: Objective(s): Crocus sativus (saffron) has been widely used in traditional medicine. It has also been found to possess many beneficial properties in modern medicine. The most important ingredients of saffron are crocin, crocetin, safranal, and picrocrocin. This study evaluated the protective effects of crocin against the inflammation, oxidative stress, and functional disturbances of the kidney induced by renal ischemia/reperfusion (I/R). Materials and Methods: Different doses of crocin (0, 100, 200, and 400 mg/kg) were administered intraperitoneally 30 min before I/R. The rats of the sham group were also injected with normal saline before the sham surgery. For induction of I/R, both renal artery and vein clamped for 30 min, bilaterally. The I/R-induced renal injuries were assessed by measuring leukocyte infiltration, intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-α) mRNA expression levels, malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels in the kidney tissue, and plasma creatinine and urea-nitrogen concentrations. Results: Except for the tissue level of FRAP which decreased, all other measured parameters increased following I/R induction. Pretreatment with all doses of crocin significantly reduced the severity of these disturbances (PP<0.001). In fact, while there was no significant differences between MDA and FRAP levels, plasma creatinine and urea-nitrogen concentrations of the crocin-treated animals and the sham group, crocin administration reduced leukocyte infiltration and ICAM-1 and TNF-α mRNA expression levels in a dose-dependent manner. Conclusion: The present study clearly demonstrated the anti-inflammatory, antioxidant, and protective effects of crocin, a main constituent of saffron, against renal damages resulted from I/R in rats.v

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TL;DR: Voluntary exercise and diet supplementation with crocin could have beneficial effects in prevention of cardiovascular disease and improve heart angiogenesis possibly through enhancement of MiR-126 and miR-210 expression.
Abstract: Background: Crocin is reported to have a wide range of biological activities such as cardiovascular protection Recent epidemiologic studies have shown that exercise reduces cardiovascular morbidity and mortality in the general population Objective: The aim of this study was to evaluate the effect of crocin and voluntary exercise on miR-126 and miR-210 expression levels and angiogenesis in the heart tissue Methods: Animals were divided into 4 groups: control, exercise, crocin, and exercise-crocin Animals received oral administration of crocin (50 []

Journal ArticleDOI
TL;DR: It is concluded that antidepressant activity of crocin might be partially mediated to CREB, and other factors rather than BDNF and VGF neuropeptides may alter following long term crocin treatment in the cerebellum.
Abstract: Antidepressant activity of crocin, saffron main component, has been established before. Based on previous study, it is suggested that elevation in the levels of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide could be considered as one probable molecular mechanisms involved in antidepressant activity of long term crocin administration in the rat hippocampus. In this study we further investigated whether the antidepressant activity of crocin in long term administration was associated with alteration in these factors in the rat cerebellum. Crocin (12.5, 25 and 50 mg/kg/day) and imipramine (10 mg/kg/day) were administered interaperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were dissected. BDNF, VGF, CREB, and phospho-CREB (P-CREB) protein and mRNA levels in the rat cerebellum were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the current study significant increases in mRNA and protein levels of VGF, CREB and (BDNF) in long term crocin treatment were not observed in the rat cerebellum. Although a slight increase was observed in protein level of P-CREB compared to normal saline, but it was not significant. It is concluded that antidepressant activity of crocin might be partially mediated to CREB. Moreover, other factors rather than BDNF and VGF neuropeptides may alter following long term crocin treatment in the cerebellum. To understand the precise mechanism of crocin antidepressant effects in the cerebellum, longer duration of crocin treatment in further studies is recommended.