Role Of Crocin Research Articles

Effect of Crocin on Pituitary-Testicle Hormonal Axis in Alloxan-Induced Diabetic Male Rats

Background and Objectives Diabetes mellitus is a metabolic disease which causes disorders in the reproductive system. Recent studies have revealed that the main components of saffron like crocin and safranal have several physiological effects on different biological systems. Given the role of crocin in the modulation of antioxidant defense system, this study aimed to determine the effect of crocin on pituitary-testicle hormonal axis in alloxan-induced diabetic male rats. Subjects and Methods In this experimental study, 28 Wistar male rats were allocated into 4 equal groups: control, diabetic control, and two diabetic groups treated with crocin at two concentrations. Induction of diabetes in the diabetic control and the diabetic groups treated with crocin was done by an intraperitoneal injection of 240 mg/kg alloxan. Crocin at concentrations of 50 and 100 mg/kg [0.5 ml] was intraperitoneally injected into the two diabetic groups for 25 days. Saline solution [0.5 ml] was injected into the animals in the control and diabetic control groups for 25 days. At the end of the treatment period, serum levels of LH, FSH, estrogen, testosterone and DHT were measured by ELISA. Statistical analysis was carried out using one-way ANOVA and Tukey post hoc test. P <0.05 was considered statistically significant. Results Compared with the diabetic control group, administration of crocin at concentrations of 50 and 100 mg/kg significantly increased serum levels of LH, FSH, estrogen, and DHT testosterone in a dose-dependent manner [p<0.05]. Conclusion The results show that by increasing the activity of pituitary-testicle hormonal axis, crocin improves hormonal disorders in diabetic rats.

Evaluation of Crocin as green corrosion inhibitor for aluminum in NaCl solution

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.

Crocin ameliorates peritoneal fibrosis in rat induced by peritoneal dialysis via Wnt5a/β-Catenin pathway

Peritoneal dialysis is used in the treatment of patients with kidney diseases. Long-term peritoneal dialysis could result in peritoneal fibrosis and recurrent peritonitis, thus leading to failure of ultrafiltration. Crocin is a bioactive carotenoid and isolated from stigma of Crocus sativus, and ameliorates pulmonary and myocardial fibrosis. The role of crocin in peritoneal fibrosis was assessed. Firstly, rats model with peritoneal dialysis was treated with 4.25% peritoneal dialysate. Results showed that injection with peritoneal dialysate induced obvious hyperplasia and increased thickness in peritoneum structure. Rats with peritoneal dialysis were injected with increasing concentrations of crocin at 10, 20, or 40 mg/kg. Crocin ameliorated the pathological changes in the peritoneum of peritoneal dialysate-induced rats. Secondly, crocin attenuated peritoneal dialysate-induced decrease of E-cadherin, increase of fibronectin, α-smooth muscle actin (α-SMA), and collagen I. Moreover, crocin enhanced ultrafiltration volume and reduced glucose transport in rats model with peritoneal dialysis. Thirdly, crocin also reduced levels of Interleukin (IL)-1β, Tumor Necrosis Factor-α (TNF –α), and IL-6 in peritoneal tissues of rats model with peritoneal dialysis. Lastly, protein expression of Wnt5a and β-Catenin in rats model with peritoneal dialysis were also downregulated by crocin. In conclusion, crocin exerted anti-inflammatory and anti-fibrotic effects on rats model with peritoneal dialysis through inactivation of Wnt5a/β-Catenin pathway.

A Review on the Usage of Main Secondary Metabolites of Crocus sativus in Cancer Treatments

Saffron is the world’s second most costly spice, with numerous advantages of culinary, cosmetics, pharmaceutical and medical fields. There is an inadequate awareness of how Crocus sativus L. (Family Iridaceae) which produces the spice saffron from the filaments that grow inside the flower, can possibly treat cancer. Since, cancers are regarded as a devastating disease in today's world, anticancer and antioxidant properties of secondary metabolites available in saffron will be highly invaluable. The present review focuses on investigating on the role of crocin, crocetin and safranal in cancer treatments, which are the main secondary metabolites of C. sativus, and evaluating the various methods of extracting, isolating and analysing them. The review conducted using subjective indexed journal articles that were published over the past ten years. Out of the available data, it found that crocin would be quite beneficial in healing cancer without revealing any adverse effects. Crocin showed immense potential in curing a wide range of cancer types, mainly prostate and lung cancers, by eliminating cancer cells through apoptosis and inhibiting tumour invasion. There were a limited number of researches conducted using crocetin and safranal. However, they will approve for cancer treatments shortly. Crocetin was widely employed as a chemo-preventive and anti-inflammatory medication for pancreatic and breast cancer treatments. It has recently been utilized only for treatments of few types of cancers. Only one publication recorded in the recent ten years, as the usage of safranal in cancer treatment, which was against leukaemia. Moreover, secondary metabolite analysis techniques including spectrophotometry and chromatography utilized effectively, whereas predominantly improved extraction techniques including ultrasound-assisted extraction, emulsion liquid membrane, high hydrostatic pressure extraction. The analysis affirmed that, microwave[1]assisted extraction (80±1%) followed by low-pressure liquid chromatography (99.04±0.01%) showed optimum recovery of crocin. Whereas for safranal, microwave-assisted extraction (15.9±0.1%) and ultraviolet (UV) spectrophotometry preferred methods. The analysed data will be useful for future studies that focus on the analysis of saffron secondary metabolites and potentiality in cancer treatments to provide the researchers with a wide range of alternatives for carrying out the processes of curing cancers.
 Keywords: Anticancer, Crocin, Crocetin, Safranal, Saffron

Impact of copper oxide nanoparticles on the cerebral cortex of adult male albino rats and the potential protective role of crocin

ABSTRACT The use of copper oxide nanoparticles (CUONPs) on a large-scale application is a reason for many health problems and morbidities involving most body tissues, particularly those of the nervous system. Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects, such as antioxidant, anticancer, and memory-improving activities. This study was conducted to elaborate the effects of CUONP exposureon the cerebellar cortical tissues of rats and explore the potential protecting role of crocin through biochemical, light microscopic, and ultrastructural examinations. Twenty four adult male albino rats were randomly divided into four equal groups: Group I (negative control); Group II (crocin-treated group; 30mg/kg body weight (BW) intraperitoneal (IP) crocin daily); Group III (CUONP-treatedgroup; 0.5-mg/kg BW IP CUONP daily); and Group IV (CUONP/crocin-treated group). After 14 days of the experiment, venous blood samples were collected to determine red blood cell (RBC), white blood cell (WBC), and hemoglobin (Hb) levels. Besides, serum malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured. Cerebellar tissue samples were examined under light and electron microscopy along with a histomorphological analysis. CUONPs induced oxidative/antioxidative imbalance as evidenced by a significant increase in serum MDA levels and decreased GPx and TAC activities. CUONPs caused a significant decrease in RBC and Hb levels and an increase in WBC count. Histopathological alterations in the cerebellar cortex were observed. The administration of crocin showed some protection against the toxic effects of CUONPs. Crocin is suggested to have a mitigating role on oxidative stress and structure alterations in the cerebellar tissues induced by CUONPs.

Crocin inhibits the activation of mouse hepatic stellate cells via the lnc-LFAR1/MTF-1/GDNF pathway

ABSTRACT Crocin is the main monomer of saffron, which is a momentous component of traditional Chinese medicine Lang Qing A Ta. Here, we tried to probe into the role of crocin in liver fibrosis. Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues. After hepatic stellate cells (HSCs) were isolated from liver tissues, lnc-LFAR1, MTF-1, GDNF, and α-SMA expressions were detected by qRT-PCR and western blot. Immunohistochemistry and immunofluorescence were used to detect α-SMA expression. Chromatin immunoprecipitation was used to analyze the binding of MTF-1 to the GDNF promoter. Moreover, the dual-luciferase reporter gene, RNA pull-down, and RNA immunoprecipitation were used to clarify the interaction between MTF-1 and GDNF, lnc-LFAR1 and MTF-1. The degree of liver fibrosis was more severe in the mice from the liver fibrosis model, while the liver fibrosis was alleviated by the injection of crocin. lnc-LFAR1, GDNF, and α-SMA were up-regulated, and MTF-1 was down-regulated in liver fibrosis tissues and cells, while these trends were reversed after the injection of crocin. Besides, lnc-LFAR1 negatively regulated MTF-1 expression, and positively regulated GDNF and α-SMA expressions, and MTF-1 was enriched in the promoter region of GDNF. Furthermore, the cellular direct interactions between MTF-1 and GDNF, lnc-LFAR1 and MTF-1 were verified. In vivo experiments confirmed the relief of crocin on liver fibrosis. Our research expounded that crocin restrained the activation of HSCs through the lnc-LFAR1/MTF-1/GDNF axis, thereby ameliorating liver fibrosis.

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

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.

Crocin may be useful to prevent or treatment of alcohol induced neurodegeneration and neurobehavioral sequels via modulation of CREB/BDNF and Akt/GSK signaling pathway

The neurodegeneration and neurobehavioral consequences of alcohol are serious and offering therapeutic approaches for management of these types of neurodegeneration is one of the main concerns of researchers in this manner. Alcohol-stimulated oxidative stress, apoptosis and inflammation, with modulation of involved signaling pathway in neuroprotection, was reported previously. Neuroprotective strategy for management of alcohol induced neurodegeneration through a new generation neuroprotective agent and based on modulation of some neuroprotective signaling pathway such as CREB/BDNF and Akt/GSK has always been superior to any other therapeutic interventions. Therefore, the introduction and development of potential new neuroprotective properties and clarification of their effects on major cell signaling such as CREB/BDNF and Akt/GSK is necessitated. During recent years, using new neuroprotective compounds with therapeutic probability for treatment of alcohol induced neuro-biochemical and neuro-behavioral malicious effects have been amazingly increased. Many previous studies have reported the neuroprotective roles of crocin (major active component of saffron) in multiple neurodegenerative events and diseases in animal model. But the role of crocin neuroprotective effects against alcohol induced neurodegeneration and neurobehavioral sequels and also role of CREB/BDNF and Akt/GSK in this manner remain unclear. Hence we hypothesized that by using crocin in alcohol dependent subject it would provide neuroprotection against alcohol induced neurodegeneration and neurobehavioral and probably can manage sequels of alcohol abuses. Also we hypothesized that crocin, via intonation of CREB/BDNF and Akt/GSK signaling pathway, can inhibit alcohol induced neurodegeneration. In this article, we tried to discuss our hypothesis regarding the possible role of crocin, as a potent neuroprotective agent, and also role of Akt/GSK and CREB/BDNF signaling pathway in treatment of alcohol induced neurodegeneration and neurobehavioral through its anti-inflammatory,anti-apoptotic, anti-oxidative stress and cognitive enhancer.

The role of Crocin in an acrylamide-induced neurotoxicity model in Wistar rats

Aim: The changes in rat brain tissues treated with Crocin (Cr) as a protective agent in an acrylamide (AA) neurotoxicity model were investigated.Material and Methods: The present with of the experimental animal ethics committee at Inonu University, Faculty of Medicine (2016 / A-59). Forty male rats were randomly divided into 4 groups with study was conducted the approval equal number of rats (10): Control, Cr, AA, Cr + AA Groups. Malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Oxidative stress index (OSI), superoxide dismutase (SOD), catalase (CAT) and protein values were examined in the brain tissues.Results: MDA, TOS and OSI levels increased in brain tissues of AA administered rats when compared to the other groups, while the GSH, TAS, SOD and CAT levels decreased in the group (p 0.05). GSH, TAS, SOD and CAT levels increased, but MDA, TOS and OSI levels decreased in the AA + Cr administered group when compared to the AA group (p 0.05). It was observed that oral AA administration altered the antioxidant/oxidant balance favoring the oxidants in male rat brain tissues, leading to oxidative stress induced neurotoxicity, while Cr administration reestablished the normal antioxidant/oxidant balance, preventing the oxidative stress induced neurotoxicity via detoxification. Conclusion: The present study concluded that the administered Cr dose was sufficient to prevent neurotoxicity and we recommend that adequate amounts of Cr should be consumed to prevent AA-induced toxicity and improve antioxidant capacity.

Role of Dietary Crocin in In Vivo Melanoma Tumor Remission

Background:Melanoma is a deadly form of malignancy. Early diagnosis might pave the way to cure but its aggressive nature leads to rapid dissemination and colonization of distant organs. Dietary herbs may play a significant role in prevention of cancer. In this study, we tested anti-tumor efficacy of the Crocus sativus derived active constituent crocin, it is well established to have anti-cancer properties in different cancer models by our group and other groups. Notably, crocin is reported to exert anti-proliferative effect on melanoma cells (B16F10) in vitro. However, roles of crocin on in vivo melanoma tumor remission have not yet been reported to our knowledge.Materials and Methods:Melanoma tumor model was established by transplanting B16F10 (5 X 105) cells into C57BL/6 mice, which were then observed for tumor development and once the tumor volume reached 6 mm, mice were divided into (Group I: tumor-bearing animals treated with normal saline and Group II: counterparts treated with crocin at 2 mg/kg body weight for 21 days).. Tumor remission and tumor growth related parameters such as tumor silent period (TSP), tumor volume doubling time (VDT), growth delay (GD), and mean survival time (MST) were determined. In addition, serum protein profiles were analyzed.Results:The 21 days crocin treatment significantly reduced the tumor burden in mice, extending the mean survival time significantly as compared to control. Crocin treatment also significantly increased the TGD and TSP and decreased VDT. Furthermore, while serum proteins such as albumin and globulin (alpha1, alpha2, beta, and gamma) were altered due to tumor burden, crocin treatment resulted in their levels near to normal at the end of the experimental period.Conclusion:Our study provided clear evidence that crocin may exhibit significant melanoma tumor remission properties by positively modulating tumor growth related parameters. In future, the molecular mechanisms of crocin action should be studied extensively in melanoma models before defining crocin-based melanoma drug formulations.