Effect Of Saffron Aqueous Extract Research Articles

Effects of saffron aqueous extract on depression in male Wistar rats with chronic social defeat stress

Background: Depression, as a mental disorder, causes many complications in humans. Saffron has been suggested as one of the effective plants in treating various types of depression. The present study aims to assess the effect of the aqueous extract of saffron on depression caused by chronic social defeat stress (CSDS) in rats. Materials and Methods: To induce CSDS, male Wistar intruder rats (Weight= 220-230 g) were put in the cage of male Wistar resident rats (Weight= 280-300 g) for twelve consecutive days (20 min/day). Five minutes before exposure, the intruder rats received either saffron extract (1, 5, and 10 mg/kg) or saline (1 ml/kg). After the exposure, the animals’ weight, desire for the sucrose solution, and locomotor activity were recorded. In addition, at three stages, blood samples were collected from the retro-orbital sinus of animals to evaluate the plasma corticosterone levels. Data were analyzed in SPSS software using Kolmogorov-Smirnov test and repeated measures analysis of variance. Results: Animals in the stress group showed severe weight loss, decreased desire to drink sucrose solution, decreased mobility, and increased plasma corticosterone level (P<0.05). Administration of saffron aqueous extract with different doses improved these symptoms (P<0.01). Conclusion: The aqueous extract of saffron can reduce depression in the animal model of CSDS through reducing corticosterone secretion in response to stres

The effect of saffron and its constituent, crocin, on anterior pituitary-gonadal axis during pregnancy in the rat: A time-course study

Saffron is traditionally used in some developing countries for abortion. This study was aimed to investigate the effects of saffron aqueous extract and crocin, as one of its constituents, on the secretion of reproductive hormones in pregnant rats. The alteration of reproductive hormones was assayed in the early, middle, and late stages of pregnancy following the administration of different doses of saffron aqueous extract and crocin. Compared to the control group of each stage of pregnancy, the administration of an aqueous extract of saffron reduced estradiol levels in the early and late stages of pregnancy. A high dose of saffron extract in the middle and late stages of pregnancy and crocin in the late stages of pregnancy increased FSH serum levels. Saffron extract in the early stages and crocin in the late stages of pregnancy increase LH levels in a dose-dependent manner. The saffron extract reduces serum progesterone in all three stages of pregnancy. The current study indicated that the abortion effect of saffron is commonly exerted in the early and late stages of pregnancy. In addition, crocin has fewer effects on pregnancy than saffron and can only affect pregnant rats at high doses in the late stages of pregnancy.

Saffron (Crocus sativus L.) stigma reduces symptoms of morphine-induced dependence and spontaneous withdrawal in rats

ABSTRACT Background: Chronic morphine induces physical and psychological dependence signs. Saffron (Crocus sativus L.) stigma has been shown to have anxiolytic, antidepressant, and antinociceptive properties and to alleviate naloxone-precipitated withdrawal signs. Objectives: Therefore, this study was designed to examine the effects of saffron aqueous extract on the severity of physical-psychological dependence, voluntary morphine consumption, and the cerebrospinal fluid (CSF) serotonin levels following locomotor sensitization in morphine-dependent rats and in rats undergoing morphine withdrawal. Materials: Adult male rats were treated with morphine (10 mg/kg, sc twice daily) for 10 days. Rats received saffron extract (60 mg/kg, ip) daily, during the induction of morphine dependence and/or withdrawal. Then, rats were tested for spontaneous withdrawal signs, anxiety using the elevated plus-maze, depression using sucrose preference test, and voluntary morphine consumption using a two-bottle choice paradigm, and then challenged with morphine (1 mg/kg, ip) to evaluate of locomotor sensitization and CSF serotonin levels. Results: The results showed saffron extract during induction of morphine dependence decreased the severity of withdrawal signs (P = .05), while it had no effect on anxiety and depression-like behaviors. Saffron extract during morphine withdrawal exhibited an increase in the percentage (or ratio) of open/total arm entries (P = .017), higher levels of sucrose preference (P = .0001), a lower morphine preference ratio (P = .02) and also, a decrease in locomotor activity (P = .004) and an increase in the CSF serotonin levels (P = .041) in rats challenged to morphine. Conclusions: Saffron extract may exert a protective effect against morphine-induced behavioral sensitization in rats, probably through increasing serotonin levels.

Anticancer activity and antioxidant potential of Crocus Sativus .L( saffron ) aqueous extract against Ehrlich Ascites Carcinoma cells in Swiss albino mice.

Cancer is considered one of the most common causes of morbidity and mortality worldwide. Many chemopreventive agents have been associated with antiproliferative and apoptotic effects on cancer cells because of their high antioxidant activity. The current study was aimed to evaluate the anti-tumor, antioxidant and anti-inflammatory effects of Saffron aqueous extract and its active components against Ehrlich Ascites tumor (EAC). A total of 120 female mice were randomly divided into eight groups. The antitumor effect was assessed by evaluating tumor volume, tumor cell count , survival time and increase in life span of EAC bearing mice. The effect of Crocus Sativus .L ( saffron ) aqueous extract , Crocin and Safranal on different parameters (liver enzymes , kidney function , cardiac markers and antioxidant parameters). These results indicated that Saffron , Crocin and Safranal is a promising protective agents against EAC cells. . Crocus Sativus L ( saffron ) aqueous extract (100mg/kg), Crocin(10 mg/kg) and Safranal(1/10 LD50) (0.188 ml/kg) showed significantly decreased (p < 0.0001) in the volume of the EAC and in the count of EAC cells and increase the life span of EAC bearing mice. Also, showed significantly increased in antioxidant levels, decreased the lipid peroxidation( oxidative stress) as compared to positive control group . We found that The treatment of Crocus Sativus . L ( saffron ) aqueous extract , Crocin and Safranal significantly reduced the liver enzymes, cardiac markers and reduced elevated levels of Urea, Uric acid and Creatinine in positive control as compared with negative control and also increase the level of albumin as compared with positive control group . our data was confirmed by histopathological examination.

Saffron (Crocus sativus) aqueous extract reverses the hypothalamus-pituitary-adrenal axis activity in rat model of post-traumatic stress disorder

Crocus sativus L., Iridaceae, has been used worldwide in traditional medicinefor treatment ofsome neurological disorderssuch as depression. Post-traumatic stress disorder is a mental disorder developed in peoplewho experience stressful events. Since stress has been proposed tocause thehypothalamic-pituitary-adrenal axis malfunction in post-traumatic stress disorder patients, this study aimed at investigating the effect of saffron aqueous extract on hypothalamic-pituitary-adrenal axis activity in rats of post-traumatic stress disorder model. Here, Post-traumatic stress disorder animals received an acute electro foot shock; however, 5min before the stress session, these animals received an intra-cerebral-ventricular (10μg/rat) infusion of either saffron aqueous extract or saline. Twenty one days later, they were re-exposedto the stress box withoutinducing stress, andthen were examined for their freezing behavior. The impact of stress and saffron aqueous extract on serum corticosterone, corticotrophin releasing hormone gene expression in hypothalamus and glucocorticoid receptor gene expression in pituitary gland werethen evaluated on day 28. Intra-cerebral-ventricular injection of saffron aqueous extract resulted in an increase in serum corticosterone level and reduced symptoms of freezing behavior, and corticotrophin releasing hormone and glucocorticoid receptor gene expression in post-traumatic stress disorder groups.Saffron administration could improve the symptoms of stress-induced post-traumatic stress disorder, possiblythrough the adjustment ofhypothalamic-pituitary-adrenal axis function.

Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol toxicity in rats: A biochemical, histopathological and molecular study

Ethnopharmacological relevanceSaffron (Crocus sativus L.) is considered in the Iranian traditional medicine because of many therapeutic properties such as sedative agent, strengthen the stomach and liver, improving the uterus disorders and infectious wounds. The detoxification of alcohol was one of the most important of saffron effects in ancient medicine. Aim of the studyIn the current research, the protective effects of saffron aqueous extract (Aq. Ext.) versus oxidative stress, apoptosis, inflammation, histopathological and biochemical abnormalities induced by ethanol were evaluated. Materials & methodsThe male Wistar rats were divided into seven groups consisted of 6 rats in control (distilled water), ethanol (5 g/kg - 50% v/v), Aq. Ext. (40, 80 and 160 mg/kg) plus ethanol, Aq. Ext. 80 and 160 mg/kg. Animals were treated for four weeks and at the end of treatment period, histopathological damages, biochemical markers, apoptosis, levels of MDA and GSH, TNF-α and IL-6 were evaluated. ResultsEthanol induced nephrotoxicity and hepatotoxicity as evidenced by histopathological damages and biochemical abnormalities. The level of MDA was significantly enhanced while GSH content was remarkably reduced in ethanol-treated rats, but protective groups restored them. Also, the levels of TNF-α and IL-6 were regulated by Aq. Ext. Furthermore, the effects of ethanol on histopathological and biochemical parameters were improved by Aq. Ext. The ethanol increased the expression of Bax/Bcl2 ratio, caspase-3, -8, and -9. Real-time PCR and western blot analysis proved that Aq. Ext. treatment inhibited apoptosis induced by ethanol through decreasing the Bax/Bcl2 ratio (mRNA and protein) and caspases-3, -8, and -9 levels in the kidney and liver. ConclusionThe results of this research demonstrated that Aq. Ext. could exert protective effects against ethanol toxicity in rat kidney and liver via antioxidant, anti-apoptosis, and anti-inflammatory effects.

The Effect of Saffron Aqueous Extract and Crocin on PTSD Rat Models: The Focus on Learning and Spatial Memory

Background & Objective: Post traumatic stress disorder (PTSD) is an anxiety reaction, which occurs as a result of encountering a seriously traumatic event during one’s lifetime. The aim of this study was to evaluate the effect of saffron aqueous extract and crocin on spatial memory and learning with the Barnes maze in a PTSD model on male Wistar rats (Weighting 200–250 gr). Materials & Methods: Wistar rats (n=48) were randomly divided into two groups: PTSD and non-PTSD. The PTSD group first received intra-cerebero-ventricular (ICV) administration of 10 µg/rat aqueous saffron extract, crocin or saline and then an electric foot shock. After 21 days, both groups were returned to the electric shock box in order to remember stressors without receiving any shocks. Corticosterone levels were then measured in the samples. Concurrently, a digital camera was recording the animals’ behaviors. Upon this, spatial learning and memory was assessed for five consecutive days. Results: The saffron extract and crocin caused a significant increase (P<0.001) in corticosterone levels and a significant reduction (P<0.05) in freezing behavior, as well as a significant difference (P<0.001) in spatial learning of the two groups. Conclusion: Our results indicate the potential role of saffron aqueous extract and its active derivative (crocin) in improving behavioral symptoms and spatial learning in PTSD models.

The Effect of Saffron Aqueous Extract and Crocin on PTSD Rat Models: The Focus on Learning and Spatial Memory

Background & Objective: Post traumatic stress disorder (PTSD) is an anxiety reaction, which occurs as a result of encountering a seriously traumatic event during one’s lifetime. The aim of this study was to evaluate the effect of saffron aqueous extract and crocin on spatial memory and learning with the Barnes maze in a PTSD model on male Wistar rats (Weighting 200–250 gr). Materials & Methods: Wistar rats (n=48) were randomly divided into two groups: PTSD and non-PTSD. The PTSD group first received intra-cerebero-ventricular (ICV) administration of 10 µg/rat aqueous saffron extract, crocin or saline and then an electric foot shock. After 21 days, both groups were returned to the electric shock box in order to remember stressors without receiving any shocks. Corticosterone levels were then measured in the samples. Concurrently, a digital camera was recording the animals’ behaviors. Upon this, spatial learning and memory was assessed for five consecutive days. Results: The saffron extract and crocin caused a significant increase (P<0.001) in corticosterone levels and a significant reduction (P<0.05) in freezing behavior, as well as a significant difference (P<0.001) in spatial learning of the two groups. Conclusion: Our results indicate the potential role of saffron aqueous extract and its active derivative (crocin) in improving behavioral symptoms and spatial learning in PTSD models.

Effect of saffron aqueous extract on the level of blood glucose in experimental diabetes mice

To investigate the effects of saffron aqueous extract (SE) on blood glucose, lipid and pancreatic tissue in streptozocin-induced diabetes mice. Diabetes mellitus mice were established by intraperitoneal injection of streptozocin (60 mg/kg) for two consecutive days. The 30 well-established diabetes mice were randomly divided into three groups(n=10):diabetic mellitus (DM) group, SE treated (SE) group and positive control (metformin hydrochloride, MH) group. Another ten normal mice were selected as normal control (NC) group. The mice in SE and MH groups were intragastrically administered with SE 100 mg/kg or MH 100 mg/kg once a day for 6 weeks, mice in DM and NC were given normal saline. The amount of food-intake, water consumption and body weight were measured weekly, the changes of the indicators including fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), glycated serum protein (GSP), insulin (INS) and blood lipid were determined after 6 weeks of continuous administration. The pathologic changes in the pancreas tissues were detected by HE staining. Compared with the normal control group, the amount of food-intake, water consumption, area under the curve, FBG, GSP, and total cholesterol (TC) were significantly increased, while fasting weight, INS and high density lipoprotein cholesterol (HDL-c) were dramatically decreased in DM group. Compared with DM group, the water consumption, FBG, area under the curve and TC in SE group were starkly declined with a notable elevation of HDL-c and INS. In addition, the biopsy from DM mice showed the structure of pancreas islet was destroyed and reduced, and vascular proliferation with irregular shape. The damaged pancreas was obviously repaired by giving SE. The saffron aqueous extract had efficacy on blood glucose and blood lipids reduction, improvement on damaged pancreas in streptozocininduced diabetic mice, which suggested that saffron could be used for the treatment in diabetes.

Evaluation of the effects of saffron aqueous extract on oxidative stress in the lens of streptozotocin-induced diabetic rats

Background: Multiple-organ failure is the main cause of disability and death in diabetes mellitus. Imbalance in oxidative status is responsible for major diabetic complications and multiple-organ failure including blindness. Recently, plants with potential antioxidant properties have been used to manage hyperglycemia in diabetes. This study was undertaken to evaluate the beneficial effects of saffron aqueous extract (SAE) administration in streptozotocin (STZ)-induced diabetic rats by evaluation of oxidative stress parameters in the eye lens. Methods: Thirty-two adult rats were randomly divided into four groups: normal control (I), saffron control (II), diabetic control (III), and saffron treated (IV). Diabetes was induced in animals by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg body weight). Three days after STZ administration, diabetes was confirmed by measuring fasting blood glucose. At this time, groups II and IV were treated with SAE (200 mg/kg body weight) for a total of 5 doses, and then weekly from the 7th day after STZ injection. At the end of study, fasting blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as malondialdehyde (MDA) content were determined in the lens tissues. Results: In addition to the effects of SAE on blood glucose, SAE was effective on the enzymatic antioxidant defense system. The level of antioxidant enzymes (SOD, CAT, and GPx) decreased while there was an increase in the levels of MDA in the lens tissues of diabetic control rats, as compared to normal control rats. SAE could be modulating the changes in these parameters that are induced by diabetes. Conclusion: The results of the present study demonstrate that SAE is able to control blood glucose and thus may be useful in delaying the complicated effects of diabetes, such as clouding of the eyes’ lens due to the antioxidant effect of SAE.

Saffron Induced Relaxation in Isolated Rat Aorta via Endothelium Dependent and Independent Mechanisms.

Crocus sativus L. (saffron) is a widely used food additive for its color and taste. The hypotensive effects of saffron have been shown in previous studies. The aim of this study was to evaluate the mechanism of vasodilatory effects induced by saffron on isolated rat aorta. To study the vasodilatory effects of saffron aqueous extract (0.5, 1 and 2 mg/mL), isolated rat thoracic aorta rings were contracted by 10-6 M phenylephrine (PE) or KCl 80 mM. The vasodilatory effect of saffron was also evaluated both on intact and denuded endothelium aortic rings. To study the role of nitric oxide and prostacyclin in relaxation induced by saffron, aortic rings were incubated by L-NAME (10-6 M) and indomethacin (10-5 M) respectively for 20 min. Saffron induced relaxation in endothelium-intact aortic rings precontracted with PE in a concentration dependent manner. The obtained relaxation induced by the highest saffron concentration in endothelium-intact aortic rings precontracted with KCl was less than that observed in endothelium-intact aortic rings precontracted with PE. The relaxant activity of saffron was abolished by incubation of aortic rings with L-NAME but not in the presence of indomethacin. Also, the vasodilatory activity of saffron was partially abolished in endothelium denuded aortic rings. Saffron induced relaxation in isolated rat aortic rings might be due particularly to its effect on endothelium via nitric oxide synthase pathway and partly due to the effect on vascular smooth muscle cells via L type voltage dependent calcium channels.

Effect of saffron aqueous extract and its carotenoids (crocin and crocetin) on plasma proteome pattern, expression of SIRT1/LOX1 genes and miRNA-223, and serum homocysteine levels in atherosclerotic patients

Effect of saffron aqueous extract and its carotenoids (crocin and crocetin) on plasma proteome pattern, expression of SIRT1/LOX1 genes and miRNA-223, and serum homocysteine levels in atherosclerotic patients

The effect of Saffron aqueous extract on hepatocellular carcinoma rat model

The aim of this study was to investigate the tumor suppressive effects of saffron in an experimental hepatocellular carcinoma (HCC) model in rats. Thirty rats were included in this study and divided into:- Control group : Rats which receive distilled water only. HCC group : induced by diethylnitrosamine (DEN) and CCl4 only. Saffron group : Rats were administered orally saffron respectively 2 weeks prior to HCC initiation and continued for 6 weeks. The effect of saffron on ALT and AST activity and albumin level were studied also TGF-beta level and the TAC level were estimated and induction of apoptosis was determined by histopathological studies. Treatment with saffron was significantly decreased the activities of ALT and AST also increased the albumin level, decreased the TGF-beta level and increased the TAC level, it also reduced the elevation in the number and the incidence of hepatic dyschromatic nodules. Moreover, treatment with saffron extract brought significant restoration of the hematological parameters to values that were comparable to those of the negative control group, it also enhances the liver and kidney health, this study provides evidence that saffron exerts anti-oxidant, chemoperventive effect against liver cancer through induction of apoptosis as appeared in histopathological studies

Crocus sativus L. aqueous extract reduces atherogenesis, increases atherosclerotic plaque stability and improves glucose control in diabetic atherosclerotic animals

Background and aimsWe aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE−/−) mice. MethodsFifty male, ApoE−/− mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks). After blood sampling and euthanasia, aortic roots were excised and analyzed for gene expression and/or percentage of aortic stenosis, relative content of macrophages, smooth muscle cells (SMCs), connective tissue, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases-2,-3,-9 (MMP-2,-3,-9) and their inhibitor (TIMP-2) and IL-6. SFE doses were determined by a pilot serum pharmacokinetic study in C57BL/6J wild-type mice. ResultsSFE did not affect body weight and total cholesterol levels (p > 0.05), while high SFE dose significantly ameliorated glucose and triglycerides profiles compared to other groups (p < 0.05). SFE considerably decreased aortic stenosis in a dose-dependent manner (p < 0.05). Furthermore, increasing SFE doses proportionally reduced macrophages content and increased within plaques content of collagen, elastin, and SMCs, promoting more stable plaque phenotype compared to COG (p < 0.05). Those effects seemed to be associated with a considerable reduction (>30%) in IL-6, TNF-α, MCP-1, MMP-2,-3,-9 (p < 0.05) and MMP-2/TIMP-2 ratio. ConclusionsSFE exerted dose-dependent anti-atherosclerotic and plaque-stabilizing effects in Apo-E−/− mice, probably mediated by a favorable modification of inflammatory mechanisms, which requires further investigation.

Effects of Saffron Aqueous Extract and Its Main Constituent, Crocin, on Health-Related Quality of Life, Depression, and Sexual Desire in Coronary Artery Disease Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Background: Depression and sexual problems are common in patients with coronary artery disease (CAD) and can influence their quality of life. Objectives: The aim of this study was to compare the efficacy of saffron and its main constituent, crocin, in improving mental and sexual health and ultimately quality of life in CAD patients. Methods: This double-blind, placebo-controlled, randomized clinical trial was carried out during 8 weeks in 3 groups, including 1 placebo and 2 intervention groups. The study sample included 58 CAD patients within the age range of 40 - 65 years, referred to Shahid Madani cardiovascular hospital, Tabriz, Iran, from April 2015 to November 2016. The intervention groups received saffron aqueous extract (SAE; 30 mg; n, 20) or crocin (30 mg; n, 19). All the groups completed the demographic questionnaire, Beck depression inventory-II (BDI-II), Hulbert index of sexual desire (HISD), and MacNew health-related quality of life questionnaire. Results: The BDI-II score significantly decreased in the SAE (pre- and post test scores, 26.10 +/- 11.98 and 21.05 +/- 9.93, respectively) and crocin (pre- and post test scores, 27.89 +/- 8.46 and 22.68 +/- 8.01, respectively) groups (P < 0.001). After adjustments for age, sex, and diagnosis time, similar results were obtained. There was no significant difference between the crocin and SAE groups in terms of total BDI-II score at the end of the study (P = 0.999). SAE and crocin had no significant effects on HISD scores (P = 0.148 and 0.317, respectively). However, they could significantly improve the total quality of life and its subscales (P < 0.001). Conclusions: SAE and crocin could improve depression and health-related quality of life in patients with CAD, whereas they had no significant effects on sexual desire.

Reduction VEGF-A expression induced by saffron aqua extract with low frequency electromagnetic field in MCF-7 cell line

Background: Studies both invivo and invitro indicated anticancer and antitumor properties of saffron and its component against different human cancer cells which is wildly used as a drug to promote health and fight diseases from ancient time. Angiogenesis, formation of new blood vessels, is regulated by the balances of many stimulating and inhibiting factors. While physiological angiogenesis is under strike control, disruption of this control causes proliferation of a network of blood vessels penetrating into cancerous growth. One of the main factors which are involved in the process of angiogenesis in both physiologic and pathologic condition is VEGF-A. On the other hand, bio electromagnetic fields have been shown to be clinically beneficial in the mT amplitude range. The aim of this study was finding out if synergic effects of saffron aqueous extract and low-frequency electromagnetic field could decrease angiogenesis via reduction of VEGF-A gene expression.

Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice

Saffron stigma (Crocus sativus L.) is used for insomnia and anxiety in traditional medicine. In this study, the anxiolytic and hypnotic effects of saffron aqueous extract and its constituents, crocin and safranal, were studied in mice. Agents were administered intraperitoneally in mice before the experiments for the evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus maze test), locomotor activity (open field test) and motor coordination (Rotarod test). The aqueous extract reduced the locomotor activity dose dependently. At low doses, saffron showed a significant increase in the time on the open arms of the maze. When using the Rotarod method, the aqueous extract showed considerable effect on motor coordination of the mice. In the hypnotic test, only a dose of 0.56 g/kg of saffron increased the total sleep. Crocin showed no anxiolytic, hypnotic or myorelaxation effects. Safranal, in higher doses, 0.15 and 0.35 mL/kg, showed anxiolytic effects. Safranal increased the total sleep time dose dependently. This constituent at lower doses (0.05 and 0.15 mL/kg) decreased some locomotion activity parameters. Safranal demonstrated no effects on motor coordination. The results showed that saffron aqueous extract and safranal have anxiolytic and hypnotic effects.