• Journal of Pharmacopuncture
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• v.21 no.2
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• pp.61-69
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• 2018

Objective: In this study, the effects of saffron stigma against subacute diazinon (DZN) toxicity on enzymes levels, biochemical, hematological, histopathological and genotoxicity indices were studied in rats. Methods: Vitamin E (200 IU/kg) and the aqueous extract of saffron (50, 100 and 200 mg/kg) were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The hematological and biochemical parameters were evaluated at the end of 4 weeks. Results: Reticulocytes counts, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase, CPK-MB, gama glutamyl transferase (GGT), uric acid and micronucleus indices were increased significantly but total protein and RBC cholinesterase activity were decreased in the DZN-treated group. Saffron prevented the effect of DZN on GGT (50 mg/kg), LDH, CPK and CPK-MB (100 and 200 mg/kg) levels. An increased uric acid and reduced protein levels by DZN were prevented by vitamin E and some doses of saffron. A significant reduction was observed in platelets, RBC, hemoglobin and hematocrit indices in the DZN group. Saffron and vitamin E prevented this reduction. Vitamin E and saffron did not reduce the effect of DZN on RBC cholinesterase activity. The extract and vitamin E could not prevent DZN genotoxicity in the micronucleus assay. Other biochemical parameters and pathological evaluation did not show any abnormality in tissues of all groups. Conclusion: This study shows that vitamin E and saffron reduce DZN induced hematological and biochemical toxicity. However, they do not prevent the genotoxicity induced by DZN.

• Food Science and Biotechnology
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• v.18 no.4
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• pp.1038-1041
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• 2009

Aflatoxins are secondary metabolites produced by the aflatoxigenic fungi in suitable conditions. Saffron, Crocus sativus, is the most expensive spice in the world. Saffron is normally contaminated with soil and hand microflora during harvest and post-harvest operations. In this study, rapid assessment of aflatoxigenic fungi in saffron was accomplished using polymerase chain reaction. In total, 37 market samples were assayed in order to isolate aflatoxin-producing fungi. The 18.9% of the total samples were contaminated with aflatoxigenic fungi. Our results also show that most of the isolated fungi were saprophytes which are normally originated from soil during harvest and postharvest process.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6075-6080
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• 2014

Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.4
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• pp.163-169
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• 2018

Objective: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. Methods: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol ($E_2$), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. Results: Serum levels of LH, FSH, $E_2$, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. Conclusion: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.951-957
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• 2013

Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis.

• Journal of Pharmacopuncture
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• v.21 no.1
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• pp.35-40
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• 2018

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5605-5611
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• 2012

Background: In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery. Methods: In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock. Results: The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site. Conclusion: This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.

• Journal of Pharmacopuncture
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• v.21 no.4
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• pp.277-283
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• 2018

Objectives: Ethanol withdrawal following its chronic use is a serious outcome and challenging to treatment. The chronic use of ethanol induces a progressive neuroplasticity in different reigns of brain. In this study we evaluated the effects of aqueous extract of Crocus sativus L. (saffron) and its active compound, crocin, on the withdrawal behavior induced after repeated administration of ethanol, in two regimens of prophylactic (administration of drugs concomitant with the induction of dependence) and treatment (administration of drugs during the period of ethanol withdrawal) in mice which received ethanol. Methods: Ethanol dependence was induced by oral administration of 10% v/v ethanol (2 g/kg) for 7 days. The aqueous extracts of saffron (40, 80 and 160) and crocin (10, 20 and 40 mg/kg) were administered to mice in two regimens of prophylactic (along with ethanol) and treatment (during withdrawal period). Diazepam (1 mg/kg) was used as a positive control. Six hours after discontinuation of the ethanol, seizure was evaluated by the sub-convulsive dose of pentyleneltetrazole (PTZ) (30 mg/kg). The open field test and Rota rod test were used for evaluation of locomotor activity and motor incoordination, respectively. Results: Both extracts and crocin increased the number of crossed lined in the open field test. PTZ kindling seizure was inhibited in animals received extract (80 and 160 mg/kg) in both regimens. Motor incoordination was only improved following administration of crocin. Conclusion: The aqueous extract of saffron and crocin can be considered as safe agents and reliable alternative to diazepam in management of ethanol withdrawal syndrome.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.11
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• pp.1695-1704
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• 2019

Objective: This study investigated the effects of the administration of ethanolic saffron petal extract (SPE) and vitamin E (Vit E) on growth performance, blood metabolites and anti-oxidant status in Baluchi lambs. Methods: Thirty-two Baluchi male lambs ($35.22{\pm}5.75kg$) were randomly divided into 4 groups. The 1st (control), 2nd (injectable saffron petal extract [ISPE]), and 3rd (Vit E) groups were respectively injected subcutaneously with either physiological saline (5 mL), SPE (25 mg/kg body weight [BW]) or DL-${\alpha}$-tocopheryl acetate (225 IU) once a week. An oral dose of SPE (500 mg/kg BW) was also administered to the 4th group (oral saffron petal extract [OSPE]). Feed intake and BW were measured for 42 days and blood samples were taken on days 1, 14, 28, and 42. The lambs were slaughtered, and tissue samples were taken. Results: Growth performance and many blood metabolites were not affected (p>0.05) by the treatments. Cholesterol of plasma in the ISPE and Vit E groups was similar and less (p<0.01) than both the OSPE and control groups. Although there was no significant difference between the control and other groups for plasma triglyceride, the ISPE group showed lower (p<0.05) triglyceride than the OSPE and Vit E groups. The highest (p<0.01) plasma glutathione peroxidase (GPx) was detected in the OSPE group, while the ISPE and Vit E groups showed higher (p<0.01) superoxide dismutase (SOD) of plasma than the control. Malondialdehyde of plasma in the ISPE group was lower (p<0.05) than the OSPE. No differences (p>0.05) were observed among the groups for antioxidant status of both longissimus dorsi muscle and liver. However, the activity of GPx in the kidney and heart, as well as SOD activity in the kidney, were influenced ($p{\leq}0.01$) by the treatments. Conclusion: Adding ethanolic SPE improved antioxidant status and lowered lipids oxidation in lambs. The SPE and Vit E demonstrated similar effects on antioxidant status in lambs.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.329-335
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• 2016

Objectives: Safranal is a pharmacologically active component of saffron and is responsible for the unique aroma of saffron. The hypotensive effect of safranal has been shown in previous studies. This study evaluates the mechanism for the vasodilatory effects induced by safranal on isolated rat aortas. Methods: To study the vasodilatory effects of safranal (0.2, 0.4 and 0.8 mM), we contracted isolated rat thoracic aorta rings by using $10^{-6}-M$ phenylephrine (PE) or 80-mM KCl. Dimethyl sulfoxide (DMSO) was used as a control. The vasodilatory effect of safranal was also evaluated both on intact and denuded endothelium aortic rings. Furthermore, to study the role of nitric oxide and prostacyclin in the relaxation induced by safranal, we incubated the aortic rings by using L-NAME ($10^{-6}M$) or indomethacin ($10^{-5}M$), each for 20 minutes. Results: Safranal induced relaxation in endothelium-intact aortic rings precontracted by using PE or KCl in a concentration-dependent manner, with a maximum relaxation of more than 100%. The relaxant activity of safranal was not eliminated by incubating the aortic rings with L-NAME ($EC_{50}=0.29$ vs. $EC_{50}=0.43$) or with indomethacin ($EC_{50}=0.29$ vs. $EC_{50}=0.35$), where $EC_{50}$ is the half maximal effective concentration. Also, the vasodilatory activity of safranal was not modified by endothelial removal. Conclusion: This study indicated that relaxant activity of safranal is mediated predominantly through an endothelium-independent mechanism.