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PubMed2005

Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats.

PURPOSE: The generation of reactive oxygen species and lipid peroxidation are associated with tissue injury following ischemic insult; therefore, the use of antioxidants appears rational in the improvement of kidney diseases therapy. The aim of the present study was to assess the effect of aqueous saffron extract (Crocus sativus L.) and its active constituent, crocin, on oxidative stress following renal ischemia-reperfusion injury (IRI) in rats. METHODS: The cellular redox status (thiobarbituric acid reactive species (TBARS) and total thiol levels) and antioxidant power (using ferric reducing/antioxidant power test) were assessed in control and ischemic groups. The left kidney was exposed to warm ischemia for 60 min followed by reperfusion for 90 min. The macerated aqueous extract of saffron (with doses of 5, 20 and 80 mg/kg, i.p.) and crocin (with doses of 50, 200 and 400 mg/kg, i.p.) were administrated prior to induction of ischemia. Normal saline (10 ml/kg, i.p.) was injected to control group and a sham group that did not have ischemia-reperfusion. RESULTS: Ischemia-reperfusion (IR) caused a significant increase in TBARS levels (p<0.001) and decrement in both antioxidant power (FRAP value) (p<0.05) and total thiol concentration (p<0.001) in kidney homogenate samples. In crocin pretreated groups, a reduction in TBARS levels (from 85.8 +/- 5.4 to 20.9 +/- 1.5 nmol/g tissue, p<0.001; 400 mg/kg) and elevation in antioxidant power (FRAP value) (from 3.05 +/- 0.16 to 4.15 +/- 0.16 micromol/g tissue, p<0.001; 400 mg/kg) and total thiol concentrations (from 0.38 +/- 0.03 to 0.62 +/- 0.03 mM, p<0.001; 200 mg/kg), as compared with control group, were observed. The aqueous extract also reduced lipid peroxidation products (from 85.8 +/- 5.4 to 15.9 +/- 2.6 nmol/g tissue, p<0.001; 80 mg/kg) and increased antioxidant power (from 2.98 +/- 0.11 to 5.97 +/- 0.56 micromol/g tissue, p<0.001; 80 mg/kg) in ischemia-reperfusion injured rat kidneys. CONCLUSION: This study therefore suggests that the aqueous saffron extract (Crocus sativus L.) and its active constituent, crocin, may be useful agents for the prevention of renal ischemia-reperfusion (IR)-induced oxidative injury in rats.

Animals↗

PubMed1991

Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice.

Topical application of Nigella sativa and Crocus sativus extracts (common food spices) inhibited two-stage initiation/promotion [dimethylbenz[a]anthracene (DMBA)/croton oil] skin carcinogenesis in mice. A dose of 100 mg/kg body wt of these extracts delayed the onset of papilloma formation and reduced the mean number of papillomas per mouse, respectively. The possibility that these extracts could inhibit the action of 20-methylcholanthrene (MCA)-induced soft tissue sarcomas was evaluated by studying the effect of these extracts on MCA-induced soft tissue sarcomas in albino mice. Intraperitoneal administration of Nigella sativa (100 mg/kg body wt) and oral administration of Crocus sativus (100 mg/kg body wt) 30 days after subcutaneous administration of MCA (745 nmol x 2 days) restricted tumor incidence to 33.3% and 10%, respectively, compared with 100% in MCA-treated controls.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Histopathological study of experimental acute poisoning of cattle by autumn crocus (Colchicum autumnale L.).

Crude or dehydrated bulbs of autumn crocus (Colchicum autumnale L.) were fed to eleven calves. All the calves developed severe diarrhea and died or euthanized within 63 hr. At necropsy, the gastro-intestinal mucosa was edematous and hemorrhagic. Histologically, necrosis and degeneration with karyopyknosis and karyorrhexis were shown in the basal cell layer of the tongue, esophagus, forestomach, renal pelvis, urinary bladder, neck cell layer of the abomasal gastric glands, and intestinal cryps. These findings were also seen in Kupffer cells, renal tubular epithelial cells, and lymphocytes in the lymphoid and hemopoietic systems. The lesion of the present acute crocus poisoning of cattle closely resembled those reported in humans with colchicine intoxication. Refined acetone extract of organs of poisoned cattle proved to contain colchicine and demecolcine by high performance liquid chromatography.

Animals↗

PubMedDate not supplied

Inhibition of growth and induction of differentiation of promyelocytic leukemia (HL-60) by carotenoids from Crocus sativus L.

The effects of carotenoids of Crocus sativus L. (saffron) on cell proliferation and differentiation of HL-60 cells have been studied and compared with those of all-trans retinoic acid. Our results demonstrated that the doses inducing 50% inhibition of cell growth were 0.12 microM for all-trans retinoic acid (ATRA) and for carotenoids of saffron 0.8 microM for dimethylcrocetin (DMCRT), 2 microM for crocetin CRT and 2 microM for crocins (CRCs). At 5 microM, all these compounds induced differentiation of HL-60 cells, at 85% for ATRA, 70% for DMCRT, 50% for CRT and 48% for CRCs. In these experiments, leukemic cells were cultured for 5 days in the absence or in the presence of up to 5 microM ATRA or seminatural and natural carotenoids. Since retinoids have a potential application as chemopreventive agents in humans, their toxicity as an important limiting factor for their use in treatment should be extensively explored. The seminatural (DMCRT and CRT) and natural carotenoids (CRCs) of Crocus sativus L. are not provitamin A precursors and could therefore be less toxic than retinoids, even at high doses.

Carotenoids↗

PubMed2003

Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice.

The modifying effects of the aqueous extract of saffron (dried stigmas of Crocus sativus Linn.) on cisplatin (CIS), cyclophosphamide (CPH), mitomycin-C (MMC) and urethane (URE) induced alterations in lipid peroxidation and antioxidant status were investigated in Swiss albino mice. Three doses of saffron (20, 40 and 80 mg/kg body weight) were orally administered to mice for 5 consecutive days prior to administration of genotoxins. A significant reduction in the extent of lipid peroxidation with a concomitant increase in the liver enzymatic (SOD, CAT, GST, GPx) and non-enzymatic antioxidants (reduced glutathione) were observed in saffron pretreated animals compared with the genotoxins alone treated animals. However, the modulatory effects were not always dose dependent. Our data suggest that saffron may exert its chemopreventive effects by modulation of lipid peroxidation, antioxidants and detoxification systems.

Animals↗

PubMed2006

Crocus sativus L. extracts antagonize memory impairments in different behavioural tasks in the rat.

The effects of extracts of Crocus sativus L. (CSE), on memory were investigated in the rat by using the object recognition and the step-through passive avoidance task. In the first study, post-training administration of CSE (30 and 60 g/kg) successfully counteracted extinction of recognition memory in the normal rat, suggesting that CSE modulates storage and/or retrieval of information. In a subsequent study, pre-training treatment with CSE (30 and 60 mg/kg) significantly antagonized the scopolamine (0.75 mg/kg)-induced performance deficits in the step-through passive avoidance test. These results support and extend prior findings about the implication of CSE in learning and memory mechanisms.

Animals↗

PubMed2005

Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice.

The anticonvulsant activities of Crocus sativus stigma constituents, safranal and crocin, were evaluated in mice using pentylenetetrazole (PTZ)-induced convulsions in mice. Safranal (0.15 and 0.35 ml/kg, i.p.) reduced the seizure duration, delayed the onset of tonic convulsions and protected mice from death. Crocin (200 mg/kg, i.p.) did not show anticonvulsant activity.

Animals↗

PubMed2006

Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs.

The antitussive activity of Crocus sativus stigma and petal extracts and its components, safranal and crocin, was evaluated using the nebolized solution of citric acid 20% in guinea pigs. The extract and agents were injected intraperitoneally. The ethanolic extract of C. sativus (100-800 mg/kg) and safranal (0.25-0.75 ml/kg) reduced the number of cough. The ethanolic and aqueous extracts of petal and crocin did not show antitussive activity.

Animals↗

PubMed2006

Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial.

Depression is a major worldwide health problem. Indeed, by 2020, depressive disorders are estimated to represent the second largest disease burden worldwide. Although a variety of pharmaceutical agents are available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. Our objective was to assess the efficacy of petal of Crocus sativus in the treatment of mild-to-moderate depression in a 6-week double-blind, placebo-controlled and randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM IV participated in the trial. In this double-blind, placebo-controlled and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, petal of C. sativus produced a significantly better outcome on Hamilton Depression Rating Scale than placebo (d.f.=1, F=16.87, p<0.001). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of petal of C. sativus in the treatment of mild-to-moderate depression. A large-scale trial is justified.

Adult↗

PubMed2006

Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial.

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.

Adult↗

PubMed2003

Effects of Crocus sativus petals' extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum.

We have investigated the effects of Crocus sativus petals' extract on blood pressure in anaesthetised rats and also on responses of the isolated rat vas deferens and guinea-pig ileum induced by electrical field stimulation (EFS). Aqueous and ethanol extracts of C. sativus petals reduced the blood pressure in a dose-dependent manner. For example administration of 50 mg/100 g of aqueous extract changed the blood pressure from 133.5+/-3.9 to 117+/-2.1 (mmHg). EFS of the isolated rat vas deferens and guinea-pig ileum evoked contractions were decreased by aqueous and ethanol extracts of C. sativus petals. The aqueous extract (560 mg/ml) significantly reduced the contractile responses of vas deferens to epinephrine (1 microM) without any change in contraction induced by KCl (300 mM). The present results may suggest that the relaxatory action of C. sativus petals' extract on contraction induced by EFS in the rat isolated vas deferens is a postsynaptic effect.

Anesthesia↗

PubMedDate not supplied

Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.).

Saffron is harvested from the dried, dark red stigmas of Crocus sativus L. flowers. It is used as a spice for flavoring and coloring food and as a perfume. It is often used for treating several diseases. We assessed the antimutagenic, comutagenic and cytotoxic effects of saffron and its main ingredients using the Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro colony formation assay and four different cultured human normal (CCD-18Lu) and malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the Ames/Salmonella test system, saffron showed non-mutagenic, as well as non-antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose-dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component responsible for this unusual comutagenic effect was safranal. In the in vitro colony formation test system, saffron displayed a dose-dependent inhibitory effect only against human malignant cells. All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components might be used as potential cancer chemopreventive agents.

Anthracenes↗

PubMed2006

Crocetin esters, picrocrocin and its related compounds present in Crocus sativus stigmas and Gardenia jasminoides fruits. Tentative identification of seven new compounds by LC-ESI-MS.

Crocetin esters present in saffron (Crocus sativus L.) stigmas and in Gardenia jasminoides Ellis fruit are the compounds responsible for their color. Of the fifteen crocetin esters identified in this study, five new compounds were tentatively identified: trans and cis isomers of crocetin (beta-D-triglucoside)-(beta-D-gentibiosyl) ester, trans and cis isomers of crocetin (beta-D-neapolitanose)-(beta-D-glucosyl) ester, and cis crocetin (beta-D-neapolitanose)-(beta-D-gentibiosyl) ester. The most relevant differences between both species were a low content of the trans crocetin (beta-D-glucosyl)-(beta-D-gentibiosyl) ester, the absence of trans crocetin di-(beta-D-glucosyl) ester in gardenia, and its higher content of trans crocetin (beta-D-gentibiosyl) ester and cis crocetin di-(beta-D-gentibiosyl) ester. With the same chromatographic method it was possible to identify, in a single run, ten glycosidic compounds in saffron extracts with a UV/vis pattern similar to that of picrocrocin; among them, 5-hydroxy-7,7-dimethyl-4,5,6,7-tetrahydro-3H-isobenzofuranone 5-O-beta-D-gentibioside and 4-hydroxymethyl-3,5,5-trimethyl-cyclohexen-2-one 4-O-beta-D-gentibioside were tentatively identified for the first time in saffron. Of these ten glycosides, only the O-beta-D-gentibiosyl ester of 2-methyl-6-oxo-2,4-hepta-2,4-dienoic acid was found in gardenia samples, but it was possible to identify the iridoid glycoside, geniposide.

Carotenoids↗

PubMed2006

Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents.

Crocus sativus stigmas are one of the widely known spices (saffron) and consist of unusually polar carotenoids. Alzheimer's disease is characterized pathologically by deposition of amyloid beta-peptide (Abeta) fibrils. Oxidation is thought to promote Abeta fibril formation and deposition. To identify agents inhibiting the pathogenesis of Alzheimer's disease, we examined in vitro the antioxidant properties of extract of C. sativus stigmas and its effect on Abeta(1-40) fibrillogenesis. The antioxidant properties were determined by measuring the ferric-reducing antioxidant power and Trolox-equivalent antioxidant capacity, while its effects on Abeta-aggregation and fibrillogenesis were studied by thioflavine T-based fluorescence assay and by DNA binding shift assay. The water:methanol (50:50, v/v) extract of C. sativus stigmas possesses good antioxidant properties, higher than those of tomatoes and carrots, and inhibited Abeta fibrillogenesis in a concentration and time-dependent manner. The main carotenoid constituent, trans-crocin-4, the digentibiosyl ester of crocetin, inhibited Abeta fibrillogenesis at lower concentrations than dimethylcrocetin, revealing that the action of the carotenoid is enhanced by the presence of the sugars. Our findings suggest the possible use of C. sativus stigma constituents for inhibition of aggregation and deposition of Abeta in the human brain.

Amyloid beta-Peptides↗

PubMed2002

Constituents of the stigmas of Crocus sativus and their tyrosinase inhibitory activity.

Four new compounds, crocusatins F (1), G (2), H (3), and I (4a), together with 21 known compounds, were isolated from an aqueous extract of the stigmas of Crocus sativus (saffron). The structures of 1-4 were established by spectral methods. The tyrosinase inhibitory activities of all 25 compounds isolated were evaluated in vitro using mushroom tyrosinase. Among them, crocusatin H (3), crocin-1 (5), and crocin-3 (6) showed significant tyrosinase inhibitory activity.

Crocus↗

PubMed2004

Antityrosinase principles and constituents of the petals of Crocus sativus.

Three new monoterpenoids, crocusatin-J (1), -K (2), and -L (3), and a new naturally occurring acid, (3S),4-dihydroxybutyric acid (4), together with 31 known compounds were isolated and identified from the methanol extract of the petals of saffron (Crocus sativus). Their structures were established by spectroscopic methods. Among them, crocusatin-K (2), crocusatin-L (3), and 4-hydroxy-3,5,5-trimethylcyclohex-2-enone (8) showed significant antityrosinase activity, and protocatechuic acid (18), kaempferol (24), and kaempferol 7-O-beta-d-glucopyranoside (27) were more effective in scavenging alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals than alpha-tocopherol. In addition, the mechanism of tyrosinase inhibition by crocusatin-K (2) is also discussed.

China↗

PubMed2002

Thermal stability of catalases active in dormant saffron (Crocus sativus L.) corms.

Catalase activity was detected in crude extract prepared from dormant saffron (Crocus sativus L.) corms. The activity was independent of pH in the range 6.0-11.0. Thermostability studies suggested the presence of three isoenzymes with transition temperatures of 30 degrees C, 45 degrees C and 60 degrees C, respectively, as given by Arrhenius plots. When stained for catalase activity gel electropherograms of extract revealed 3 distinct bands with apparent molecular weight of 323,000, 295,000 and 268,000, respectively. Thus it appeared that at least three isoenzymes of catalase were present in dormant saffron corms.

Catalase↗

PubMed2004

Promotion of the growth of Crocus sativus cells and the production of crocin by rare earth elements.

La3+ and Ce3+, either singly or a mixture, promoted crocin production of Crocus sativus callus but Nd3+ had little effect and all metal ions were toxic above 100 microM. La3+ (60 microM) promoted growth of callus significantly but increased crocin only slightly. Ce3+ (40 microM) significantly promoted crocin production but had little effect on cell growth. La3+ (60 microM) and Ce3+ (20 microM) together gave the highest dry weight biomass (20.4 g l(-1)), crocin content (4.4 mg g(-1)) and crocin production (90 mg l(-1)) which were, respectively, 1.7-fold, 4.2-fold and 7.1-fold of those without additions. Nd3+ (40 microM) only slightly promoted cell growth and crocin production.

Carotenoids↗