The CNS action of saffron is believed to be attributed to crocetin, a metabolite that is obtained from the crocin carotenoid and has been demonstrated to have a significant affinity for NMDA receptors. The activity of Caco-2 cells was measured by the MTT assay after 24 hours of incubation of cellular mitochondrial dehydrogenase with test compounds: hydroalcoholic saffron extract (SE, 0.5-1 mg/mL) and crocin-1 (250-1000 µM) did not show significant changes in cell viability with negative results. This was done to ensure that the viability of Caco-2 cells remained unchanged throughout the transport experiment. Cell viability is unaffected by crocetin at concentrations of 10 µM, but is considerably decreased at 40–160 µM [1].

Interactions
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. /Safranal and crocin/
Intragastric administration of 125-250.0 mg/kg body weight (bw) of a 50% ethanol extract of the stigmas had a tranquillizing effect in mice, and potentiated the sedative effects of barbiturates. /Ethanol extract of Stigma Croci/
Topical application of 100 mg/kg bw of a 95% ethanol extract of the stigmas inhibited two-stage initiation and promotion of skin carcinogenesis in mice, delaying the onset of papilloma formation and reducing the mean number of papillomas per mouse. Intragastric administration of 100.0 mg/kg bw of the same extract per day for 30 days reduced the incidence of soft tissue sarcomas induced by 20-methylcholanthrene by 10% in mice. Intragastric administration of 100.0 mg/kg bw of an ethanol extract of the stigmas to mice inhibited the growth of solid Dalton lymphoma ascites and sarcoma 180 tumors by 87% and 41%, respectively. Subcutaneous administration of 400.0 mg/kg bw of crocin weekly for 13 weeks, slowed the growth of colon adenocarcinoma and increased the lifespan of female but not male mice. /Ethanol extract of Stigma Croci/
Intraperitoneal administration of 50 mg/kg bw of a 95% ethanol extract of the stigmas to mice partially prevented the decreases in body weight, hemoglobin levels and leukocyte counts caused by cisplatin treatments. /Ethanol extract of Stigma croci/

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Non-Human Toxicity Values
LD50 Rats (male) 5.53 mL/kg /Safranal/
LD50 Rats (male) 1.5 mL/kg /Safranal/
LD50 Mice (female) i.p. 1.88 mL/kg /Safranal/
LD50 Mice(male) i.p. 1.48 mL/kg /Safranal/
For more Non-Human Toxicity Values (Complete) data for SAFFRON OIL (8 total), please visit the HSDB record page.

[1]. Intestinal formation of trans-Crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier. Phytomedicine. 2015 Jan 15;22(1):36-44.

[2]. Saffron: An Old Medicinal Plant and a Potential Novel Functional Food. Molecules. 2017 Dec 23;23(1). pii: E30.

Crocetin is a 20-carbon dicarboxylic acid which is a diterpenoid and natural carotenoid. Found in the crocus flower, it has been administered as an anti-fatigue dietary supplement. It has a role as a nutraceutical, a metabolite and an antioxidant. It is a carotenoic acid, a diterpenoid and a polyunsaturated dicarboxylic acid. It is a conjugate acid of a crocetin(2-).
Vitamin A-analog that increases diffusivity of oxygen in aqueous solutions, including plasma.
Crocetin has been reported in Gardenia jasminoides, Perilla frutescens, and other organisms with data available.

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Drug Indication
Investigated for use/treatment in cancer/tumors (unspecified), hemorrhage, hypoxia, respiratory failure, and strokes.

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Mechanism of Action
Trans sodium crocetinate is a novel drug, which has been shown to increase whole-body oxygen consumption during hemorrhagic shock. It works by increasing the diffusion rate of oxygen through plasma rather than on a specific symptom of hemorrhagic shock and has been suggested as a general treatment for hypoxemia. Thus it could also be beneficial for treating respiratory insufficiencies.

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Therapeutic Uses
EXPL THER The antitussive activity of Crocus sativus stigma and petal extracts and its components, safranal and crocin, was evaluated using the nebulized 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. /Extracts of Stigma Croci/
EXPL THER Crocus sativus L. (saffron) is used in folk medicine, for example as an antiedematogenic agent. /The authors/ aimed to evaluate the antinociceptive and anti-inflammatory activity of saffron extracts in mice. /They/ used aqueous and ethanolic maceration extracts of Crocus sativus L. stigma and petals. Antinociceptive activity was examined using the hot plate and writhing tests. The effect of extracts against acute inflammation was studied using xylene induced ear edema in mice. The activity of the extracts against chronic inflammation was assessed by formalin-induced edema in the rat paw. In the hot plate tests, intraperitoneal injection of both extracts showed no significant antinociceptive activity in mice. The extracts exhibited antinociceptive activity against acetic acid induced writhing. Naloxone partially blocked only the antinociceptive activity of the stigma aqueous extract. Only the stigma extracts showed weak to moderate effect against acute inflammation. In chronic inflammation, both aqueous and ethanolic stigma extracts, as well as ethanolic petal extract, exerted anti-inflammatory effects. /The authors/ conclude that aqueous and ethanolic extracts of saffron stigma and petal have an antinociceptive effect, as well as acute and/or chronic anti-inflammatory activity. /Stigma extracts/
EXPL THER Administration of a monthly intramuscular injection of crocetin (dose not specified) to rabbits fed an atherosclerosis-inducing diet reduced serum cholesterol concentrations by 50%, and reduced the severity of atherosclerosis by ~30%. /Crocetin/
EXPL THER The antioxidant effects of the stigmas were assessed in a clinical trial involving 30 subjects in three groups: 10 healthy volunteers, 10 patients with coronary artery disease and 10 healthy controls. The two test groups received 50 mg of Stigma Croci in 100.0 mL of milk twice daily for 6 weeks, the controls received milk only. Lipoprotein oxidation in blood samples decreased by 42.3% in healthy volunteers (P < 0.001) and 37.9% (P < 0.01) in patients with coronary artery disease compared with controls. /Stigma Croci/
For more Therapeutic Uses (Complete) data for SAFFRON OIL (7 total), please visit the HSDB record page.

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Drug Warnings
At doses of 5.0 g or more, Stigma Croci may cause serious adverse reactions. Overdose of Stigma Croci (12.0-20.0 g/day) may be fatal. /Stigma Croci/
Stigma Croci may induce uterine contractions and is therefore contraindicated during pregnancy. Owing to a lack of safety data, use of the stigmas in children and nursing mothers should be restricted to normal food use. Stigma Croci is contraindicated in bleeding disorders. /Stigma Croci/
Stigma Croci inhibits platelet aggregation and should therefore be used with caution in patients taking anticoagulant or antiplatelet drugs. /Stigma Croci/

C20H24O4

328.4022

328.167

27876-94-4

Crocetin disodium;591230-99-8;Crocetin meglumine

5281232

Yellow to orange solid powder

1.1±0.1 g/cm3

585.1±23.0 °C at 760 mmHg

285°

321.7±19.1 °C

0.0±3.5 mmHg at 25°C

1.559

4.72

2

4

8

24

608

0

C/C(=C\C=C\C=C(\C=C\C=C(\C(=O)O)/C)/C)/C=C/C=C(/C(=O)O)\C

PANKHBYNKQNAHN-MQQNZMFNSA-N

InChI=1S/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12-8+,15-9+,16-10+,17-13+,18-14+

(2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~1 mg/mL (~3.05 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)