| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
The compound is thought to exert its central nervous system activity through high affinity to the phencyclidine binding site of the NMDA receptor, leading to antagonistic effects and inhibition of glutamatergic transmission. [1]
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| ln Vitro |
The saffron metabolite disodium crocetin, also known as trans-crocetin, is assumed to be the cause of the CNS activity of saffron. It is generated from the crocin carotenoid and has been demonstrated to have a significant affinity for NMDA receptors. After incubating with test compounds for 24 hours, the cellular mitochondrial dehydrogenase activity of Caco-2 cells was measured by the MTT assay to ensure constant viability. The results revealed no significant negative changes in cell viability for hydroalcoholic saffron extract, saffron extract (SE, 0.5-1 mg/mL), and crocin-1 (250-1000 µM). At 10 µM, disodium crocetin has little effect on cell viability; nevertheless, at doses between 40 and 160 µM, cell viability is dramatically reduced [1].
trans-crocetin permeates Caco-2 cell monolayers in a concentration-independent manner within the tested range of 10–114 μM, with approximately 32% of the substrate being transported within 2 hours from the apical to the basolateral side. The mean apparent permeability coefficient (Papp) was calculated as 25.7 × 10⁻⁶ ± 6.23 × 10⁻⁶ cm/s. [1] Mechanistic studies revealed that trans-crocetin is a substrate for the p-glycoprotein (p-gp) efflux pump, as its permeability increased in the presence of the inhibitor verapamil (50 μM). It is not transported via the paracellular route, as pre-incubation with EDTA did not enhance its transport. It is also not a substrate for cholesterol transporters (SR-BI, NPC1L1, ABCA1), as its permeation was unaffected by the inhibitor ezetimibe (15 μM). [1] In two different in vitro porcine blood-brain barrier models, trans-crocetin permeated slowly but constantly over a 29-hour period. In the brain capillary endothelial cells model, the apparent permeability coefficient was 1.48 × 10⁻⁶ ± 0.12 × 10⁻⁶ cm/s. In the blood cerebrospinal fluid barrier model, the apparent permeability coefficient was 3.85 × 10⁻⁶ ± 0.21 × 10⁻⁶ cm/s. The presence of verapamil did not alter its permeation in the BCEC model. [1] |
| Enzyme Assay |
No direct enzyme assays (e.g., for Ki, IC50) were performed for trans-crocetin in this study. However, the study investigated the enzymatic conversion of its precursor, crocins, to trans-crocetin. A protein-enriched supernatant was obtained by homogenizing freshly isolated mouse small intestine, diluting the homogenate, and centrifuging it at 500 × g for 10 minutes at 4°C. This supernatant was then incubated with a saffron extract (containing various crocins) in a buffer supplemented with D-glucose, at 37°C with gentle shaking at 200 rpm for 5 hours. Samples were taken hourly and analyzed by UPLC. The results showed that the deglycosylation of crocins to trans-crocetin is mediated by enzymatic activity of intestinal cells, likely esterases or β-glycosidases. [1]
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| Cell Assay |
The permeability of trans-crocetin was assessed using Caco-2 cell monolayers. Cells were seeded at a density of 2 × 10⁵ cells/mL on polycarbonate membrane Transwell inserts and cultured for 21-23 days. The integrity of the monolayers was monitored by measuring transepithelial electrical resistance, with only inserts having values >150 Ω·cm² used for experiments. Transport studies were performed at 37°C, where test compounds were added to the donor compartment. Samples were taken from the receiver compartment every 30 minutes over a 2-hour period. The apparent permeability coefficient was calculated from the cumulative amount of trans-crocetin transported. [1]
The cytotoxicity of trans-crocetin on Caco-2 cells was evaluated using an MTT assay. Cells were seeded in 96-well plates at a density of 20,000 cells per well and grown for 96 hours. They were then exposed to various concentrations of trans-crocetin for 24 hours. Following incubation, an MTT solution was added, and the resulting formazan crystals were dissolved in DMSO. The absorbance was measured at 492 nm with a reference at 690 nm. Concentrations of 10 μM showed no significant effect on viability, while concentrations between 40–160 μM significantly reduced cellular viability. [1] Two in vitro blood-brain barrier models were used: primary porcine brain capillary endothelial cells and primary porcine blood-cerebrospinal fluid barrier (choroid plexus epithelial cells). These cells were cultured on Transwell inserts. Barrier integrity was validated by measuring TEER (600-900 Ω·cm²) using impedance spectroscopy. Transport experiments were extended to 29 hours, with samples drawn from the acceptor compartments at 4, 7, 23, and 29 hours to quantify the permeation of trans-crocetin. [1] |
| Animal Protocol |
However, tissue and fecal homogenates from mice were used for ex vivo metabolism studies. Small intestine, appendix, and colon were obtained from C57Bl/6N mice (3 months to 1 year old). The small intestine was homogenized on ice to obtain a tissue homogenate, which was then centrifuged to prepare a protein-enriched supernatant for incubation experiments. Fecal contents from the appendix and colon were also homogenized to prepare a feces-enriched supernatant for similar incubations. [1]
However, tissue and fecal homogenates from mice were used for ex vivo metabolism studies. Small intestine, appendix, and colon were obtained from C57Bl/6N mice (3 months to 1 year old). The small intestine was homogenized on ice to obtain a tissue homogenate, which was then centrifuged to prepare a protein-enriched supernatant for incubation experiments. Fecal contents from the appendix and colon were also homogenized to prepare a feces-enriched supernatant for similar incubations. [1] |
| ADME/Pharmacokinetics |
trans-crocetin is the deglycosylated metabolite formed from crocins (the main glycosylated constituents of saffron) in the intestine. This conversion is primarily mediated by enzymes in the intestinal epithelial cells, rather than by the fecal microbiome. [1]
trans-crocetin is highly absorbed across the intestinal barrier via passive transcellular diffusion, with about 32% transported within 2 hours in an in vitro Caco-2 model. Its absorption is concentration-independent in the range of 10–114 μM. It serves as a substrate for the p-gp efflux pump in the intestine. [1] Following intestinal absorption, trans-crocetin can penetrate the blood-brain barrier in vitro, albeit at a slow rate, with permeation coefficients of 1.48 × 10⁻⁶ cm/s in a BCEC model and 3.85 × 10⁻⁶ cm/s in a BCSFB model over a 29-hour period. [1] Incubation with fecal homogenate leads to a significant reduction (about 80%) of total crocins, but only a minimal amount (<1%) of trans-crocetin is formed, indicating that fecal bacteria primarily degrade the apocarotenoid backbone to smaller, non-UV-absorbing alkyl units. [1] |
| Toxicity/Toxicokinetics |
In an MTT assay using Caco-2 cells, trans-crocetin at a concentration of 10 μM did not significantly alter cell viability. However, exposure to higher concentrations in the range of 40–160 μM for 24 hours resulted in a significant reduction in cellular viability. [1]
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| References | |
| Additional Infomation |
Sodium trans-crocin is the sodium salt of the trans isomer of carotenoid crocin and possesses potential anti-hypoxia and radiosensitizing activities. Sodium trans-crocin (TSC) can increase the diffusion rate of oxygen in aqueous solutions, such as from plasma to body tissues. Studies have shown that this substance can increase oxygen supply in hypoxic and ischemic conditions that may occur in hemorrhage, vascular and nervous system diseases, and tumor microenvironments.
trans-crocetin is the deglycosylated metabolite of crocins, the main apocarotenoids in saffron (Crocus sativus L.). It is considered the active principle responsible for the central nervous system activity of saffron. Its mechanism of action is attributed to its high affinity for the phencyclidine binding site of the NMDA receptor, which leads to antagonistic effects and the inhibition of glutamatergic synaptic transmission. [1] The study's findings support the traditional use of saffron for central nervous system disorders from a pharmacokinetic and pharmacodynamic perspective. The data demonstrate that after oral ingestion, the inactive glycosylated crocins are metabolized in the intestine to the active, absorbable trans-crocetin, which can subsequently cross the blood-brain barrier to reach its site of action. [1] |
| Molecular Formula |
C20H22NA2O4
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|---|---|
| Molecular Weight |
372.3715
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| Exact Mass |
372.131
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| CAS # |
591230-99-8
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| Related CAS # |
Crocetin meglumine;Crocetin;27876-94-4
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| PubChem CID |
10287099
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| Appearance |
Orange to reddish brown solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C\C=C\C=C(\C=C\C=C(\C(=O)[O-])/C)/C)/C=C/C=C(/C(=O)[O-])\C.[Na+].[Na+]
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| InChi Key |
RMDMBHQVNHQDDD-VFWKRBOSSA-L
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| InChi Code |
InChI=1S/C20H24O4.2Na/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);;/q;2*+1/p-2/b6-5+,11-7+,12-8+,15-9+,16-10+,17-13+,18-14+;;
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| Chemical Name |
disodium;(2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate
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| Synonyms |
Trans-crocetin sodium Transcrocetin sodiumTrans-crocetinate sodium Sodium crocetinate Trans-crocetinate sodium NSC 407300 CrocetinTSC
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~16.67 mg/mL (~44.77 mM)
DMSO : ~1 mg/mL (~2.69 mM) |
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6855 mL | 13.4275 mL | 26.8550 mL | |
| 5 mM | 0.5371 mL | 2.6855 mL | 5.3710 mL | |
| 10 mM | 0.2686 mL | 1.3428 mL | 2.6855 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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