Transcrocetin (trans-Crocetin)
(Synonyms: 藏红花酸; trans-Crocetin) 目录号 : GC33341
A natural apocarotenoid with diverse biological activities
Cas No.:27876-94-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Cytotoxicity of test compounds is determined by MTT assay using Caco-2 cells in 96 well plates at a density of 20.000 cells per well in 200 µl FBS-free medium, grown for 96 h and followed by 24 h contact time with the test compounds (100 µL of serum-free media containing SE 0.5, 1, and 2 mg/mL; trans-crocin-1 250, 500, and 1000 µM; Transcrocetin 10, 40, 80, and 160 µM) and incubation at 37°C/5% CO2. The incubation solutions are aspirated, each well is washed twice with 150 µL of PBS and 50 µL of MTT solution are added (2.5 mg/mL in PBS). Supernatants are discarded and the formed formazan is dissolved in 50 µL of DMSO. The absorption of the resulting solution is determined at λ=492 nm against reference wavelength λ=690 nm[1]. |
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References: [1]. Lautenschläger M, et al. 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. |
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Transcrocetin is a natural apocarotenoid isolated from C. sativus and G. jasminoides that has antioxidant, antiproliferative, anti-inflammatory, cardioprotective, and antinociceptive properties.1,2,3,4,5,6 It scavenges 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (IC50 = 17.8 μg/ml) and inhibits growth of MKN28 stomach, MCF-7 breast, and Caco-2 colon cancer cell lines (IC50s = 53, 63, and 103 μM, respectively).2,3 Transcrocetin (20 μM) protects primary rat microglial cells from LPS-induced death and decreases LPS-induced production of intracellular reactive oxygen species (ROS), TNF-α, IL-1β, and NF-κB.4 Transcrocetin (100 mg/kg) increases the level of glutathione (GSH), catalase (CAT), creatine kinase (CK), and lactate dehydrogenase (LDH) in cardiac tissue in a rat model of myocardial infarction induced by isoproterenol .5 It also increases the pressure threshold and latency to withdrawal in response to mechanical and thermal stimuli, respectively, indicating a decrease in allodynia in a mouse model of spared nerve injury when administered intrathecally at a dose of 30 mg/kg.6
1.Pfister, S.L., Meyer, P., Steck, A., et al.Isolation and structure elucidation of carotenoid?glycosyl esters in gardenia fruits (Gardenia jasminoides Ellis) and saffron (Crocus sativus Linne)J. Agric. Food Chem.44(9)2612-2615(1996) 2.Kanakis, C.D., Tarantilis, P.A., Tajmir-Riahi, H.A., et al.Crocetin, dimethylcrocetin, and safranal bind human serum albumin: Stability and antioxidative propertiesJ. Agric. Food Chem.55(3)970-977(2007) 3.Oliveira, H., Cai, X., Zhang, Q., et al.Gastrointestinal absorption, antiproliferative and anti-inflammatory effect of the major carotenoids of Gardenia jasminoides Ellis on cancer cellsFood Funct.8(4)1672-1679(2017) 4.Nam, K.N., Park, Y.-M., Jung, H.-J., et al.Anti-inflammatory effects of crocin and crocetin in rat brain microglial cellsEur. J. Pharmacol.648(1-3)110-116(2010) 5.Zhang, W., Li, Y., and Ge, Z.Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat modelBiomed. Pharmacother.93376-382(2017) 6.Wang, X., Zhang, G., Qiao, Y., et al.Crocetin attenuates spared nerve injury-induced neuropathic pain in miceJ. Pharmacol. Sci.135(4)141-147(2017)
| Cas No. | 27876-94-4 | SDF | |
| 别名 | 藏红花酸; trans-Crocetin | ||
| Canonical SMILES | O=C(O)/C(C)=C/C=C/C(C)=C/C=C/C=C(C)/C=C/C=C(C)/C(O)=O | ||
| 分子式 | C20H24O4 | 分子量 | 328.4 |
| 溶解度 | DMSO : ≥ 33 mg/mL (100.49 mM) | 储存条件 | Store at -20°C,unstable in solution, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0451 mL | 15.2253 mL | 30.4507 mL |
| 5 mM | 0.609 mL | 3.0451 mL | 6.0901 mL |
| 10 mM | 0.3045 mL | 1.5225 mL | 3.0451 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
trans-Crocetin improves amyloid-β degradation in monocytes from Alzheimer's Disease patients
J Neurol Sci 2017 Jan 15;372:408-412.PMID:27865556DOI:10.1016/j.jns.2016.11.004.
Herbal medicines have been recently employed in research and clinical studies for the potential treatment of behavioral and psychological symptoms associated with Alzheimer's Disease (AD) and other types of dementia. The present study investigates the effect of trans-Crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability of AD patients' monocytes to degrade amyloid-β(1-42) (Aβ42). CD14+ monocytes from 22 sporadic AD patients with moderate cognitive impairment were isolated; then, the role of trans-Crocetin, purified from saffron extracts, was evaluated in terms of Aβ42 degradation rate through flow cytometry, as well as expression of cathepsin B by Western blotting. We observed that low micromolar doses of trans-Crocetin enhanced Aβ42 degradation in AD monocytes through the upregulation of the lysosomal protease cathepsin B. CA074Me, a potent and selective cathepsin B inhibitor, counteracted such trans-crocetin-induced effect. These data suggest that the carotenoid trans-Crocetin improves in vitro the clearance of Aβ42 through the involvement of cathepsin B, and this could be of value in developing a new anti-amyloid strategy in AD.
The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models
Front Neurosci 2019 Mar 26;13:249.PMID:30971876DOI:10.3389/fnins.2019.00249.
Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-Crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer's Disease (AD), utilizing two AD neuronal cell culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 cells. When tested on neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-Crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-Crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of cellular AβPP. When tested on the neuronally differentiated PC12-htau cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-Crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.
High-Purity Preparation of Enzyme Transformed trans-Crocetin Reclaimed from Gardenia Fruit Waste
Plants (Basel) 2022 Jan 21;11(3):281.PMID:35161261DOI:10.3390/plants11030281.
The recovery of physiologically bioactive ingredients from agricultural wastes as an abundant and low-cost source for the production of high value-added mutraceuticlas has been recognized and supported for the commercial interests and sustainable managements. In the extraction of geniposide for the development of natural food colorants from the dried fruits of Gardenia jasminoides Rubiaceae, the gardenia fruit waste (GFW) still remaining 0.86% (w/w) of crocins has always been discarded without any further treatments Until now, there was no simple and effective protocol for high-purity trans-crocein (TC) preparation without the coexistence of non-biologically active cis-crocein from GFW. We proposed an effective process to obtain the compound as follows. Crocins were extracted firstly by 50% of ethanol in the highest yield of 8.61 mg/g (w/w) from GFW. After the HPD-100 column fractionation in the collecting of crocins, the conversion ratio of 75% of crocins to crocetins can be obtained from the commercial available enzyme- Celluclast® 1.5 L. The crocins hydrolyzed products, were then separated through the HPD-100 resin adsorption and finally purified with the centrifugal partition chromatography (CPC) in single-step to obtain TC in a purity of 96.76 ± 0.17%. Conclusively, the effective enzyme transformation and purification co-operated with CPC technologies on crocins resulted in a high purity product of TC may be highly application in the commercial production.
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.PMID:25636868DOI:10.1016/j.phymed.2014.10.009.
Aims: Extracts of saffron (Crocus sativus L.) have traditionally been used against depressions. Recent preclinical and clinical investigations have rationalized this traditional use. trans-Crocetin, a saffron metabolite originating from the crocin apocarotenoids, has been shown to exert strong NMDA receptor affinity and is thought to be responsible for the CNS activity of saffron. Pharmacokinetic properties of the main constituents from saffron have only been described to a limited extent. Therefore the present in vitro study aimed to determine if crocin-1 and trans-Crocetin are able to pass the intestinal barrier and to penetrate the blood brain barrier (BBB). Additionally, the intestinal conversion of glycosylated crocins to the lipophilic crocetin had to be investigated. Experiments with Caco-2 cells and two different porcine BBB systems were conducted. Further on, potential intestinal metabolism of saffron extract was investigated by ex vivo experiments with murine intestine. Methodology: In vitro Caco-2 monolayer cell culture was used for investigation of intestinal permeation of crocin-1 and trans-Crocetin. In vitro models of porcine brain capillary endothelial cells (BCEC) and blood cerebrospinal fluid barrier (BCSFB) were used for monitoring permeation characteristics of trans-Crocetin through the blood brain barrier (BBB). Intestine tissue and feces homogenates from mice served for metabolism experiments. Results: Crocin-1, even at high concentrations (1000 µM) does not penetrate Caco-2 monolayers in relevant amounts. In contrast, trans-Crocetin permeates in a concentration-independent manner (10-114 µM) the intestinal barrier by transcellular passage with about 32% of the substrate being transported within 2 h and a permeation coefficient of Papp 25.7 × 10(-)(6) ± 6.23 × 10(-)(6) cm/s. trans-Crocetin serves as substrate for pGP efflux pump. trans-Crocetin permeates BBB with a slow but constant velocity over a 29 h period (BCEC system: Papp 1.48 × 10(-)(6) ± 0.12 × 10(-)(6) cm/s; BCSFB system Papp 3.85 × 10(-)(6) ± 0.21 × 10(-)(6) cm/s). Conversion of glycosylated crocins from saffron extract to trans-Crocetin occurs mainly by intestinal cells, rather than by microbiological fermentation in the colon. Conclusion: The here described in vitro studies have shown that crocins from saffron are probably not bioavailable in the systemic compartment after oral application. On the other side the investigations clearly have pointed out that crocins get hydrolyzed in the intestine to the deglycosylated trans-Crocetin, which subsequently is absorbed by passive transcellular diffusion to a high extend and within a short time interval over the intestinal barrier. Crocetin will penetrate in a quite slow process the blood brain barrier to reach the CNS. The intestinal deglycosylation of different crocins in the intestine is mainly due to enzymatic processes in the epithelial cells and only to a very minor extent due to deglycosylation by the fecal microbiome. On the other side the fecal bacteria degrade the apocarotenoid backbone to smaller alkyl units, which do not show any more the typical UV absorbance of crocins. As previous studies have shown strong NMDA receptor affinity and channel opening activity of trans-Crocetin the use of saffron for CNS disorders seems to be justified from the pharmacokinetic and pharmacodynamic background.
Liposomal encapsulation of trans-Crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation
J Control Release 2021 Aug 10;336:252-261.PMID:34175365DOI:10.1016/j.jconrel.2021.06.033.
Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-Crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.