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gamma-Tocotrienol

Cat No.:V12415 Purity: ≥98%
γ-Tocotrienol is an active form of vitamin E.
gamma-Tocotrienol
gamma-Tocotrienol Chemical Structure CAS No.: 14101-61-2
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
γ-Tocotrienol is an active form of vitamin E. γ-Tocotrienol can act on the NF-κB and P-gp signaling pathways to reverse multidrug resistance (MDR) in breast cancer/tumor cells. γ-Tocotrienol is also a new radioactive protective agent that can reduce radiation damage to bone marrow during radionuclide targeted therapy.
gamma-Tocotrienol (CAS#: 14101-61-2) is a member of the vitamin E family, which consists of four tocopherols and four tocotrienols. It has the molecular formula C28H44O2 and a molecular weight of 412.65 g/mol. gamma-Tocotrienol is a natural compound found in various foods, including palm oil, rice bran oil, and barley. It is a potent antioxidant with unique biological activities that distinguish it from the more common alpha-tocopherol.
Biological Activity I Assay Protocols (From Reference)
Targets
gamma-Tocotrienol acts as a potent antioxidant, scavenging free radicals and protecting cells from oxidative damage. Unlike tocopherols, tocotrienols have unsaturated side chains, which allow them to penetrate tissues with saturated fatty layers more efficiently, such as the brain and liver. gamma-Tocotrienol has been shown to inhibit the activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. It also has anti-inflammatory and neuroprotective properties.
ln Vitro
γ-Tocotrienol (25 μM; 24 h) efficiently suppresses P-gp protein and mdr1 mRNA expression levels. (25 μM and 50 μM; 24 h) also suppresses P-gp's efflux activity and mdr1 promoter activity. [2]. γ-Tocotrienol (at 25 μM and 50 μM; 24 hours) can decrease NF-κB transcriptional activity as well as the activation of the NF-κB signaling pathway [2]. γ-Tocotrienol (50 μM; 48 h) efficiently prevents the nuclear translocation of p65 caused by TNFα [2]. fluorescent imaging [2]
In vitro, gamma-tocotrienol exhibits potent antioxidant activity, protecting cells from oxidative stress induced by various agents. It also inhibits the proliferation of cancer cells and induces apoptosis in various cancer cell lines. It has been shown to reduce the production of inflammatory mediators and to protect neurons from glutamate-induced excitotoxicity.
ln Vivo
In myelosuppressive and fatal TBI in mice, the liposomal formulation of gamma-tocotrienol, GT3-Nano (20 mol% gamma-tocotrienol) (10 mg/kg, 6 mol%; intravenous injection; single dose, studied for 100 days), is efficacious in lowering sublethal [3]. Mice treated with the internal radiation therapy agent 153Sm-EDTMP can benefit from a fast recovery of hematopoietic components when administered GT3-Nano (50 mg/kg by intravenous injection) [3].
In vivo, gamma-tocotrienol has been studied for its potential to reduce cholesterol levels, protect against cardiovascular disease, and inhibit tumor growth. In animal models, it has shown neuroprotective effects in models of stroke and neurodegenerative diseases. It has also been studied for its potential to improve metabolic health and to protect against liver damage.
Enzyme Assay
The in vitro antioxidant assay for gamma-tocotrienol involves measuring its ability to scavenge free radicals. This is typically done using the DPPH (2,2-diphenyl-1-picrylhydrazyl) or ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging assay. The reduction in the absorbance of the radical is measured to determine the compound's antioxidant capacity.
Cell Assay
Immunofluorescence [2]
Cell Types: MCF-7/Adr Cell
Tested Concentrations: 50 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: The red fluorescence of p65 in the nucleus weakened, indicating that TNFα inhibits the nuclear translocation of p65.
In vitro cellular assays for gamma-tocotrienol are performed on various cell types, including cancer cells, neuronal cells, and immune cells. Cells are treated with gamma-tocotrienol, and parameters related to cell viability, apoptosis, inflammation, and oxidative stress are measured. For example, the induction of apoptosis is assessed using annexin V/PI staining and flow cytometry.
Animal Protocol
Animal/Disease Models: C57/BL6 black mouse (6-8 weeks old) total body irradiation [3]
Doses: 16, 24, 32, 50mg/kg
Route of Administration: intravenous (iv) (iv)injection; injection administration; mice were treated for 100 days Observations: Demonstrated dose-dependent radioprotection, achieving 90% survival against lethal 9 Gy total body irradiation (TBI) at a dose of 50 mg/kg. MPP2 and CMP are upregulated in bone marrow progenitor cells in GT3-Nano-treated mice.
In vivo animal experiments for gamma-tocotrienol are conducted in various models of disease. For stroke research, the middle cerebral artery occlusion (MCAO) model in mice or rats is used to assess its neuroprotective effects. For cancer research, xenograft models are used to evaluate its antitumor activity. For cardiovascular research, models of hypercholesterolemia are used to study its cholesterol-lowering effects.
ADME/Pharmacokinetics
Gamma-tocotrienol, like other vitamin E isoforms, is absorbed from the gastrointestinal tract and transported in lipoproteins. It is distributed to various tissues, with significant accumulation in the liver, brain, and adipose tissue. It is metabolized in the liver and excreted in urine and bile. Its half-life is shorter than that of tocopherols due to its rapid clearance.
Toxicity/Toxicokinetics
Gamma-tocotrienol is generally considered safe and well-tolerated. It has a low toxicity profile, and no significant adverse effects have been reported at doses commonly used in research. High doses may cause gastrointestinal disturbances. It is not known to be teratogenic or mutagenic. As a natural compound, it is widely consumed as part of a normal diet.
References

[1]. Nitric Oxide Synthase Activity in Blood Vessels of Spontaneously Hypertensive Rats: Antioxidant Protection by Gamma-Tocotrienol. J Physiol Pharmacol. 2003 Sep;54(3):319-27.

[2]. γ-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the γ-Tocotrienol-NF-κB-P-gp axis. J Steroid Biochem Mol Biol. 2021 May;209:105835.

[3]. γ-Tocotrienol-Loaded Liposomes for Radioprotection from Hematopoietic Side Effects Caused by Radiotherapeutic Drugs. J Nucl Med. 2021 Apr;62(4):584-590.

Additional Infomation
Gamma-tocotrienol is a tocotrienol with the structure chroman-6-ol, substituted with methyl groups at positions 2, 7, and 8, and a farnesyl chain attached at position 2. It is a member of the vitamin E family and possesses potent anti-cancer properties, capable of combating various cancers. It also exhibits antioxidant, antitumor, plant metabolism-enhancing, radiation-protective, apoptosis-inducing, and hepatoprotective effects. It is both a tocotrienol and vitamin E. Gamma-tocotrienol has been reported to exist in amaranth plants (such as hybrid amaranth and blood amaranth) and other organisms with relevant data.
Gamma-tocotrienol is a natural compound with significant research interest due to its unique biological activities. It is studied for its potential in preventing and treating various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Unlike alpha-tocopherol, which is the most common form of vitamin E, gamma-tocotrienol has been shown to have more potent antioxidant and anti-cancer properties in some studies. It is available as a dietary supplement.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C28H42O2
Molecular Weight
410.6319
Exact Mass
410.318
CAS #
14101-61-2
PubChem CID
5282349
Appearance
Colorless to light yellow liquid
Density
1.0±0.1 g/cm3
Boiling Point
530.8±49.0 °C at 760 mmHg
Flash Point
218.4±24.1 °C
Vapour Pressure
0.0±1.5 mmHg at 25°C
Index of Refraction
1.523
LogP
10.3
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
2
Rotatable Bond Count
9
Heavy Atom Count
30
Complexity
625
Defined Atom Stereocenter Count
1
SMILES
O1C2=C(C([H])([H])[H])C(C([H])([H])[H])=C(C([H])=C2C([H])([H])C([H])([H])[C@@]1(C([H])([H])[H])C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H])O[H]
InChi Key
OTXNTMVVOOBZCV-WAZJVIJMSA-N
InChi Code
InChI=1S/C28H42O2/c1-20(2)11-8-12-21(3)13-9-14-22(4)15-10-17-28(7)18-16-25-19-26(29)23(5)24(6)27(25)30-28/h11,13,15,19,29H,8-10,12,14,16-18H2,1-7H3/b21-13+,22-15+/t28-/m1/s1
Chemical Name
(2R)-2,7,8-trimethyl-2-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl]-3,4-dihydrochromen-6-ol
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~243.53 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: 2.5 mg/mL (6.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4353 mL 12.1764 mL 24.3528 mL
5 mM 0.4871 mL 2.4353 mL 4.8706 mL
10 mM 0.2435 mL 1.2176 mL 2.4353 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.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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