| Size | Price | Stock | Qty |
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| 1g |
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| 10g |
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| Other Sizes |
| Targets |
DNA methyltransferase 1 (DNMT1) (IC50 = 3.2 μmol/l)
DNA methyltransferase 3a (DNMT3a) (IC50 = 22.3 μmol/l) DNA methyltransferase 3b (DNMT3b) (maximum inhibition 57%) Oestrogen-related receptor γ (ERRγ) (partial antagonist; approximately 40% reduction of innate activity at tested concentrations) [1] |
|---|---|
| ln Vitro |
γ-Oryzanol suppresses DNMT1 (IC50=3.2 μM), DNMT 3a (IC50=22.3 μM), and DNMT 3b (highest inhibition rate: 57%). Conversely, ferulic acid, γ-oryzanol's metabolite, has substantially less inhibitory activity than γ-oryzanol. Moreover, ERRγ primarily functions as a positive regulator of DNMT1 synthesis, which lowers the activity of DNMT1, and γ-Oryzanol can function as a partial antagonist of ERRγ [1].
γ-Oryzanol significantly inhibited the activities of DNMT1 (IC50 = 3.2 μmol/l), DNMT3a (IC50 = 22.3 μmol/l) and DNMT3b (maximum inhibition 57%) in enzymatic assays. Ferulic acid, a metabolite of γ-oryzanol, showed much lower inhibitory activity than γ-oryzanol. [1] In non-human mammalian reporter cells constitutively expressing active ERRγ, γ-oryzanol partially decreased ERRγ activity (approximately 40% reduction of the innate value). [1] Michaelis-Menten kinetics and Eadie-Hofstee analysis demonstrated that γ-oryzanol inhibited DNMT1 in a competitive manner (increased Km without affecting Vmax), while it inhibited DNMT3a and DNMT3b in a non-competitive manner (decreased both Vmax and Km). [1] |
| ln Vivo |
By lowering hypothalamic endoplasmic reticulum (ER) stress, brown rice's special bioactive ingredient, γ-oryzanol—a blend of ferulate and several phytosterols—attenuates demand for dietary fat. γ-oryzanol has the ability to ameliorate HFD-induced DNA hypermethylation in the mouse striatum's D2R promoter region. A striatal-specific regulation of DNMT levels may be attributed to γ-oryzanol. ERRγ activity is partially reduced by γ-oryzanol (around 40% reduction in inherent value). Gamma-oryzanol given orally by gavage to male mice considerably reduced their liking for HFD (93% of the value in mice treated with a vehicle), which in turn led to a significantly reduced rate of weight gain [1].
Oral administration of γ-oryzanol to male mice (via gavage or as 0.4% HFD supplement) significantly attenuated the preference for an HFD (93% of the values for vehicle-treated mice), resulting in an apparent attenuation of body weight gain. [1] In HFD-fed mice, γ-oryzanol significantly decreased striatal DNA methylation in the promoter region of the dopamine D2 receptor (D2R) and reciprocally increased mRNA and protein levels of D2R in the striatum, but not in the hypothalamus. [1] γ-Oryzanol significantly decreased the expression (mRNA and protein) and activity (SAH formation) of DNMTs (DNMT1, DNMT3a, DNMT3b) in the striatum but not in the hypothalamus of HFD-fed mice. [1] γ-Oryzanol decreased the augmented expression of Ccl2, Chop, Dnajb9 and Xbp1s exclusively in the hypothalamus but not in the striatum of HFD-fed mice. [1] |
| Enzyme Assay |
The DNMT enzymatic activity assay was performed using a commercial kit. To assess the inhibitory activity of each compound on DNA methylation, the formation of S-adenosyl-L-homocysteine (SAH) was measured in the presence of each compound (20 μmol/l for screening assays), S-adenosyl methionine (SAM; 10 μmol/l) and DNMT substrate (4 ng/μl) at 37°C for 90 min. For Michaelis-Menten kinetics, DNMT1 (20 μmol/l) was incubated with γ-oryzanol, SAM (5 μmol/l) and the indicated concentration of poly dl-dC at 37°C for 90 min. DNMT3a (100 μmol/l) and DNMT3b (100 μmol/l) were incubated with γ-oryzanol, SAM (5 μmol/l) and the indicated concentration of poly dG-dC at 37°C for 120 min. Extracted protein (0.75 mg/ml) was incubated with SAM (5 μmol/l), poly dl-dC (5 mg/ml), and poly dG-dC (5 mg/ml) at 40°C for 120 min, and SAH formation was measured. Assays were performed in quadruplicate. [1]
The potential antagonistic activity of γ-oryzanol on ERRγ was assessed using a reporter assay system. Non-human mammalian reporter cells constitutively expressing active ERRγ were exposed to the indicated concentrations of each compound for 24 h in triplicate. [1] |
| Cell Assay |
Non-human mammalian reporter cells constitutively expressing active ERRγ were exposed to the indicated concentrations of γ-oryzanol for 24 h in triplicate. ERRγ activity was measured as relative luciferase units. γ-Oryzanol partially decreased ERRγ activity (approximately 40% reduction of the innate value). [1]
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| Animal Protocol |
Seven-week-old male C57BL/6J mice were housed (3-4 per cage) under a 12 h/12 h light/dark cycle at 24°C. After a week of acclimatisation, 8-week-old mice were weight-matched and divided into groups. Mice were allowed free access to food and water. [1]
For the food choice test, γ-oryzanol was administrated to 8-week-old mice by gavage. For other experiments, an HFD containing 0.4% γ-oryzanol was manufactured as pellets. After 12 weeks of feeding, tissue was collected from the striatum and hypothalamus. The daily intake of γ-oryzanol, estimated from the mean food intake of the mice, was approximately 320 μg/g body weight. [1] 5-Aza-2'-deoxycytidine (5-aza-dC) was intraperitoneally injected (0.25 μg/g body weight) three times a week for 12 weeks. [1] To evaluate preference for dietary fat, food tests provided a choice between chow and HFD. Mice were allowed free access to chow and HFD. Intakes of chow and HFD were measured weekly and HFD preference was calculated according to the formula: HFD preference = [(HFD intake/total food intake) × 100]. [1] |
| References | |
| Additional Infomation |
γ-Oryzanol (TN) is a triterpenoid compound. It has been reported to exist in rice (Oryza sativa), cordyceps (Ophiocordyceps sinensis), and other organisms with relevant data.
γ-Oryzanol is a brown rice-specific component. The study demonstrates that γ-oryzanol acts as a potent DNMT inhibitor in the striatum of mice, thereby attenuating the preference for an HFD via the epigenetic modulation of striatal D2R. γ-Oryzanol decreased the levels and activities of DNMTs preferentially in the striatum, with a consequent decrease in DNA methylation in the promoter region of D2R. The inhibitory activity of γ-oryzanol against DNMTs was stronger than that of its metabolite ferulic acid, suggesting the importance of the complete structure for its inhibitory action. γ-Oryzanol also acts as a partial antagonist against ERRγ, which is a positive regulator for DNMT1 production and is highly expressed in the striatum. The study highlights γ-oryzanol as a promising anti-obesity substance with the distinct property of being a novel epigenetic modulator. [1] |
| Molecular Formula |
C40H58O4
|
|---|---|
| Molecular Weight |
602.8861
|
| Exact Mass |
602.433
|
| CAS # |
11042-64-1
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| PubChem CID |
5282164
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| Appearance |
White to off-white solid powder
|
| Density |
1.1±0.1 g/cm3
|
| Boiling Point |
663.2±40.0 °C at 760 mmHg
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| Melting Point |
135-137°C
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| Flash Point |
193.8±20.8 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
|
| Index of Refraction |
1.570
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| LogP |
12.85
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
44
|
| Complexity |
1150
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| Defined Atom Stereocenter Count |
9
|
| SMILES |
C[C@H](CCC=C(C)C)[C@H]1CC[C@@]2([C@@]1(CC[C@]34[C@H]2CC[C@@H]5[C@]3(C4)CC[C@@H](C5(C)C)OC(=O)/C=C/C6=CC(=C(C=C6)O)OC)C)C
|
| InChi Key |
FODTZLFLDFKIQH-FSVGXZBPSA-N
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| InChi Code |
InChI=1S/C40H58O4/c1-26(2)10-9-11-27(3)29-18-20-38(7)33-16-15-32-36(4,5)34(19-21-39(32)25-40(33,39)23-22-37(29,38)6)44-35(42)17-13-28-12-14-30(41)31(24-28)43-8/h10,12-14,17,24,27,29,32-34,41H,9,11,15-16,18-23,25H2,1-8H3/b17-13+/t27-,29-,32+,33+,34+,37-,38+,39-,40+/m1/s1
|
| Chemical Name |
[(1S,3R,6S,8R,11S,12S,15R,16R)-7,7,12,16-tetramethyl-15-[(2R)-6-methylhept-5-en-2-yl]-6-pentacyclo[9.7.0.01,3.03,8.012,16]octadecanyl] (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
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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 |
| 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) |
DMSO : ~62.5 mg/mL (~103.67 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.45 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 20.8 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: 2.08 mg/mL (3.45 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 heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (4.15 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: 10 mg/mL (16.59 mM) in 10% PEG400 10% Tween80 80%saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6587 mL | 8.2934 mL | 16.5868 mL | |
| 5 mM | 0.3317 mL | 1.6587 mL | 3.3174 mL | |
| 10 mM | 0.1659 mL | 0.8293 mL | 1.6587 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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