γ-谷维素作用机制 - Medchemexpress - MCE中国

1、Product Data Sheet-OryzanolCat. No.: HY-B2194CAS No.: 11042-64-1分式: CHO分量: 602.89作靶点: DNA Methyltransferase作通路: Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 62.5 mg/mL (103.67 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10

2、mgConcentration制备储备液1 mM 1.6587 mL 8.2934 mL 16.5868 mL5 mM 0.3317 mL 1.6587 mL 3.3174 mL10 mM 0.1659 mL 0.8293 mL 1.6587 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro

3、 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.45 mM); Clear solution此案可获得 2.08 mg/mL (3.45 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 m

4、g/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.45 mM); Suspended solution; Need ultrasonic and warmingPage 1 of 2 www.MedChemE此案可获得 2.08 mg/mL (3.45 mM) 的均匀悬浊液，悬浊液可于服和腹腔注射。以 1 mL 作液为例，取

5、 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (3.45 mM); Clear solution此案可获得 2.08 mg/mL (3.45 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 -Oryzanol 有效抑制纹

6、状体中的 DNA 甲基转移酶 (DNMTs)。 抑制 DNMT1 和 DNMT3a，IC50 分别为 3.2 M 和22.3 M。IC & Target DNMT1 DNMT3A3.2 M (IC50) 22.3 M (IC50)体外研究 -Oryzanol significantly inhibits the activities of DNMT1 (IC50=3.2 M), DNMT 3a (IC50=22.3 M) and DNMT 3b(maximum inhibition 57%). In contrast, the inhibitory activity of Ferulic ac

7、id, a metabolite of -Oryzanol, is much lowerthan that of -Oryzanol. Furthermore, -Oryzanol acts as a partial antagonist against ERR, which primarily serves as apositive regulator for DNMT1 production, and consequently decreased the activity of DNMT11.体内研究 The brown rice-specific bioactive component

8、-Oryzanol, a mixture of ferulic acid ester and several phytosterols,attenuates the preference for dietary fat via a decrease in hypothalamic endoplasmic reticulum (ER) stress. -Oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in the striatum of mice. -Oryzanolmight

9、 regulate levels of DNMTs in a striatum-specific manner. -Oryzanol partially decreases ERR activity (anapproximately 40% reduction of the innate value). Oral administration of -Oryzanol to male mice by gavagesignificantly attenuates the preference for an HFD (93% of the values for vehicle-treated mi

10、ce), resulting in anapparent attenuation of body weight gain1.PROTOCOLKinase Assay 1 To assess the inhibitory activity of each compound on DNA methylation, the formation of S-adenosyl-l-homocysteine(SAH) is measured in the presence of each compound (20 M for screening assays),S-adenosyl methionine (

11、SAM; 10M) and DNMT substrate (4 ng/L) at 37C for 90 min. To evaluate the Michaelis-Menten kinetics, DNMT1 (20 M) isincubated with -Oryzanol, SAM (5 M) and the indicated concentration of poly dI-dC at 37C for 90 min. DNMT3a(100 M) and DNMT3b (100 M) are incubated with -Oryzanol, SAM (5 M) and the ind

12、icated concentration of polydGdC at 37C for 120 min. The assays are performed in quadruplicate. Extracted protein (0.75 mg/mL) is incubatedwith SAM (5 M), poly dI-dC (5 g/mL), and poly dGdC (5 g/mL) at 40C for 120 min, and SAH formation ismeasured1.MCE has not independently confirmed the accuracy of

13、 these methods. They are for reference only.Animal Mice1Administration 1 Seven-week-old male C57BL/6J mice are used. To evaluate the preference for the HFD, -Oryzanol is administrated to8-week-old mice by gavage during the food choice test. For the other experiments, an HFD containing 0.4% -Oryzanol

14、 is manufactured as pellets. After 12 weeks of feeding, tissue is collected from the striatum andhypothalamus. The daily intake of -Oryzanol, estimated from the mean food intake of the mice, is approximately320 g/g body weight. The doses of -Oryzanol are determined.Page 2 of 3 www.MedChemEMCE has no

15、t independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Kozuka C, et al. Impact of brown rice-specific -oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-inducedobesity in mice. Diabetologia. 2017 Aug;60(8):1502-15