γ-谷維素作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data Sheet-OryzanolCat. No.: HY-B2194CAS No.: 11042-64-1分式: CHO分量: 602.89作靶點(diǎn): DNA Methyltransferase作通路: Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 62.5 mg/mL (103.67 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10

2、mgConcentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro

3、 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.45 mM); Clear solution此案可獲得 2.08 mg/mL (3.45 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 m

4、g/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 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此案可獲得 2.08 mg/mL (3.45 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取

5、 100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (3.45 mM); Clear solution此案可獲得 2.08 mg/mL (3.45 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 -Oryzanol 有效抑制紋

6、狀體中的 DNA 甲基轉(zhuǎn)移酶 (DNMTs)。 抑制 DNMT1 和 DNMT3a，IC50 分別為 3.2 M 和22.3 M。IC & Target DNMT1 DNMT3A3.2 M (IC50) 22.3 M (IC50)體外研究 -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.體內(nèi)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