牛磺熊去氧胆酸钠作用机制 - Medchemexpress - MCE中国

1、Product Data SheetTauroursodeoxycholate SodiumCat. No.: HY-19696ACAS No.: 35807-85-3分式: CHNNaOS分量: 521.69作靶点: ERK; Caspase作通路: MAPK/ERK Pathway; Stem Cell/Wnt; Apoptosis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 H2O : 100 mg/mL (191.68 mM; Need ultrasonic)DMSO :

2、100 mg/mL (191.68 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.9168 mL 9.5842 mL 19.1685 mL5 mM 0.3834 mL 1.9168 mL 3.8337 mL10 mM 0.1917 mL 0.9584 mL 1.9168 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，-

3、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 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: 2.5 mg/mL (4.79 mM); Clear solution此案可获

4、得 2.5 mg/mL (4.79 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/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: 2.5 mg/mL (4.79 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (4.79 mM，饱和度未知) 的

5、澄清溶液。以 1 mL 作液为例，取 100 L 25.0 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: 2.5 mg/mL (4.79 mM); Clear solution此案可获得 2.5 mg/mL (4.79 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 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性

6、 Tauroursodeoxycholate Sodium种内质应激抑制剂。Tauroursodeoxycholate 显著降低凋亡分如 caspase-3 和caspase-12 表达。Tauroursodeoxycholate 也抑制 ERK。IC & Target ERK Caspase-3 Caspase-12体外研究 Tauroursodeoxycholate (TUDCA) suppresses both viability and migration of vascular smooth muscle cells (VSMCs)through inhibition of ERK

7、phosphorylation, by induction of mitogen-activated protein kinase phosphatase-1 (MKP-1)via PKC. Tauroursodeoxycholate inhibits both the proliferation and migration of VSMCs via inhibition of ERK,through Ca2+-dependent PKC translocation. Tauroursodeoxycholate prevents platelet-derived growth factor (

8、PDGF)and vascular injury-induced MMP-9 expression. The knock-down of MKP-1 using specific si-RNA restores the reducedVSMC viability by Tauroursodeoxycholate (200 M), which suggests that anti-proliferative effect ofTauroursodeoxycholate depended on the MKP-1 expression1.体内研究 The effects of Tauroursod

9、eoxycholate (TUDCA) on proliferation and apoptosis of VSMCs in vivo are examined usingimmunohistochemistry for proliferating cell nuclear antigen (PCNA) and the transferase dUTP nick-end labelling (TUNEL) assay. Tauroursodeoxycholate (10, 50, and 100 mg/kg) increases the caspase 3 activity of injure

10、d tissues in adose-dependent manner, indicating that Tauroursodeoxycholate induces apoptosis of VSMCs in the neointima. Usingthe injured tissues, further examination and comparison of the phosphorylation level of ERK and MMP-9 expression isperformed at 1 week after injury, compared with normal contr

11、ols. Balloon injury increased both the phosphorylationof ERK and expression of MMP-9 in the tissues. Tauroursodeoxycholate (10, 50, and 100 mg/kg) inhibitsphosphorylation of ERK and MMP-9 expression in a dose-dependent manner1. Tauroursodeoxycholate (TUDCA) is ahydrophilic bile acid. Tauroursodeoxyc

12、holate as a cytoprotective agent improves liver function and can preventhepatocellular carcinoma by reducing ER stress and apoptosis. Tauroursodeoxycholate significantly reducesexpression of apoptosis molecules, such as caspase-3, caspase-12, C/EBP homologous protein, c-Jun N-terminalkinase (JNK), a

13、ctivating transcription factor 4 (ATF4), X-box binding protein (XBP), and eukaryotic initiation factor 2 (eIF2) in Ang II induced ApoE-/- mice (p0.05) and total cholesterol levels (663.688.7 mg/dL vs 655.765.4 mg/dL; p0 .05) donot differ between the AAA model group and Tauroursodeoxycholate group. I

14、n addition, maximum aortic diameter issignificantly smaller in those in Tauroursodeoxycholate group compared with those in the AAA model group(0.950.03 mm vs 1.790.04 mm; p0.05). AAA lesion areas are also smaller in those in Tauroursodeoxycholate groupthan in those in the AAA model group (0.370.03 m

15、m2 vs 1.510.06 mm2; p0.05)2.PROTOCOLCell Assay 1 Cell viability and proliferation are measured using Ez-Cytox. VSMCs (5103 cells) are seeded onto 96-well plates inPage 2 of 3 www.MedChemESmooth Muscle Cell Growth Medium 2 (SMCGM2) and cultured. After serum starvation, Tauroursodeoxycholate (0,50, 10

16、0, and 200 M) is added to the hVSMCs, with or without 1,2-bis(o-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA, 10 M) and 7-hydroxystaurosporine (H7, 10 M) and cultured for24 h. To assess the effect of Tauroursodeoxycholate on the PDGF-stimulated hVSMC proliferation,

17、 hVSMCs areseeded onto 96-well plates and cultured. After serum starvation, Tauroursodeoxycholate (0, 50, 100, and 200 M) isadded to the hVSMCs, with or without PDGF-BB (50 ng/mL) and cultured. After addition of 10 L of Ez-Cytox intoeach well, cell viability is evaluated by measuring the optical den

18、sity at 450 nm1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats1Administration 12 Sprague-Dawley rats are anaesthetized with a combined anaesthetic (Ketamine, 70 mg/kg; Xylazine, 7 mg/kg ip).Tauroursodeoxycholate is administered orally once

19、a day, in different concentrations (i.e. vehicle, 10, 50, and 100mg/kg) for 2 weeks. The carotid arteries are fixed by perfusion with 4% formaldehyde, then the tissues are embeddedin paraffin, and sections (8 m) are stained with H&E1.Mice2Thirty ApoE-/- C57BL/6 male mice aged 8 weeks are randomly di

20、vided into three groups (n=10 in each group): (i)sham operated and injected with physiologic (0.9%) saline as vehicle (normal: group); (ii) mini-osmotic pumps areimplanted subcutaneously into the right flank of ApoE-/- mice to release Ang II (1000 ng/kg/min) over the course of28 days (AAA model grou

21、p); (iii) AAA model mice treated with Tauroursodeoxycholate daily for 4 weeks at a dosageof 0.5 g/kg/day in drinking water (Tauroursodeoxycholate group). Mice are sacrificed after 28 days of Ang II infusion2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Br J Pharmacol. 2019 Jul;176(13):2162-2178. Cancers (Basel). 2020 Mar 6;12(3). pii: E613. Cell Death Dis. 2020 Apr 24;11(4):279. Front Cell Dev Biol. 2020 May. Biochem Pharmacol. 2018 May 24;154:278-292.Se