Ursodeoxycholic Acid (sodium salt)
(Synonyms: 熊去氧胆酸钠盐; Ursodeoxycholate sodium; Ursodiol sodium; UCDA sodium) 目录号 : GC45132
A secondary bile acid
Cas No.:2898-95-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ursodeoxycholic acid (UDCA) is a secondary bile acid formed via epimerization of chenodeoxycholic acid . UDCA is also a metabolite of lithocholic acid in human liver microsomes. It inhibits taurocholic acid uptake in HeLa cells expressing recombinant sodium/taurocholate cotransporting polypeptide (NTCP) with an IC50 value of 3.6 μM. UDCA (50 μM) inhibits apoptosis induced by deoxycholic acid or ethanol in primary rat hepatocytes. Dietary administration of UDCA blocks DCA-induced increases in the number of TUNEL-positive hepatocytes in rats. Formulations containing UDCA have been used in the treatment of primary biliary cirrhosis.
| Cas No. | 2898-95-5 | SDF | |
| 别名 | 熊去氧胆酸钠盐; Ursodeoxycholate sodium; Ursodiol sodium; UCDA sodium | ||
| Canonical SMILES | [O-]C(CC[C@@H](C)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C)=O.[Na+] | ||
| 分子式 | C24H39O4•Na | 分子量 | 414.6 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 10 mg/ml,Ethanol: 15 mg/ml | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.412 mL | 12.0598 mL | 24.1196 mL |
| 5 mM | 0.4824 mL | 2.412 mL | 4.8239 mL |
| 10 mM | 0.2412 mL | 1.206 mL | 2.412 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Primary biliary cholangitis: pathogenesis and therapeutic opportunities
Nat Rev Gastroenterol Hepatol 2020 Feb;17(2):93-110.PMID:31819247DOI:10.1038/s41575-019-0226-7.
Primary biliary cholangitis is a chronic, seropositive and female-predominant inflammatory and cholestatic liver disease, which has a variable rate of progression towards biliary cirrhosis. Substantial progress has been made in patient risk stratification with the goal of personalized care, including early adoption of next-generation therapy with licensed use of obeticholic acid or off-label fibrate derivatives for those with insufficient benefit from Ursodeoxycholic Acid, the current first-line drug. The disease biology spans genetic risk, epigenetic changes, dysregulated mucosal immunity and altered biliary epithelial cell function, all of which interact and arise in the context of ill-defined environmental triggers. A current focus of research on nuclear receptor pathway modulation that specifically and potently improves biliary excretion, reduces inflammation and attenuates fibrosis is redefining therapy. Patients are benefiting from pharmacological agonists of farnesoid X receptor and peroxisome proliferator-activated receptors. Immunotherapy remains a challenge, with a lack of target definition, pleiotropic immune pathways and an interplay between hepatic immune responses and cholestasis, wherein bile acid-induced inflammation and fibrosis are dominant clinically. The management of patient symptoms, particularly pruritus, is a notable goal reflected in the development of rational therapy with apical sodium-dependent bile acid transporter inhibitors.
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases
J Biomed Sci 2018 Oct 26;25(1):75.PMID:30367658DOI:10.1186/s12929-018-0475-8.
Background: Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis. Main body: The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (Ursodeoxycholic Acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway. Short conclusion: Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.
Fibrates and cholestasis
Hepatology 2015 Aug;62(2):635-43.PMID:25678132DOI:10.1002/hep.27744.
Cholestasis, including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), results from an impairment or disruption of bile production and causes intracellular retention of toxic bile constituents, including bile salts. If left untreated, cholestasis leads to liver fibrosis and cirrhosis, which eventually results in liver failure and the need for liver transplantation. Currently, the only therapeutic option available for these patients is Ursodeoxycholic Acid (UDCA), which slows the progression of PBC, particularly in stage I and II of the disease. However, some patients have an incomplete response to UDCA therapy, whereas other, more advanced cases often remain unresponsive. For PSC, UDCA therapy does not improve survival, and recommendations for its use remain controversial. These considerations emphasize the need for alternative therapies. Hepatic transporters, located along basolateral (sinusoidal) and apical (canalicular) membranes of hepatocytes, are integral determinants of bile formation and secretion. Nuclear receptors (NRs) are critically involved in the regulation of these hepatic transporters and are natural targets for therapy of cholestatic liver diseases. One of these NRs is peroxisome proliferator-activated receptor alpha (PPARα), which plays a central role in maintaining cholesterol, lipid, and bile acid homeostasis by regulating genes responsible for bile acid synthesis and transport in humans, including cytochrome P450 (CYP) isoform 7A1 (CYP7A1), CYP27A1, CYP8B1, uridine 5'-diphospho-glucuronosyltransferase 1A1, 1A3, 1A4, 1A6, hydroxysteroid sulfotransferase enzyme 2A1, multidrug resistance protein 3, and apical sodium-dependent bile salt transporter. Expression of many of these genes is altered in cholestatic liver diseases, but few have been extensively studied or had the mechanism of PPARα effect identified. In this review, we examine what is known about these mechanisms and consider the rationale for the use of PPARα ligand therapy, such as fenofibrate, in various cholestatic liver disorders.
Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis
J Pediatr Gastroenterol Nutr 2002 Aug;35(2):185-91.PMID:12187295DOI:10.1097/00005176-200208000-00015.
Objectives: Rats with ethinyl estradiol-induced cholestasis have a decreased bile flow and a decreased expression of basolateral and canalicular hepatocyte membrane transporters. The bile acid Ursodeoxycholic Acid improves bile flow in these animals. The purpose of this study was to examine the effect of Ursodeoxycholic Acid on the expression of hepatocellular bile acid carriers. Methods: Rats received either ethinyl estradiol (5 mg.kg body wt. for 10 days) or ethinyl estradiol associated with Ursodeoxycholic Acid (1% in the diet). A third group of rats received Ursodeoxycholic Acid alone. Bile flow, bile acid, and glutathione biliary outputs were measured. Messenger RNA levels and protein expression of Na -dependent taurocholate co-transporting polypeptide, and bile salt export pump were determined in basolateral and canalicular membrane preparations by Northern and Western blot analysis. Results: Ursodeoxycholic Acid restored bile flow in ethinyl estradiol-treated rats by increasing bile acid secretion. It did not improve glutathione output nor bile acid-independent flow. Na -dependent taurocholate co-transporting polypeptide mRNA and protein were decreased by ethinyl estradiol and not restored by Ursodeoxycholic Acid. In contrast, canalicular bile salt export pump protein expression was decreased by ethinyl estradiol and fully restored to control levels by Ursodeoxycholic Acid. Conclusions: Ursodeoxycholic Acid increases bile flow in ethinyl estradiol-treated rats by increasing bile acid secretion. This increase is possibly mediated by a normalization of the expression of the canalicular bile salt export pump.
Bile acid signaling and biliary functions
Acta Pharm Sin B 2015 Mar;5(2):123-8.PMID:26579437DOI:10.1016/j.apsb.2015.01.009.
This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5), farnesoid X receptor (FXR), Ursodeoxycholic Acid (UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5-7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.