Biliatresone
目录号 : GC61611
Biliatresone是一种从球藻Dysphaniaglomulifera和D.littoralis中分离出来的天然毒素。Biliatresone是一种1,2-二芳基-2-丙酮类异黄酮，在斑马鱼模型中会产生肝外胆道闭锁。
Cas No.:1801433-90-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Biliatresone is a natural toxin isolated from Dysphania glomulifera and D. littoralis. Biliatresone, a 1,2-diaryl-2-propenone class of isoflavonoid, produces extrahepatic biliary atresia in a zebrafish model[1].
Biliatresone has a reduction in primary cilia and a dose-dependent decrease in visible microtubules, suggesting that Biliatresone decreases microtubule stability in primary neonatal mouse extrahepatic cholangiocytes[1]. Biliatresone (2 µg/ml; for 24 hours) shows disruption of the spheroid lumen and abnormal cholangiocyte polarity in mouse cholangiocyte[1].
Biliatresone exhibits toxicity at doses of 0.065-1.0 μg/mL with a marked reduction and the lethal dose of Biliatresone in a zebrafish assay is 1 μg/mL[1]. Larvae treated at 5 dpf with low doses of biliatresone [0.0625 µg/ml (0.2 µM) and 0.125 µg/ml (0.4 µM)] shows only subtle gallbladder defects, whereas larvae treated with higher doses has pronounced morphological defects of the gallbladder and extrahepatic ducts[1].
[1]. Kyung A Koo, et al. Biliatresone, a Reactive Natural Toxin From Dysphania Glomulifera and D. Littoralis: Discovery of the Toxic Moiety 1,2-Diaryl-2-Propenone. Chem Res Toxicol. 2015 Aug 17;28(8):1519-21. [2]. Kristin Lorent, et al. Identification of a Plant Isoflavonoid That Causes Biliary Atresia. Sci Transl Med. 2015 May 6;7(286):286ra67.
| Cas No. | 1801433-90-8 | SDF | |
| Canonical SMILES | C=C(C(C1=C(C=C2OCOC2=C1OC)OC)=O)C3=CC=CC=C3O | ||
| 分子式 | C18H16O6 | 分子量 | 328.32 |
| 溶解度 | 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 | 3.0458 mL | 15.229 mL | 30.4581 mL |
| 5 mM | 0.6092 mL | 3.0458 mL | 6.0916 mL |
| 10 mM | 0.3046 mL | 1.5229 mL | 3.0458 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。
Biliatresone: progress in biliary atresia study
World J Pediatr 2022 Sep 27.PMID:36166189DOI:10.1007/s12519-022-00619-0.
Background: Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis and treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current theorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still largely unknown. Recently, Biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we summarized the latest progress of Biliatresone research in BA and tried to answer the question of whether it could provide further clues to the etiology of human BA. Data sources: We conducted a PubMed search for any published articles related to the topic using search terms including "biliary atresia", "Biliatresone", "GSH", and "HSP90". Relevant data were extracted from the original text or supplementary materials of the corresponding articles. Results: Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors involved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epidemiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occurrence of biliary atresia is partly due to Biliatresone or its structure-like compounds depositing in human body via vegetables or/and the altered intestinal flora structure can be tentatively established. Conclusions: Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA, and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered intestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. However, the evidence from large sample epidemiological research is necessary.
Biliary Atresia: Clinical and Research Challenges for the Twenty-First Century
Hepatology 2018 Sep;68(3):1163-1173.PMID:29604222DOI:10.1002/hep.29905.
Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a prenatal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g., Biliatresone) and of viruses (e.g., cytomegalovirus) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate proinflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE. (Hepatology 2018; 00:000-000).
The synthetic toxin Biliatresone causes biliary atresia in mice
Lab Invest 2020 Nov;100(11):1425-1435.PMID:32681026DOI:10.1038/s41374-020-0467-7.
Exposure to environmental toxins may be responsible for biliary atresia. The focus of this study was to investigate the effect of Biliatresone on the development of the hepatobiliary system in mice. We successfully synthesized Biliatresone with a purity of 98% and confirmed its biliary toxicity. Exposure to high doses of Biliatresone caused abortion or death in pregnant mice. Neonatal mice injected with Biliatresone developed clinical signs of biliary obstruction, and dysplasia or the absence of extrahepatic biliary tract lumen, which confirmed the occurrence of biliary atresia. In the portal tract of biliary atresia mice, signs of infiltration of inflammatory cells and liver fibrosis were observed. The signature of extrahepatic biliary gene expression in these mice mainly involved the cell adhesion process, and hepatic RNA-seq was highly linked to transcriptional evidence of oxidative stress. When compared with the control group, hepatic glutathione levels were markedly reduced after Biliatresone injection. Taken together, these data confirm that Biliatresone causes severe developmental abnormalities of the hepatobiliary system in mice. Furthermore, decreased levels of glutathione may play a mechanistic role in the pathogenesis of liver fibrosis in biliatresone-induced experimental biliary atresia.
Reactivity of Biliatresone, a Natural Biliary Toxin, with Glutathione, Histamine, and Amino Acids
Chem Res Toxicol 2016 Feb 15;29(2):142-9.PMID:26713899DOI:10.1021/acs.chemrestox.5b00308.
In our previous work, we identified a natural toxin, Biliatresone, from Dysphania glomulifera and D. littoralis, endemic plants associated with outbreaks of biliary atresia in Australian neonatal livestock. Biliatresone is a very rare isoflavonoid with an α-methylene ketone between two phenyls, 1,2-diaryl-2-propenone, along with methylenedioxy, dimethoxyl, and hydroxyl functional groups, that causes extrahepatic biliary toxicity in zebrafish. The toxic core of Biliatresone is a methylene in the α-position relative to the ketone of 1,2-diaryl-2-propenone that serves as an electrophilic Michael acceptor. The α-methylene of Biliatresone spontaneously conjugated with water and methanol (MeOH), respectively, via Michael addition in a reverse phase high-performance liquid chromatography (RP-HPLC) analysis. We here report the reactivity of Biliatresone toward glutathione (GSH), several amino acids, and other thiol- or imidazole-containing biomolecules. LC-MS and HPLC analysis of the conjugation reaction showed the reactivity of Biliatresone to be in the order histidine > N-acetyl-d-cysteine (D-NAC) = N-acetyl-l-cysteine (L-NAC) > histamine > glutathione ≥ cysteine ≫ glycine > glutamate > phenylalanine, while serine and adenine had no reactivity due to intramolecular hydrogen bonding in the protic solvents. The reactivity of ethyl vinyl ketone (EVK, 1-penten-3-one), an example of a highly reactive α,ß-unsaturated ketone, toward GSH gave a 6.7-fold lower reaction rate constant than that of Biliatresone. The reaction rate constant of synthetic 1,2-diaryl-2-propen-1-one (DP), a core structure of the toxic molecule, was 10-fold and 1.5-fold weaker in potency compared to the reaction rate constants of Biliatresone and EVK, respectively. These results demostrated that the methylenedioxy, dimethoxyl, and hydroxyl functional groups of Biliatresone contribute to the stronger reactivity of the Michael acceptor α-methylene ketone toward nucleophiles compared to that of DP and EVK.
Biliatresone, a Reactive Natural Toxin from Dysphania glomulifera and D. littoralis: Discovery of the Toxic Moiety 1,2-Diaryl-2-Propenone
Chem Res Toxicol 2015 Aug 17;28(8):1519-21.PMID:26175131DOI:10.1021/acs.chemrestox.5b00227.
We identified a reactive natural toxin, Biliatresone, from Dysphania glomulifera and D. littoralis collected in Australia that produces extrahepatic biliary atresia in a zebrafish model. Three additional isoflavonoids, including the known isoflavone betavulgarin, were also isolated. Biliatresone is in the very rare 1,2-diaryl-2-propenone class of isoflavonoids. The α-methylene of the 1,2-diaryl-2-propenone of Biliatresone spontaneously reacts via Michael addition in the formation of water and methanol adducts. The lethal dose of Biliatresone in a zebrafish assay was 1 μg/mL, while the lethal dose of synthetic 1,2-diaryl-2-propen-1-one was 5 μg/mL, suggesting 1,2-diaryl-2-propenone as the toxic Michael acceptor.