Eupalinolide B
(Synonyms: 野马追内酯B) 目录号 : GC38608
Eupalinolide B 是从 Eupatorium lindleyanum 分离的胚芽倍半萜。 Eupalinolide B 对 A-549，BGC-823 和 HL-60 等肿瘤细胞具有细胞毒性。
Cas No.:877822-41-8
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
Eupalinolide B is a germacrane sesquiterpene isolated from Eupatorium lindleyanum. Eupalinolide B demonstrates potent cytotoxicity against A-549, BGC-823 and HL-60 tumour cell lines[1].
[1]. Yang NY, et al. Cytotoxic sesquiterpene lactones from Eupatorium lindleyanum. J Asian Nat Prod Res. 2007 Apr-Aug;9(3-5):339-45.
| Cas No. | 877822-41-8 | SDF | |
| 别名 | 野马追内酯B | ||
| Canonical SMILES | O=C(O[C@@H]1C/C(COC(C)=O)=C/C[C@H](OC(C)=O)/C(C)=C/[C@@]([C@]1([H])C2=C)([H])OC2=O)/C(C)=C/CO | ||
| 分子式 | C24H30O9 | 分子量 | 462.49 |
| 溶解度 | Soluble in DMSO | 储存条件 | -20°C, protect from light |
| 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 | 2.1622 mL | 10.811 mL | 21.6221 mL |
| 5 mM | 0.4324 mL | 2.1622 mL | 4.3244 mL |
| 10 mM | 0.2162 mL | 1.0811 mL | 2.1622 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。
Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway
Acta Biochim Biophys Sin (Shanghai) 2022 Jul 25;54(7):974-986.PMID:35866605DOI:10.3724/abbs.2022082.
Primary hepatic carcinoma is a common malignant tumor. The classic molecular targeted drug sorafenib is costly and is only effective for some patients. Therefore, it is of great clinical significance to search for new molecular targeted drugs. Eupalinolide B (EB) from Eupatorium lindleyanum DC. is used to treat chronic tracheitis in clinical practice. However, the role of EB in hepatic carcinoma is unknown. In this study, we first measure the effect of EB on tumor growth in a xenograft model and PDX model. The cell proliferation and migration are also detected in human hepatocarcinoma cell lines (SMMC-7721 and HCCLM3). Then, we investigate cell cycle, cell apoptosis, cell necrosis, cell autophagy, and ferroptosis by flow cytometry, western blot analysis and electron microscopy. The results demonstrate that EB exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. When HO-1 is inhibited, EB-induced cell death and ER protein expression are rescued. The migration-related mechanism consists of activation of the ROS-ER-JNK signaling pathway and is not connected to ferroptosis. In summary, we first discover that EB inhibits cell proliferation and migration in hepatic carcinoma, and thus EB is a promising anti-tumor compound that can be used for hepatic carcinoma.
Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy
Sci Adv 2022 Aug 12;8(32):eabo0789.PMID:35947662DOI:10.1126/sciadv.abo0789.
Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule Eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.
Eupalinolide B attenuates lipopolysaccharide-induced acute lung injury through inhibition of NF-κB and MAPKs signaling by targeting TAK1 protein
Int Immunopharmacol 2022 Oct;111:109148.PMID:35988521DOI:10.1016/j.intimp.2022.109148.
Acute lung injury (ALI) is a life-threatening disease characterized by severe inflammatory response, which has no pharmacological therapy in clinic. In this study, we found that Eupalinolide B (EB), a sesquiterpene lactone isolated from Eupatorium lindleyanum, significantly ameliorated lipopolysaccharide (LPS)-induced ALI in mice, which manifests as reduction in lung injury score, activity of myeloperoxidase, and release of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). In RAW264.7 murine macrophages, EB effectively inhibited LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) by down-regulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), respectively. Mechanistically, EB not only blocked LPS-induced phosphorylation of inhibitor of nuclear factor kappa B kinase-α/β (IKKα/β), phosphorylation and degradation of inhibitor of nuclear factor-kappa B alpha (IκBα), and phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB) P65, but also suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in vitro or in vivo. Through cellular thermal shift assay and western blotting, EB was demonstrated to target and inactivate transforming growth factor β activated kinase-1 (TAK1), which is an important upstream kinase for the activation of NF-κB and MAPKs pathways. Additionally, EB-mediated actions were markedly abolished by dithiothreitol in LPS-exposed RAW264.7 cells, suggesting a crucial role of the α,γ-unsaturated lactone for the anti-inflammatory activity of EB. In conclusion, our findings showed that EB could effectively alleviate ALI in mice, and attenuate inflammatory response by inhibiting the activation of TAK1, and TAK1-mediated activation of NF-κB and MAPKs cascades.
Pharmacokinetics of eupalinolide A, Eupalinolide B and hyperoside from Eupatorium lindleyanum in rats by LC/MS/MS
J Chromatogr B Analyt Technol Biomed Life Sci 2015 Jul 15;995-996:1-7.PMID:26011510DOI:10.1016/j.jchromb.2015.04.038.
A simple, selective, and sensitive LC/MS/MS method was developed and validated for simultaneous determination of eupalinolide A, Eupalinolide B, and hyperoside in rat plasma. Plasma samples were processed by protein precipitation with acetonitrile. The three analytes, together with internal standard (IS, lysionotin), were separated on a Venusil MP-C18 column (50mm×2.1mm, 3μm) using a mobile phase of methanol and 10mM ammonium acetate (45:55, v/v) with isocratic elution. Mass spectrometric detection was performed by multiple-reaction monitoring mode via electrospray ionization source. Linear calibration curves were obtained for the following concentration range: 1.28-640ng/mL for EA; 1.98-990ng/mL for EB; and 2.00-1000ng/mL for HYP. The intra- and inter-day precision was less than 10.25%, and the accuracy was between 89.16% and 110.63%. The extraction recovery of the analytes and IS from rat plasma was above 88.75%. The validated method has been successfully applied to pharmacokinetic studies of the three analytes following intragastric administration of Eupatorium lindleyanum extract at a single dose of 100, 250, and 625mg/kg to Sprague-Dawley rats, respectively. The pharmacokinetic results may help to better understand the pharmacological actions of the herb E. lindleyanum.
Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes
Front Pharmacol 2023 Jan 25;14:1093696.PMID:36762117DOI:10.3389/fphar.2023.1093696.
Eupalinolide A (EA; Z-configuration) and Eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.