Arglabin
(Synonyms: 阿格拉宾; (+)-Arglabin) 目录号 : GC35385
A sesquiterpene lactone
Cas No.:84692-91-1
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
Arglabin is a sesquiterpene γ-lactone originally isolated from A. glabella that has anticancer and anti-inflammatory activities.1 It inhibits the growth of LS-180, SSC-4, HeLa, MCF-7, and HL-60 cancer cells (IC50s = 20, 10, 20, 20, and 50 ?M, respectively).2 Arglabin reduces tumor growth in an SCC-4 mouse xenograft model when administered at a dose of 40 ?g/g. It is a selective inhibitor of the NLRP3 inflammasome over the NLRP1, AIM2, and NLRC4 inflammasomes when used at a concentration of 50 nM.1 Arglabin (50 nM) reduces increases in protein levels of NLRP3, caspase-1, IL-1β, and IL-18 induced by cholesterol crystals in LPS-primed mouse peritoneal macrophages. It decreases plasma levels of IL-1β, oxidized LDL autoantibodies, total cholesterol, and triglycerides, and reduces the size of atherosclerotic lesions in the aorta of mice fed a high-fat diet when administered at a dose of 2.5 ng/g.
1.Abderrazak, A., Couchie, D., Mahmood, D.F.D., et al.Anti-inflammatory and antiatherogenic effects of the NLRP3 inflammasome inhibitor arglabin in ApoE2.Ki mice fed a high-fat dietCirculation131(12)1061-1070(2015) 2.He, W., Lai, R., Lin, Q., et al.Arglabin is a plant sesquiterpene lactone that exerts potent anticancer effects on human oral squamous cancer cells via mitochondrial apoptosis and downregulation of the mTOR/PI3K/Akt signaling pathway to inhibit tumor growth in vivoJ. BUON23(6)1679-1685(2018)
| Cas No. | 84692-91-1 | SDF | |
| 别名 | 阿格拉宾; (+)-Arglabin | ||
| Canonical SMILES | C[C@]1(CC[C@](C2=C)([H])[C@@](OC2=O)([H])[C@@]3([H])C(C)=CC4)[C@]34O1 | ||
| 分子式 | C15H18O3 | 分子量 | 246.3 |
| 溶解度 | DMSO: ≥ 100 mg/mL (406.01 mM) | 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 | 4.0601 mL | 20.3004 mL | 40.6009 mL |
| 5 mM | 0.812 mL | 4.0601 mL | 8.1202 mL |
| 10 mM | 0.406 mL | 2.03 mL | 4.0601 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。
Arglabin could target inflammasome-induced ARDS and cytokine storm associated with COVID-19
Mol Biol Rep 2021 Dec;48(12):8221-8225.PMID:34655016DOI:10.1007/s11033-021-06827-7.
Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1β and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like Arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.
Arglabin: From isolation to antitumor evaluation
Chem Biol Interact 2015 Oct 5;240:180-98.PMID:26327249DOI:10.1016/j.cbi.2015.08.015.
Arglabin belongs to guaianolide class of sesquiterpene lactones, isolated from Artemisia species. The molecule bears a 5,7,5-tricyclic ring system having five contiguous stereo centers in which the two five membered rings are trans-annulated. Arglabin shows promising antitumor activity against different tumor cell lines. The antitumor activity of Arglabin proceeds through its inhibition of farnesyl transferase which leads to the activation of RAS proto-oncogene, a process that is believed to play a pivotal role in 20-30% of all human tumors. It actually inhibits the incorporation of farnesyl pyrophosphate into human H-ras proteins by the enzyme farnesyl transferase (FTase). The present review is an attempt to summarize the chemistry and biology of this molecule since its isolation in 1982. It embodies the isolation, structure elucidation, stereo chemical description, structural classification, chemical synthesis, structural modifications and antitumor evaluation reported till date.
Analysis of Arglabin and its derivatives using high-performance liquid chromatography
Phytochem Anal 2021 Sep;32(5):780-784.PMID:33410214DOI:10.1002/pca.3023.
Introduction: The chemical modification of Arglabin, a natural sesquiterpene lactone, has garnered significant attention because it comprises a guaianolide structure that exhibits antitumour and immunomodulating properties. Its primarily derived from Artemisia glabella Kar. et Kir. Physicochemical characterisation of commercial anititumour drugs based on Arglabin can be time-consuming and expensive; thus, high-performance liquid chromatography (HPLC) is an optimal method to identify Arglabin and its derivatives. Aim: This study has a two-fold objective: to develop a unified HPLC method for quality control of Arglabin and its new hybrid molecules with alkaloids (cytisine, anabasine), and to study the relationship between their structures and chromatographic behaviours. Materials and methods: To develop a selective method that ensures the quality of Arglabin and its derivatives, HPLC was used with the Zorbax SB-C18 analytical column. Dipole moments were calculated via the restricted Hartree-Fock method (RHF/6-31G(d, p)) and the B3LYР density functional theory with full geometry optimisation by using the GAUSSIAN 03 W program. Results: A novel analytical method has been developed using reversed-phase (RP) HPLC, which is selective and allows reliable as well as quantitative determination of Arglabin and its derivatives. To confirm the selectivity of the developed method, the chromatographic capacity factors and column selectivity were calculated. The relationship between retention time and structure (particularly, the nature of the substituent) was studied for the first time for Arglabin and its derivatives using the B3LYP/6-31G(d) quantum chemical method. The influence of the dipole moment on the retention time of Arglabin and its derivatives was confirmed. Conclusion: A novel unified quality control method using HPLC was developed to analyse Arglabin, and its new hybrid molecules with alkaloids (cytisine and anabasine). For the first time, the relationship between the chromatographic behaviour in RP-HPLC and the dipole moment for Arglabin and its derivatives was revealed.
Single-Cell Reconstruction of Progression Trajectory Reveals Intervention Principles in Pathological Cardiac Hypertrophy
Circulation 2020 May 26;141(21):1704-1719.PMID:32098504DOI:10.1161/CIRCULATIONAHA.119.043053.
Background: Pressure overload-induced pathological cardiac hypertrophy is a common predecessor of heart failure, the latter of which remains a major cardiovascular disease with increasing incidence and mortality worldwide. Current therapeutics typically involve partially relieving the heart's workload after the onset of heart failure. Thus, more pathogenesis-, stage-, and cell type-specific treatment strategies require refined dissection of the entire progression at the cellular and molecular levels. Methods: By analyzing the transcriptomes of 11,492 single cells and identifying major cell types, including both cardiomyocytes and noncardiomyocytes, on the basis of their molecular signatures, at different stages during the progression of pressure overload-induced cardiac hypertrophy in a mouse model, we characterized the spatiotemporal interplay among cell types, and tested potential pharmacological treatment strategies to retard its progression in vivo. Results: We illustrated the dynamics of all major cardiac cell types, including cardiomyocytes, endothelial cells, fibroblasts, and macrophages, as well as those of their respective subtypes, during the progression of disease. Cellular crosstalk analysis revealed stagewise utilization of specific noncardiomyocytes during the deterioration of heart function. Specifically, macrophage activation and subtype switching, a key event at middle-stage of cardiac hypertrophy, was successfully targeted by Dapagliflozin, a sodium glucose cotransporter 2 inhibitor, in clinical trials for patients with heart failure, as well as TD139 and Arglabin, two anti-inflammatory agents new to cardiac diseases, to preserve cardiac function and attenuate fibrosis. Similar molecular patterns of hypertrophy were also observed in human patient samples of hypertrophic cardiomyopathy and heart failure. Conclusions: Together, our study not only illustrated dynamically changing cell type crosstalk during pathological cardiac hypertrophy but also shed light on strategies for cell type- and stage-specific intervention in cardiac diseases.
Arglabin, an EGFR receptor tyrosine kinase inhibitor, suppresses proliferation and induces apoptosis in prostate cancer cells
Biomed Pharmacother 2022 Dec;156:113873.PMID:36272260DOI:10.1016/j.biopha.2022.113873.
Evidence for clinical efficacy of a semisynthetic derivative of Arglabin in anticancer treatment prompted us to examine molecular mechanisms and cellular targets of Arglabin. Arglabin, a sesquiterpene lactone isolated from Artemisia glabella was cytotoxic to different human cancer cell lines including those derived from advanced triple-negative breast, lung, androgen-dependent and androgen-independent prostate carcinomas. Noteworthy, Arglabin was less toxic to non-neoplastic prostate epithelial cells indicating selectivity for cancer cells. At the molecular level, prior to any biochemical signs of cellular toxicity, Arglabin reduced levels of cell-surface sulphanyl groups and inhibited phosphorylation of the redox-sensitive receptor tyrosine kinase EGFR, the only active RTK in PC-3 prostate cancer cells among 49 TRKs analyzed by the assay. Henceforth, Arglabin inhibited the EGFR downstream signaling pathways mTORC1 and mTORC2. Accordingly, Arglabin induced autophagosome formation and autophagic flux, inhibited phosphorylation of ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and impeded cell cycle progression and proliferation of PC-3 cells. In agreement with inhibition of the mTORC2 pathway, Arglabin induced sustained actin polymerization, inhibited cell migration, and triggered apoptosis in vitro in 2D cell culture and colony formation assay and in vivo in prostate cancer xenografts grown on chick chorioallantoic membranes. Under physiological conditions, Arglabin rapidly formed adducts with reduced glutathione (GSH). Moreover, thiol-based antioxidants GSH and β-mercaptoethanol abolished arglabin-induced cancer cell toxicity, whereas the non-thiol antioxidant trolox was ineffective pointing to a crucial role of interaction with cell-surface sulphanyl groups for Arglabin cytotoxic activity against cancer cells.