Tabersonine
(Synonyms: 水甘草碱) 目录号 : GC38169
An indole alkaloid
Cas No.:4429-63-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tabersonine is an indole alkaloid that has been found in the beans of Voacanga.1 It inhibits amyloid-β (1-42) (Aβ42) fibril formation and disintegrates preformed Aβ42 fibrils in vitro when used at a concentration of 10 μM. Tabersonine is an intermediate in the biosynthesis of vindoline, a precursor in the synthesis of anticancer agents.2
1.Kai, T., Zhang, L., Wang, X., et al.Tabersonine inhibits amyloid fibril formation and cytotoxicity of Aβ(1-42)ACS Chem. Neurosci.6(6)879-888(2015) 2.Qu, Y., Easson, M.L.A.E., Froese, J., et al.Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeastProc. Natl. Acad. Sci. USA112(19)6224-6229(2015)
| Cas No. | 4429-63-4 | SDF | |
| 别名 | 水甘草碱 | ||
| Canonical SMILES | O=C(OC)C1=C2NC3=CC=CC=C3[C@@]24CCN5CC=C[C@@]([C@@]45[H])(CC)C1 | ||
| 分子式 | C21H24N2O2 | 分子量 | 336.43 |
| 溶解度 | DMF: 2 mg/ml,DMSO: 2 mg/ml,Ethanol: slightly soluble | 储存条件 | 4°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 | 2.9724 mL | 14.8619 mL | 29.7239 mL |
| 5 mM | 0.5945 mL | 2.9724 mL | 5.9448 mL |
| 10 mM | 0.2972 mL | 1.4862 mL | 2.9724 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。
Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination
Biochem Pharmacol 2018 Aug;154:183-192.PMID:29746822DOI:10.1016/j.bcp.2018.05.004.
Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that Tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that Tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1β. Furthermore, Tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that Tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.
Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in Catharanthus roseus
Plant Physiol 2018 Aug;177(4):1473-1486.PMID:29934299DOI:10.1104/pp.18.00549.
Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (Catharanthus roseus). Lochnericine is derived from the stereoselective C6,C7-epoxidation of Tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, and transient gene inactivation, we identified two highly conserved P450s that efficiently catalyze the epoxidation of Tabersonine: Tabersonine 6,7-epoxidase isoforms 1 and 2 (TEX1 and TEX2). Both proteins are quite divergent from the previously characterized Tabersonine 2,3-epoxidase and are more closely related to Tabersonine 16-hydroxylase, involved in vindoline biosynthesis in leaves. Biochemical characterization of TEX1/2 revealed their strict substrate specificity for Tabersonine and their inability to epoxidize 19-hydroxytabersonine, indicating that they catalyze the first step in the pathway leading to hörhammericine production. TEX1 and TEX2 displayed complementary expression profiles, with TEX1 expressed mainly in roots and TEX2 in aerial organs. Our results suggest that TEX1 and TEX2 originated from a gene duplication event and later acquired divergent, organ-specific regulatory elements for lochnericine biosynthesis throughout the plant, as supported by the presence of lochnericine in flowers. Finally, through the sequential expression of TEX1 and up to four other MIA biosynthetic genes in yeast, we reconstituted the 19-acetylhörhammericine biosynthetic pathway and produced tailor-made MIAs by mixing enzymatic modules that are naturally spatially separated in the plant. These results lay the groundwork for the metabolic engineering of Tabersonine/lochnericine derivatives of pharmaceutical interest.
Tabersonine inhibits amyloid fibril formation and cytotoxicity of Aβ(1-42)
ACS Chem Neurosci 2015 Jun 17;6(6):879-88.PMID:25874995DOI:10.1021/acschemneuro.5b00015.
The misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid fibrils are key events in the amyloid cascade hypothesis for the etiology of Alzheimer's disease (AD). Using thioflavin-T (ThT) fluorescence assay, atomic force microscopy, circular dichroism, size exclusion chromatography, surface plasmon resonance (SPR), and cytotoxicity tests, we demonstrate that Tabersonine, an ingredient extracted from the bean of Voacanga africana, disrupts Aβ(1-42) aggregation and ameliorates Aβ aggregate-induced cytotoxicity. A small amount of Tabersonine (e.g., 10 μM) can effectively inhibit the formation of Aβ(1-42) (e.g., 80 μM) fibrils or convert mature fibrils into largely innocuous amorphous aggregates. SPR results indicate that Tabersonine binds to Aβ(1-42) oligomers in a dose-dependent way. Molecular dynamics (MD) simulations further confirm that Tabersonine can bind to oligomers such as the pentamer of Aβ(1-42). Tabersonine preferentially interact with the β-sheet grooves of Aβ(1-42) containing aromatic and hydrophobic residues. The various binding sites and modes explain the diverse inhibitory effects of Tabersonine on Aβ aggregation. Given that Tabersonine is a natural product and a precursor for vincristine used in cancer chemotherapy, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD.
Optimization of Tabersonine Methoxylation to Increase Vindoline Precursor Synthesis in Yeast Cell Factories
Molecules 2021 Jun 11;26(12):3596.PMID:34208368DOI:10.3390/molecules26123596.
Plant specialized metabolites are widely used in the pharmaceutical industry, including the monoterpene indole alkaloids (MIAs) vinblastine and vincristine, which both display anticancer activity. Both compounds can be obtained through the chemical condensation of their precursors vindoline and catharanthine extracted from leaves of the Madagascar periwinkle. However, the extensive use of these molecules in chemotherapy increases precursor demand and results in recurrent shortages, explaining why the development of alternative production approaches, such microbial cell factories, is mandatory. In this context, the precursor-directed biosynthesis of vindoline from Tabersonine in yeast-expressing heterologous biosynthetic genes is of particular interest but has not reached high production scales to date. To circumvent production bottlenecks, the metabolic flux was channeled towards the MIA of interest by modulating the copy number of the first two genes of the vindoline biosynthetic pathway, namely Tabersonine 16-hydroxylase and tabersonine-16-O-methyltransferase. Increasing gene copies resulted in an optimized methoxylation of Tabersonine and overcame the competition for Tabersonine access with the third enzyme of the pathway, Tabersonine 3-oxygenase, which exhibits a high substrate promiscuity. Through this approach, we successfully created a yeast strain that produces the fourth biosynthetic intermediate of vindoline without accumulation of other intermediates or undesired side-products. This optimization will probably pave the way towards the future development of yeast cell factories to produce vindoline at an industrial scale.
Tabersonine Inhibits the Lipopolysaccharide-Induced Neuroinflammatory Response in BV2 Microglia Cells via the NF- κ B Signaling Pathway
Molecules 2022 Nov 3;27(21):7521.PMID:36364344DOI:10.3390/molecules27217521.
The occurrence and development of neurodegenerative diseases is related to a variety of physiological and pathological changes. Neuroinflammation is one of the major factors that induces and aggravates neurodegenerative diseases. The most important manifestation of neuroinflammation is the activation of microglia. Therefore, inhibiting the abnormal activation of microglia is an important way to alleviate the occurrence of neuroinflammatory diseases. In this research, the inhibitory effect of Tabersonine (Tab) on neuroinflammation was evaluated by establishing the BV2 neuroinflammation model induced by lipopolysaccharide (LPS). It was found that Tab significantly inhibited the production and expression of nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS) in BV-2 cells stimulated by LPS. In addition, Tab can also inhibit the activation of nuclear factor-κB (NF-κB) induced by LPS, thus regulating inflammatory mediators such as inducible nitric oxide synthase (iNOS). These results indicated that Tab regulated the release of inflammatory mediators such as NO, IL-1β, TNF-α, and IL-6 by inhibiting NF-κB signaling pathway, and exerting its anti-neuroinflammatory effect. This is the first report regarding the inhibition on LPS-induced neuroinflammation in BV2 microglia cells of Tab, which indicated the drug development potential of Tab for the treatment of neurodegenerative diseases.