Negletein
(Synonyms: 黄芩素-7-甲醚; 5,6-Dihydroxy-7-methoxyflavone) 目录号 : GC39070
Negletein 是一种神经保护剂，可增强神经生长因子的作用并诱导 PC12 细胞中的神经突向外生长。Negletein 通过抑制 TNF-α 和 IL-1β 表现出有希望的抗炎活性，其 IC50 值分别为 16.4 和 10.8 μM。
Cas No.:29550-13-8
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
Negletein is a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. Negletein shows promising anti-inflammatory activity via inhibition of TNF-α and IL-1β with IC50 values of 16.4 and 10.8 μM, respectively[1].
[1]. Phan CW, et al. Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. Biofactors. 2016 Nov 12;42(6):591-599. [2]. Singh B, et al. Anti-inflammatory and immunomodulatory flavones from Actinocarya tibetica Benth.Nat Prod Res. 2013;27(23):2227-30.
| Cas No. | 29550-13-8 | SDF | |
| 别名 | 黄芩素-7-甲醚; 5,6-Dihydroxy-7-methoxyflavone | ||
| Canonical SMILES | O=C1C=C(C2=CC=CC=C2)OC3=CC(OC)=C(O)C(O)=C13 | ||
| 分子式 | C16H12O5 | 分子量 | 284.26 |
| 溶解度 | DMSO : 100 mg/mL (351.79 mM; Need ultrasonic) | 储存条件 | Store at -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 | 3.5179 mL | 17.5895 mL | 35.1791 mL |
| 5 mM | 0.7036 mL | 3.5179 mL | 7.0358 mL |
| 10 mM | 0.3518 mL | 1.759 mL | 3.5179 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 |
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| % 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。
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Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells
Biofactors 2016 Nov 12;42(6):591-599.PMID:27193378DOI:10.1002/biof.1296.
Negletein has been shown to have therapeutic potential for inflammation-associated diseases, but its effect on neurite outgrowth is still unknown. The present study showed that Negletein alone did not trigger PC12 cells to differentiate and extend neurites. When compared with the cells in the untreated control, a significant (P < 0.05) induction and a higher neurite outgrowth activity was observed when the cells were cotreated with Negletein (10 µM) and a low dose of nerve growth factor (NGF; 5 ng/mL). The neurite outgrowth process was blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was NGF-dependent. Negletein (10 µM) together with NGF (5 ng/mL) enhanced the phosphorylation of extracellular signal-regulated kinases (ERKs), protein kinase B (Akt), and cAMP response element-binding protein (CREB). The growth associated protein-43 (GAP-43) and the NGF level were also upregulated by Negletein (10 µM) and a low dose of NGF (5 ng/mL). Negletein at nanomolar concentration also was found to be sufficient to mediate the survival of serum-deprived PC12 cells up to 72 h. Taken together, Negletein might be useful as an efficient bioactive compound to protect neurons from cell death and promote neuritogenesis. © 2016 BioFactors, 42(6):591-599, 2016.
Discovery of novel Negletein derivatives as potent anticancer agents for acute myeloid leukemia
Chem Biol Drug Des 2018 Apr;91(4):924-932.PMID:29240303DOI:10.1111/cbdd.13159.
Baicalin and its aglycone baicalein derived from Scutellaria baicalensis exhibited potent anticancer effects in various types of cancer cell lines. However, the unfavorable pharmaceutical properties became the main obstacle for their potential clinical development. With the aim of development of novel anticancer agents based on the skeleton of baicalin, a series of novel Negletein derivatives were designed and synthesized. Among them, compound 8 (FZU-02,006) with an N,N-dimethylamino ethoxyl moiety at the C-6 position exhibited significant enhanced antiproliferative effect against HL-60 cells in vitro through regulating multisignaling pathways. These results revealed that compound 8 with the improved aqueous solubility (as HCl salt, >1 mg/ml) and enhanced antileukemia potency might serve as a promising lead for further development.
Crystal structures of the flavonoid Oroxylin A and the regioisomers Negletein and Wogonin
Acta Crystallogr C Struct Chem 2020 May 1;76(Pt 5):490-499.PMID:32367831DOI:10.1107/S2053229620005550.
The flavonoid Oroxylin A (6-methoxychrysin or 5,7-dihydroxy-6-methoxy-2-phenyl-4H-chromen-4-one, C16H12O5) and its regioisomers are of increasing interest for a variety of bioactive functions and their pharmaceutical formulation is of importance. Previous difficulties in the separation and misidentification of Oroxylin A from its regioisomers Wogonin (8-methoxychrysin or 5,7-dihydroxy-8-methoxy-2-phenyl-4H-chromen-4-one) and Negletein (5,6-dihydroxy-7-methoxyflavone or 5,6-dihydroxy-7-methoxy-2-phenyl-4H-chromen-4-one) render its full structural and powder X-ray characterization highly desirable. The low-temperature (100 K) crystal structures of Oroxylin A, Negletein and Wogonin sesquihydrate are reported for the first time. Wogonin crystallizes in two related but distinct hydrated forms. These have very similar powder diffractograms, indicating that such issues need to be addressed for its pharmaceutical formulation.
Multiple mechanisms of iron-induced amyloid beta-peptide accumulation in SHSY5Y cells: protective action of Negletein
Neuromolecular Med 2014 Dec;16(4):787-98.PMID:25249289DOI:10.1007/s12017-014-8328-4.
The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone Negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, Negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of Negletein, which should be explored in suitable animal models of AD.
Modulation of the Nrf2 signalling pathway in Hct116 colon carcinoma cells by baicalein and its methylated derivative Negletein
Pharm Biol 2016 Sep;54(9):1491-502.PMID:27143122DOI:10.3109/13880209.2015.1104703.
Context: Baicalein is a major compound in extracts derived from Scutellaria baicalensis Georgi (Lamiaceae) which are used in the Traditional Chinese Medicine for the treatment of inflammatory and gastrointestinal diseases. This flavonoid is an activator of the Nrf2 signalling pathway but the molecular mechanism is not clearly established. Objective: We investigated the molecular mode of baicalein-mediated Nrf2-activation in Hct116 cells by the analysis of proteasomal activity, radical-scavenging activity and the comparison with baicalein derivatives. Materials and methods: The radical-scavenging activity (TEAC, DCF) up to 25 μM, cytotoxicity (MTT assay, 48 h) up to 100 μM, proteasomal activity and the Nrf2-activation (luciferase assay, ubiquitinylation, western blot, Ser40-phosphorylation; incubation for 1 or 4 h) by concentrations up to 40 or 50 μM of the compounds were analysed in Hct116 human colon carcinoma cells. Results: No change in the ubiquitinylation of Nrf2, proteasomal activity and transcription of the NRF2 gene were detectable. Baicalein decreased the phosphorylation of Nrf2 (IC50-value approximately 20 μM) suggesting an inhibitory effect of the flavonoid on protein kinases. Since the activation of the Nrf2 pathway by baicalein might be also due to redox-activity of the compound, we investigated the effects of methylated baicalein derivatives oroxylin A, negeletein and baicaleintrimethylether. Oroxylin A and Negletein showed a comparable redox-active potential, but only Negletein (50 μM, 4 h) was able to activate Nrf2. Conclusion: This result confirms the hypothesis that baicalein, a component of extracts derived from Baical Skullcap, causes an activation of Nrf2 independent of a modulation of the cellular redox potential.