Stepharine
(Synonyms: (+)-千金藤碱) 目录号 : GC64456
Stepharine 是天然的生物碱，可直接靶向 TLR4 (TLR4 抑制剂)，结合 TLR4/MD2 复合体。Stepharine 具有抗衰老、抗病毒和抗高血压等活性。
Cas No.:2810-21-1
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
Stepharine, an natural alkaloid, directly interactes with TLR4 and binds to the TLR4/MD2 complex (TLR4 inhibitor). Stepharine possesses anti-aging, anti-viral and anti-hypertensive effects[1].
Stepharine (10, 30 μM) substantially inhibits nitric oxide (NO) release as well as the mRNA and protein expression of pro-inflammatory mediators [inducible nitric oxide synthase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β] in LPS-activated BV-2 cells[1].Stepharine (10, 30 μM) inhibits LPS-induced increase of TLR4 expression, IκBα phosphorylation, and NF-κB p65 nuclear translocation[1].Stepharine exhibits neuroprotective effects on SH-SY5Y cells cultured with LPS-treated conditioned medium. Stepharine has also shown to inhibit cholinesterase in vitro[1].
Stepharine (500 μg/kg) inhibited NeuN+ cells loss and Iba-1+ cells increase in the MCAO ischemic cortex[1].
[1]. Tingyu Hao, et al. Inflammatory mechanism of cerebral ischemia-reperfusion injury with treatment of stepharine in rats. Phytomedicine. 2020 Dec;79:153353.
| Cas No. | 2810-21-1 | SDF | Download SDF |
| 别名 | (+)-千金藤碱 | ||
| 分子式 | C18H19NO3 | 分子量 | 297.35 |
| 溶解度 | DMSO : 25 mg/mL (84.08 mM; Need ultrasonic) | 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 | 3.363 mL | 16.8152 mL | 33.6304 mL |
| 5 mM | 0.6726 mL | 3.363 mL | 6.7261 mL |
| 10 mM | 0.3363 mL | 1.6815 mL | 3.363 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。
Tempo-Spatial Pattern of Stepharine Accumulation in Stephania Glabra Morphogenic Tissues
Int J Mol Sci 2019 Feb 13;20(4):808.PMID:30781887DOI:10.3390/ijms20040808.
Alkaloids attract great attention due to their valuable therapeutic properties. Stepharine, an aporphine alkaloid of Stephania glabra plants, exhibits anti-aging, anti-hypertensive, and anti-viral effects. The distribution of aporphine alkaloids in cell cultures, as well as whole plants is unknown, which hampers the development of bioengineering strategies toward enhancing their production. The spatial distribution of Stepharine in cell culture models, plantlets, and mature micropropagated plants was investigated at the cellular and organ levels. Stepharine biosynthesis was found to be highly spatially and temporally regulated during plant development. We proposed that self-intoxication is the most likely reason for the failure of the induction of alkaloid biosynthesis in cell cultures. During somatic embryo development, the toxic load of alkaloids inside the cells increased. Only specialized cell sites such as vascular tissues with companion cells (VT cells), laticifers, and parenchymal cells with inclusions (PI cells) can tolerate the accumulation of alkaloids, and thus circumvent this restriction. S. glabra plants have adapted to toxic pressure by forming an additional transport secretory (laticifer) system and depository PI cells. Postembryonic growth restricts specialized cell site formation during organ development. Future bioengineering strategies should include cultures enriched in the specific cells identified in this study.
Inflammatory mechanism of cerebral ischemia-reperfusion injury with treatment of Stepharine in rats
Phytomedicine 2020 Dec;79:153353.PMID:33007731DOI:10.1016/j.phymed.2020.153353.
Background: Increasing evidence has shown that microglia-induced neuroinflammation is involved in the pathogenesis of ischemic stroke. Stepharine, one of the alkaloids extracted from Stephania japonica (Thunb.) Miers, exhibited strong inhibitory effect on microglial overactivation. However, it is not known whether it has the potential to prevent ischemic stroke. Methods: The neuroprotective and anti-neuroinflammatory effects of Stepharine were investigated in vivo and in vitro, using a rat model of middle cerebral artery occlusion (MCAO) and lipopolysaccharide (LPS)-stimulated BV-2 cells, respectively. Results: In vivo, Stepharine (500 μg/kg) suppressed neurological deficits scores, brain water content and cerebral infarct volume induced by MCAO. Moreover, Stepharine (500 μg/kg) inhibited NeuN+ cells loss and Iba-1+ cells increase in the MCAO ischemic cortex. In vitro, Stepharine (10, 30 μM) substantially inhibited nitric oxide release as well as the mRNA and protein expression of pro-inflammatory mediators [inducible nitric oxide synthase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β] in LPS-activated BV-2 cells. LPS-induced increase of TLR4 expression, IκBα phosphorylation, and NF-κB p65 nuclear translocation was inhibited by Stepharine (10, 30 μM). Molecular docking analysis showed that Stepharine directly interacted with TLR4. SPR assay further confirmed that Stepharine could bind to the TLR4/MD2 complex. Meanwhile, Stepharine exhibited neuroprotective effects on SH-SY5Y cells cultured with LPS-treated conditioned medium. Conclusion: Our study demonstrated for the first time that Stepharine improved the outcomes in MCAO rats, reduced neuronal loss, and suppressed microglial overactivation via the inhibition of TLR4/NF-κB pathway. These results suggest that Stepharine might be a potential therapeutic agent for the treatment of ischemic stroke.
Isoquinoline alkaloids from Asimina triloba
Nat Prod Res 2019 Oct;33(19):2823-2829.PMID:30453785DOI:10.1080/14786419.2018.1504045.
A new aporphine glycoside, (-)-anolobine-9-O-β-D-glucopyranoside was isolated from the twigs of pawpaw (Asimina triloba) along with 7 known alkaloids including five aporphine alkaloids (anolobine, nornuciferine, norushinsunine, liriodenine, and lysicamine), a proaporhine alkaloid (Stepharine), and a tetrahydrobenzylisoquinoline alkaloid (coclaurine). Among these compounds, nornuciferine, lysicamine, Stepharine, and coclaurine are reported for the first time from this plant. The structure of the new compound was elucidated by spectroscopic methods, including 1 D, 2 D NMR, and HRESI-MS. The absolute configuration of compounds 1, 2, 7 and 8 was determined by CD experiment.
Development of mass spectrometry selected reaction monitoring method for quantitation and pharmacokinetic study of Stepharine in rabbit plasma
Adv Pharmacol Sci 2014;2014:961850.PMID:24696679DOI:10.1155/2014/961850.
Highly sensitive liquid chromatography mass spectrometry method on triple quadrupole (QQQ) mass spectrometer was successfully applied for pharmacokinetic study of Stepharine in rabbit plasma. Specific ion transitions of Stepharine protonated precursor ion were selected and recorded in the certain retention time employing dynamic selected reaction monitoring mode. The developed method facilitated quantitative measurements of Stepharine in plasma samples in linear range of five orders of magnitude with high accuracy and low standard deviation coefficient and pharmacokinetics parameters were calculated. The apparent volume of Stepharine distribution (estimated as ratio of clearance to elimination rate constant, data not shown) allows us to assume that Stepharine was extensively distributed throughout the body.
Alkaloids of Abuta panurensis Eichler: In silico and in vitro study of acetylcholinesterase inhibition, cytotoxic and immunomodulatory activities
PLoS One 2020 Sep 29;15(9):e0239364.PMID:32991579DOI:10.1371/journal.pone.0239364.
Natural products obtained from species of the genus Abuta (Menispermaceae) are known as ethnobotanicals that are attracting increasing attention due to a wide range of their pharmacological properties. In this study, the alkaloids Stepharine and 5-N-methylmaytenine were first isolated from branches of Abuta panurensis Eichler, an endemic species from the Amazonian rainforest. Structure of the compounds was elucidated by a combination of 1D and 2D NMR spectroscopic and MS and HRMS spectrometric techniques. Interaction of the above-mentioned alkaloids with acetylcholinesterase enzyme and interleukins IL-6 and IL-8 was investigated in silico by molecular docking. The molecules under investigation were able to bind effectively with the active sites of the AChE enzyme, IL-6, and IL-8 showing affinity towards the proteins. Along with the theoretical study, acetylcholinesterase enzyme inhibition, cytotoxic, and immunomodulatory activity of the compounds were assessed by in vitro assays. The data obtained in silico corroborate the results of AChE enzyme inhibition, the IC50 values of 61.24μM for Stepharine and 19.55μM for 5-N-methylmaytenine were found. The compounds showed cytotoxic activity against two tumor cell lines (K562 and U937) with IC50 values ranging from 11.77 μM to 28.48 μM. The in vitro assays revealed that both alkaloids were non-toxic to Vero and human PBMC cells. As for the immunomodulatory activity, both compounds inhibited the production of IL-6 at similar levels. Stepharine inhibited considerably the production of IL-8 in comparison to 5-N-methylmaytenine, which showed a dose dependent action (inhibitory at the IC50 dose, and stimulatory at the twofold IC50 one). Such a behavior may possibly be explained by different binding modes of the alkaloids to the interleukin structural fragments. Occurrence of the polyamine alkaloid 5-N-methylmaytenine was reported for the first time for the Menispermaceae family, as well as the presence of Stepharine in A. panurensis.