Crebanine
(Synonyms: 克班宁) 目录号 : GC35747
An aporphine alkaloid with diverse biological activities
Cas No.:25127-29-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
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Crebanine is an aporphine alkaloid that has been found in Stephania venosa and has diverse biological activities.1,2,3,4,5 It is an antagonist of α7 nicotinic acetylcholine receptors (nAChRs; IC50 = 19.1 ?M) and inhibits sodium currents (INa) in isolated guinea pig ventricular myocytes (IC50 = 283 ?M).1,2 Crebanine is active against the Gram-positive bacteria M. lysodeikticus, B. cereus, B. megaterium, B. subtilis, and S. aureus (MICs = 0.312, 0.213, 0.312, 0.312, and 0.312 g/L, respectively), as well as the plant pathogenic fungi C. kaki, G. haraeanum, P. oryzae, R. solani, and C. graminicola (EC50s = 111, 64.7, 18.9, 42.5, and 40.5 mg/L, respectively).3 It inhibits the LPS-induced production of TNF-α, IL-6, nitric oxide (NO), and prostaglandin E2 in RAW 264.7 macrophages when used at a concentration of 29.5 ?M.4 Crebanine inhibits the proliferation of A549 lung, MDA-MB-231 and MCF-7 breast, and SKOV3 and Caov-3 ovarian cells and reduces TNF-α induced invasion and migration of A549 cells in a concentration-dependent manner.5 It prevents scopolamine-induced memory deficits in the Morris water maze in mice when administered at a dose of 25 mg/kg.1
1.Rojsanga, P., Boonyarat, C., Utsintong, M., et al.The effect of crebanine on memory and cognition impairment via the alpha-7 nicotinic acetylcholine receptorLife Sci.91(3-4)107-114(2012) 2.Xiao-Shan, H., Qing, L., Yun-Shu, M., et al.Crebanine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytesChin. J. Nat. Med.12(1)20-23(2014) 3.Deng, Y., Yu, Y., Luo, H., et al.Antimicrobial activity of extract and two alkaloids from traditional Chinese medicinal plant Stephania dielsianaFood Chem.124(4)1556-1560(2011) 4.Intayoung, P., Limtrakul, P., and Yodkeeree, S.Antiinflammatory activities of crebanine by inhibition of NF-κB and AP-1 activation through suppressing MAPKs and Akt signaling in LPS-induced RAW264.7 macrophagesBiol. Pharm. Bull.39(1)54-61(2016) 5.Yodkeeree, S., Pompimon, W., and Limtrakul, P.Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene productsTumour Biol.35(9)8615-8624(2014)
| Cas No. | 25127-29-1 | SDF | |
| 别名 | 克班宁 | ||
| Canonical SMILES | CN1CCC(C2=C3C4=CC=C(OC)C(OC)=C4C[C@@]12[H])=CC5=C3OCO5 | ||
| 分子式 | C20H21NO4 | 分子量 | 339.39 |
| 溶解度 | Soluble in DMSO | 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 | 2.9465 mL | 14.7323 mL | 29.4646 mL |
| 5 mM | 0.5893 mL | 2.9465 mL | 5.8929 mL |
| 10 mM | 0.2946 mL | 1.4732 mL | 2.9465 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 | ||||||||||
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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。
Crebanine induces ROS-dependent apoptosis in human hepatocellular carcinoma cells via the AKT/FoxO3a signaling pathway
Front Pharmacol 2023 Feb 16;14:1069093.PMID:36874025DOI:10.3389/fphar.2023.1069093.
Background: Hepatocellular carcinoma (HCC), as an aggressive cancer with a high mortality rate, needs high-efficiency and low-toxicity drug therapy. Natural products have great potential as candidate lead compounds for the development of new HCC drugs. Crebanine is an isoquinoline alkaloid derived from Stephania with various potential pharmacological effects such as anti-cancer. However, the molecular mechanism underlying crebanine-induced liver cancer cells apoptosis has not been reported. Here, we investigated the effect of Crebanine on HCC and identified a potential mechanism of action. Methods: In this paper, we intend to detect the toxic effects of Crebanine on hepatocellular carcinoma HepG2 cells through a series of in vitro experiments, including detecting the effects of Crebanine on the proliferation of HepG2 cells using the CCK8 method and plate cloning assay, observing the growth status and morphological changes of Crebanine on HepG2 cells by inverted microscopy; and using the Transwell method to determine the the effect of Crebanine on the migration and invasion ability of HepG2 cells; using Hoechst 33258 assay to stain cancer cells, thus observing the effect of Crebanine on the morphology of HepG2 apoptotic cells, and detecting the apoptotic state and level of HepG2 cells by flow cytometry; using ROS kit and JC-1 assay kit to detect the changes of reactive oxygen species and mitochondrial membrane potential of HepG2 The immunofluorescence assay was taken to verify whether Crebanine had an effect on the expression of p-FoxO3a in cancer cells; the Wetern blot assay was also used to examine the effect of Crebanine on proteins related to the mitochondrial apoptotic pathway and its effect on the regulation of the relative protein expression of AKT/FoxO3a axis; after this, NAC and AKT inhibitor LY294002 were used to cells were pretreated with NAC and AKT inhibitor LY294002, respectively, in order to further validate the inhibitory effect of Crebanine. Results: It was shown that Crebanine effectively inhibited the growth and capacity of HepG2 cells migration and invasion in a dose-dependent manner. Furthermore, the effect of Crebanine on the morphology of HepG2 cells was observed through microscopy. Meanwhile, Crebanine induced apoptosis by causing reactive oxygen species (ROS) burst and mitochondrial membrane potential (MMP) disrupt. We found that Crebanine could down-regulate Bcl-2 and up-regulate Bax, cleaved-PARP, cleaved-caspase-3 and cleaved-caspase-9, but these effects were overturned by ROS inhibitor N-acetylcysteine (NAC). Crebanine also down-regulated p-AKT and p-FoxO3a, and the PI3K inhibitor LY294002 significantly enhances this effect. We also found that the expression of AKT/FoxO3a signaling pathway was ROS-dependent. As shown by Western blots, NAC could partially attenuate the inhibitory effect of Crebanine on AKT and FoxO3a phosphorylation. Conclusion: Based on our results, our results suggest that Crebanine, as a compound with potential anticancer activity, has significant cytotoxic effects on hepatocellular carcinoma,and it likely induces apoptosis via ROS in the mitochondrial pathway and simultaneously affects the biological function of HCC via the ROS-AKT-FoxO3a signaling axis.
Crebanine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes
Chin J Nat Med 2014 Jan;12(1):20-3.PMID:24484592DOI:10.1016/S1875-5364(14)60004-2.
Aim: To study the effects of Crebanine on voltage-gated Na(+) channels in cardiac tissues. Methods: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using the whole cell voltage-clamp technique. Results: Crebanine reversibly inhibited Na(+) current with an IC50 value of 0.283 mmol·L(-1) (95% confidence range: 0.248-0.318 mmol·L(-1)). Crebanine at 0.262 mmol·L(-1) caused a negative shift (about 12 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve. Conclusion: In addition to blocking other voltage-gated ion channels, Crebanine blocked Na(+) channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na(+) channels in cardiac tissues.
Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
Tumour Biol 2014 Sep;35(9):8615-24.PMID:24867094DOI:10.1007/s13277-014-1998-6.
Crebanine is an alkaloid known to exhibit anticancer, but its mechanism is not well understood. Besides, the nuclear factor-kappa B (NF-κB) transcription factor has been correlated with inflammation, carcinogenesis, tumor cell survival, invasion, and angiogenesis. In this study, we investigated the effects of Crebanine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation and the expression of NF-κB-regulated gene products. We found that Crebanine reduced the cell proliferation of lung, ovarian, and breast cancer cells. Crebanine also potentiated TNF-α-induced apoptosis which correlated with the suppression of the gene products linked to cell survival, B cell lymphoma-extra large, and proliferation, cyclin D1. In addition, Crebanine affected TNF-α-induced activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase cleavage, indicating that the apoptotic effects of TNF-α were enhanced by Crebanine. Moreover, Crebanine reduced TNF-α-induced A549 cell invasion and migration. Furthermore, Crebanine suppressed the TNF-α-mediated expression of proteins that involved cancer cell invasion (matrix metalloproteinase 9 urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and intercellular adhesion molecule 1) and angiogenesis (COX-2 and VEGF), all of which are known to be regulated by NF-κB. We also demonstrated that TNF-α induced NF-κB DNA-binding activity, which was inhibited by Crebanine. Moreover, Crebanine suppressed the TNF-α-induced degradation of inhibitor of NF-κB alpha (IκBa), which led to reduced NF-κB translocation to the nucleus. Taken together, our results demonstrated that Crebanine reduced TNF-α-induced cancer cell proliferation, invasion, and survival by suppressing NF-κB activity and expression profile of its downstream genes.
Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages
Biol Pharm Bull 2016;39(1):54-61.PMID:26499331DOI:10.1248/bpb.b15-00479.
Crebanine, an aporphine alkaloid, displays various biological activities such as anticancer and antimicrobial activities. In this study, we further investigated the suppressive effect of Crebanine on lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and the molecular mechanisms underlying these activities in RAW264.7 macrophages. Crebanine inhibited the production of proinflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha in LPS-induced RAW264.7 cells. Moreover, Crebanine suppressed LPS-induced inducible nitric oxide (iNO) and prostaglandin E2 and reduced the expression of iNO synthase and cyclooxygenase-2 in RAW264.7 cells. Crebanine suppressed LPS-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling. In addition, the specific inhibitor of MAPKs and Akt reduced the expression of IL-6 and NO production in LPS-induced macrophages. Furthermore, Crebanine inhibited LPS-induced nuclear factor kappa B (NF-κB) activation by reducing the phosphorylation of p65 at Ser536 but not the p65 translocation to the nucleus and inhibitory factor kappa B alpha degradation. Crebanine also suppressed phosphorylation and nucleus translocation of activator protein-1 (AP-1). These observations suggest that the antiinflammatory properties of Crebanine may stem from the inhibition of proinflammatory mediators via suppression of the NF-κB, AP-1, MAPKs, and Akt signaling pathways.
The effect of Crebanine on memory and cognition impairment via the alpha-7 nicotinic acetylcholine receptor
Life Sci 2012 Aug 21;91(3-4):107-14.PMID:22749860DOI:10.1016/j.lfs.2012.06.017.
Aims: The aims of the present study were to investigate the effect of Crebanine on memory and cognition impairment in mice and to elucidate the underlying molecular mechanisms. Main methods: The memory-enhancing effects of Crebanine were assessed with a water maze test using scopolamine-induced amnesic mice. The molecular mechanism was explored in silico by docking Crebanine against acetylcholine binding proteins (AChBPs) and in vitro with a radioligand competition assay using (±)-[(3)H]-epibatidine. The pharmacological behavior was assessed by observing changes to the functional activity of α7-nAChRs expressed in Xenopus oocytes and by fluorescent assays on recombinant ligand gated ion channel (LGIC) receptors expressed in mammalian cells. Key findings: The administration of Crebanine significantly improved the cognitive deficits induced by scopolamine, as measured by the water maze test. The docking results demonstrated that Crebanine bound to the active binding site of the AChBP template with a good docking energy. Crebanine significantly inhibited the binding of (±)-[(3)H]-epibatidine to AChBPs with K(i) values of 179 nM and 538 nM for Ls and Ac, respectively. Further functional assays performed using two separate protocols indicated that Crebanine is an antagonist of the α7-nAChR with an IC(50) of 19.1μM. Significance: The observed actions of Crebanine against amnesia and its effect on α7-nAChRs will be beneficial for target-based drug design; Crebanine or its scaffold can be used as the starting point to develop a drug for Alzheimer's disease. The cognition-enhancing effects of Crebanine and the underlying mechanism based on α7-nAChRs are consistent with its traditional use. These findings demonstrate the potential utility of Crebanine in the development of neurodegenerative therapy.