Cyclovirobuxine D
(Synonyms: 黄杨碱) 目录号 : GC38419
An alkaloid with diverse biological activities
Cas No.:860-79-7
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
Cyclovirobuxine D (CVB-D) is an alkaloid, and the main active component of the traditional Chinese medicine B. microphylla, that has diverse biological activities.1,2,3,4,5,6 It is an ether-a-go-go related gene (ERG) potassium channel blocker with an IC50 value of 19.7 μM using whole-cell patch-clamp electrophysiology in HEK293 cells expressing the human receptor.1 IERG blockade is activation-dependent, indicating CVB-D binds to open ERG channels. CVB-D increases the amount and rate of calcium release from intracellular stores in healthy neonatal rat cardiac myocytes and those isolated from adult rats with heart failure in a concentration-dependent manner.2 It also increases expression of ryanodine receptor 2 (Ryr2) and sarcoplasmic reticulum calcium ATPase 2a (Serca2a) and decreases expression of the sodium-calcium exchanger (Ncx). In vivo, CVB-D (0.5-2.0 mg/kg) reduces mortality and improves cardiac function in a rat model of congestive heart failure.3 CVB-D pretreatment (1 mg/kg per day for 4 days) inhibits myocardial apoptosis and mitochondrial cytochrome C release induced by doxorubicin in mice.4 CVB-D also induces cellular autophagy and inhibits growth of MCF-7 breast cancer cells and induces mitochondrial apoptosis in MGC803 and MKN26 gastric cancer cells.5,6
1.Zhao, J., Wang, Q., Xu, J., et al.Cyclovirobuxine D inhibits the currents of HERG potassium channels stably expressed in HEK293 cellsEur. J. Pharmacol.660(2-3)259-267(2011) 2.Yu, B., Ruan, M., Zhou, L., et al.Influence of cyclovirobuxine D on intracellular [Ca2+] regulation and the expression of the calcium cycling proteins in rat myocytesFitoterapia83(8)1653-1665(2012) 3.Yu, B., Fang, T.-H., Lü, G.-H., et al.Beneficial effect of cyclovirobuxine D on heart failure rats following myocardial infarctionFitoterapia82(6)868-877(2011) 4.Guo, Q., Guo, J., Yang, R., et al.Cyclovirobuxine D attenuates doxorubicin-induced cardiomyopathy by suppression of oxidative damage and mitochondrial biogenesis impairmentOxid. Med. Cell. Longev.2015(151972)(2015) 5.Lu, J., Sun, D., Gao, S., et al.Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cellsJ. Pharmacol. Sci.125(1)74-82(2014) 6.Wu, J., Tan, Z., Chen, J., et al.Cyclovirobuxine D inhibits cell proliferation and induces mitochondria-mediated apoptosis in human gastric cancer cellsMolecules20(11)20659-20668(2015)
| Cas No. | 860-79-7 | SDF | |
| 别名 | 黄杨碱 | ||
| Canonical SMILES | C[C@H](NC)[C@@]1([H])[C@H](O)C[C@@]2(C)[C@]3([H])CC[C@@]4([H])C(C)(C)[C@@H](NC)CC[C@]4(C5)[C@]35CC[C@@]21C | ||
| 分子式 | C26H46N2O | 分子量 | 402.66 |
| 溶解度 | Ethanol: 13 mg/mL (32.29 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 | 2.4835 mL | 12.4174 mL | 24.8348 mL |
| 5 mM | 0.4967 mL | 2.4835 mL | 4.967 mL |
| 10 mM | 0.2483 mL | 1.2417 mL | 2.4835 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。
Cyclovirobuxine D, a cardiovascular drug from traditional Chinese medicine, alleviates inflammatory and neuropathic pain mainly via inhibition of voltage-gated Cav3.2 channels
Front Pharmacol 2022 Dec 21;13:1081697.PMID:36618940DOI:10.3389/fphar.2022.1081697.
Cyclovirobuxine D (CVB-D), the main active constituent of traditional Chinese medicine Buxus microphylla, was developed as a safe and effective cardiovascular drug in China. B. microphylla has also been used to relieve various pain symptoms for centuries. In this study, we examined and uncovered strong and persistent analgesic effects of Cyclovirobuxine D against several mouse models of pain, including carrageenan- and CFA-induced inflammatory pain and paclitaxel-mediated neuropathic hypersensitivity. Cyclovirobuxine D shows comparable analgesic effects by intraplantar or intraperitoneal administration. Cyclovirobuxine D potently inhibits voltage-gated Cav2.2 and Cav3.2 channels but has negligible effects on a diverse group of nociceptive ion channels distributed in primary afferent neurons, including Nav1.7, Nav1.8, TRPV1, TPRA1, TRPM8, ASIC3, P2X2 and P2X4. Moreover, inhibition of Cav3.2, rather than Cav2.2, plays a dominant role in attenuating the excitability of isolated dorsal root ganglion neurons and pain relieving effects of Cyclovirobuxine D. Our work reveals that a currently in-use cardiovascular drug has strong analgesic effects mainly via blockade of Cav3.2 and provides a compelling rationale and foundation for conducting clinical studies to repurpose Cyclovirobuxine D in pain management.
Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway
Int J Oncol 2020 Jul;57(1):183-196.PMID:32319595DOI:10.3892/ijo.2020.5038.
Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.
Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells
Int J Mol Sci 2021 May 29;22(11):5820.PMID:34072333DOI:10.3390/ijms22115820.
Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that Cyclovirobuxine D (CVB-D), a natural compound derived from Buxus microphylla, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patients.
Cyclovirobuxine D Ameliorates Experimental Diabetic Cardiomyopathy by Inhibiting Cardiomyocyte Pyroptosis via NLRP3 in vivo and in vitro
Front Pharmacol 2022 Jul 5;13:906548.PMID:35865939DOI:10.3389/fphar.2022.906548.
Diabetic cardiomyopathy (DCM) is one of the common complications of diabetic patients, which can induce myocardial hypertrophy, cardiac fibrosis, and heart failure. Growing evidence has shown that the occurrence and development of DCM are accompanied by pyroptosis which is an NLRP3-mediated intense inflammatory cell death. Cyclovirobuxine D (CVB-D) has been shown to significantly ameliorate DCM and anti-inflammatory effects associated with cardiomyopathy, but it is unclear whether it has an effect on cardiomyocyte pyroptosis accompanying DCM. Therefore, the purpose of the present study was to explore the ameliorating effect of CVB-D on cardiomyocyte pyroptosis associated with DCM and its molecular regulation mechanism. Type 2 diabetes in C57BL/6 mice was reproduced by the high-fat and high-glucose diet (HFD) combined with low-dose streptozotocin (STZ). The characteristics of DCM were evaluated by cardiac ultrasonography, serum detection, and histopathological staining. The results suggested that CVB-D could significantly alleviate the cardiac pathology of DCM. Then, we explored the mechanism of CVB-D on primary neonatal rat cardiomyocyte (PNRCM) injury with high glucose (HG) in vitro to simulate the physiological environment of DCM. Preincubation with CVB-D could significantly increase cell viability, attenuate cytopathological changes and inhibit the expression levels of pyroptosis-related proteins. Further research found that the myocardial improvement effect of CVB-D was related to its inhibition of NLRP3 expression. In conclusion, our data suggest that CVB-D can ameliorate DCM by inhibiting cardiomyocyte pyroptosis via NLRP3, providing a novel molecular target for CVB-D clinical application.
Cyclovirobuxine D Brain-Targeted Liposomes Improve Cerebral Ischemia-Reperfusion Injury via Anti-Oxidant Stress and Activating Autophagy
J Biomed Nanotechnol 2022 Apr 1;18(4):1146-1157.PMID:35854463DOI:10.1166/jbn.2022.3327.
One of the main issues faced by nervous system diseases is that drugs are difficult to enter the brain. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study concentrated on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. Middle cerebral artery occlusion-reperfusion induced CIRI model rats to explore the protective effect of CVBD brain-targeted liposome on CIRI. Moreover, the protective effect of CVBD liposomes on OGD/R-injured HT22 cells was examined by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions were analyzed by Western blot. The classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulatedmechanism of CVBD brain-targeted liposomes in treating CIRI. CVBD liposomes increased cell viability and decreased ROS level, improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated with anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro.