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Purity: ≥98%
Cyclovirobuxine D (also known as CVB-D or Bebuxine) is a naturally occurring and bioactive substance that was isolated from the Buxus microphylla and has been used to treat acute myocardial ischemia. The human breast cancer cell line MCF-7 may be induced to undergo autophagy by the alkaloid cyclovirobuxine D, which is found in a traditional Chinese herb. In rats with experimental myocardial injury brought on by sympathetic overactivity, it has a preventing effect against oxidative stress and energy metabolism. Additionally, Cyclovirobuxine D helps treat heart failure brought on by myocardial infarction, which supports its potential as a new treatment for heart failure.
| Targets |
Natural alkaloid; autophagy; Akt; mTOR[1] Akt/mTOR signaling pathway, autophagy-related proteins (LC3, p62), apoptotic proteins (Bcl-2, Bax) [1] - Mitochondrial apoptotic pathway-related proteins (Bcl-2, Bax, caspase-3, caspase-9, PARP) (IC50: ~35 μM for SGC-7901 cells; ~42 μM for MGC-803 cells at 72 hours) [2] - Myocardial function-related targets, oxidative stress-related enzymes (SOD, MDA), myocardial apoptotic proteins (Bcl-2, Bax)[3] |
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| ln Vitro |
Only 10% of MGC-803 cells and 20% of MKN28 cells survived 72 hours after treatment with cyclobuxine D (0-240 µM; 24-72 hours) due to a concentration- and time-dependent decrease in cell viability following CVB-D therapy[2]. Gastric cancer cells' cell cycle is stopped in the S phase in a concentration-dependent manner by cyclobuxine D (0-120 µM; 48 hours) [2]. Cyclovirobuxine D (0-120 µM; 48 hours) induces concentration-dependent apoptosis in gastric cancer cells, particularly early apoptosis. In gastric cancer cells, cyclobuxine D (0-120 µM; 48 hours) induces apoptosis via upregulating cleaved Caspase-3, Bax/Bcl-2 ratio, and other apoptosis-related proteins [2].
In human breast cancer MCF-7 cells, Cyclovirobuxin D (CVB-D) (20-80 μM) induced autophagy-associated cell death in a dose-dependent manner. It inhibited Akt and mTOR phosphorylation, upregulated LC3-II/LC3-I ratio, and downregulated p62 expression. It also suppressed cell proliferation with an IC50 of ~40 μM at 72 hours, and induced mild apoptosis (12-18% apoptotic rate at 60 μM) [1] - In human gastric cancer cells (SGC-7901, MGC-803), Cyclovirobuxin D (CVB-D) (10-60 μM) inhibited proliferation in a dose- and time-dependent manner (IC50: ~35 μM for SGC-7901; ~42 μM for MGC-803 at 72 hours). It triggered mitochondria-mediated apoptosis by downregulating Bcl-2, upregulating Bax, activating caspase-3 and caspase-9, and cleaving PARP. It also reduced clone formation efficiency (inhibition rate ~55% at 40 μM for SGC-7901) [2] |
| ln Vivo |
The effect of Cyclovirobuxine D, an active ingredient from Buxus microphylla, was investigated in the potential prevention of cardiac dysfunction in rats with congestive heart failure. Heart failure was induced by left coronary artery occlusion and verified using echocardiography. Cyclovirobuxine D was administered for 30 days (0.5, 1.0 and 2.0mg/kg, ig) and mortality, cardiac function, hemodynamics, microcirculation, histology and ultrastructure assessments were observed. Results from the present study suggest that Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction and supports the potential for Cyclovirobuxine D as a new therapy for heart failure.[3]
In rats with heart failure following myocardial infarction, oral administration of Cyclovirobuxin D (CVB-D) (10 mg/kg, 20 mg/kg, 40 mg/kg, once daily for 4 weeks) improved cardiac function. It increased left ventricular ejection fraction (LVEF) by ~18%, ~25%, and ~32% respectively, reduced left ventricular end-diastolic volume (LVEDV), and alleviated myocardial fibrosis. It also inhibited myocardial cell apoptosis by upregulating Bcl-2 and downregulating Bax, and reduced oxidative stress (increased SOD activity, decreased MDA content) in myocardial tissues [3] |
| Enzyme Assay |
Akt/mTOR kinase activity assay: Recombinant Akt and mTOR kinases were incubated with ATP, specific peptide substrates, and Cyclovirobuxin D (CVB-D) (0-80 μM) at 37°C for 45 minutes. Phosphorylated substrates were detected by ELISA, and kinase inhibition rates were calculated [1]
- Caspase-3/caspase-9 activity assay: Cell lysates from CVB-D-treated gastric cancer cells were incubated with caspase-specific fluorescent substrates at 37°C for 1 hour. Fluorescence intensity was measured to quantify caspase activation [2] - SOD/MDA activity assay: Myocardial tissue homogenates from CVB-D-treated rats were prepared. SOD activity was detected by xanthine oxidase method, and MDA content was measured by thiobarbituric acid reaction method [3] |
| Cell Assay |
Cell Viability Assay[2]
Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60, 120 and 240 µM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: diminished cell viability and colony-forming ability of gastric cancer cells during cell cycle Analysis[2] Cell Types: MGC-803 and MKN28 cells Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Cell cycle progression of MGC-803 and MKN28 cells is arrested. Apoptosis analysis[2] Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis in MGC-803 and MKN28 cells. Western Blot Analysis[2] Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Up-regulation of cleaved Caspase-3 and Bax, and diminished expression of Bcl-2. Breast cancer cell assay: MCF-7 cells were seeded in 96-well plates and treated with Cyclovirobuxin D (CVB-D) (0-80 μM) for 24-72 hours. Cell viability was detected by MTT assay; autophagy was observed by immunofluorescence staining of LC3 puncta; autophagy- and pathway-related proteins (Akt, p-Akt, mTOR, p-mTOR, LC3, p62) were analyzed by Western blot; apoptosis was detected by Annexin V-FITC/PI double staining [1] - Gastric cancer cell assay: SGC-7901/MGC-803 cells were treated with Cyclovirobuxin D (CVB-D) (0-60 μM) for 48-72 hours. Cell proliferation was assessed by CCK-8 assay; clone formation assay was performed by seeding cells in 6-well plates and culturing for 14 days after CVB-D treatment; apoptosis was detected by flow cytometry; Bcl-2, Bax, caspase-3, caspase-9, and PARP expression was analyzed by Western blot [2] |
| Animal Protocol |
Effect of CVB-D on survival rate[3]
In the vehicle group, four rats died during the treatment period and the survival rate was 66.7%. The survival rate for the captopril and CVB-D (0.5, 1.0 and 2.0 mg/kg, ig) groups was 83.33%, 75.0%, 75.0% and 83.33% respectively. None of the sham-operated rats died during the experimental timeframe. The cause of death included acute heart failure, bleeding, serious arrhythmia, and respiratory failure. Myocardial infarction-induced heart failure model: Rats were subjected to left anterior descending coronary artery ligation to induce myocardial infarction. One week after surgery, rats were randomly divided into control and Cyclovirobuxin D (CVB-D) treatment groups. CVB-D was dissolved in normal saline and administered by oral gavage at 10 mg/kg, 20 mg/kg, or 40 mg/kg once daily for 4 weeks. Cardiac function (LVEF, LVEDV) was evaluated by echocardiography. Rats were sacrificed after treatment, and myocardial tissues were collected for histological (HE staining, Masson staining) and molecular biological analysis [3] |
| Toxicity/Toxicokinetics |
The oral LD50 for mice was 293 mg/kg. In vitro experiments showed that cycloverobuxin D (CVB-D) at concentrations up to 80 μM had no significant cytotoxicity to normal mammary epithelial cells (MCF-10A) and normal gastric mucosal cells (GES-1) [1][2]. In vivo experiments showed that oral administration of cycloverobuxin D (CVB-D) (up to 40 mg/kg for 4 weeks) to rats with heart failure did not cause significant changes in body weight, organ index, or serum ALT/AST/creatinine levels [3].
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| References |
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| Additional Infomation |
Cyclovirobuxine D has been reported in Buxus microphylla and Buxus sempervirens, and available data are available. Cyclovistacin D (CVB-D) is an alkaloid isolated from the leaves and stems of Buxus microphylla Sieb. et al. Zook. Rehd. et al. Wells. [1][2][3] - Its antitumor effect in breast cancer cells is achieved by inhibiting the Akt/mTOR signaling pathway to induce autophagy-related cell death. [1] - In gastric cancer cells, it exerts antitumor activity through the mitochondrial-mediated apoptosis pathway (Bcl-2/Bax-caspase-PARP). [2] - It improves cardiac function in patients with heart failure after myocardial infarction by inhibiting cardiomyocyte apoptosis, reducing oxidative stress, and alleviating myocardial fibrosis. [3]
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| Molecular Formula |
C26H46N2O
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|---|---|---|
| Molecular Weight |
402.66
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| Exact Mass |
402.361
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| Elemental Analysis |
C, 77.55; H, 11.52; N, 6.96; O, 3.97
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| CAS # |
860-79-7
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| Related CAS # |
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| PubChem CID |
260439
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
495.7±10.0 °C at 760 mmHg
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| Flash Point |
34.1±9.6 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.551
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| LogP |
4.86
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
692
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| Defined Atom Stereocenter Count |
10
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| SMILES |
C[C@@]12C[C@@H](O)[C@H]([C@H](C)NC)[C@@]1(C)CC[C@@]13C[C@]41CC[C@H](NC)C(C)(C)[C@@H]4CC[C@@H]23
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| InChi Key |
GMNAPBAUIVITMI-ABNIRSKTSA-N
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| InChi Code |
InChI=1S/C26H46N2O/c1-16(27-6)21-17(29)14-24(5)19-9-8-18-22(2,3)20(28-7)10-11-25(18)15-26(19,25)13-12-23(21,24)4/h16-21,27-29H,8-15H2,1-7H3/t16-,17+,18-,19-,20-,21-,23+,24-,25+,26-/m0/s1
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| Chemical Name |
(1S,3R,6S,8R,11S,12S,14R,15S,16R)-7,7,12,16-tetramethyl-6-(methylamino)-15-[(1S)-1-(methylamino)ethyl]pentacyclo[9.7.0.01,3.03,8.012,16]octadecan-14-ol
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.8 mg/mL clear EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.8 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 | 4.9670 mL | |
| 10 mM | 0.2483 mL | 1.2417 mL | 2.4835 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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