| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Natural; autophagy
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| ln Vitro |
Another important finding was the neuroprotective role of corynoxine B (Cory B) in Mn-induced autophagic dysregulation and neurotoxicity. We set up six experimental groups: control (culture solution); 200 μM Mn treatment; 100 μM Cory B-alone treatment; and three different pretreated concentrations of Cory B (25, 50, and 100 μM). Our results showed that Cory B ameliorated Mn-induced autophagic dysregulation and neurotoxicity partly by dissociating HMGB1 from alpha-synuclein and inhibiting mTOR signaling.[1]
Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNCA, which may be attributed to its ability to block SNCA-HMGB1 interaction. Based on these findings, we propose that SNCA-induced impairment of autophagy occurs, in part, through HMGB1, which may provide a potential therapeutic target for PD.[2] |
| ln Vivo |
Here, we report that Corynoxine B (Cory B) enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.[3]
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| Cell Assay |
SILAC labeling was done according to the instructions provided by Thermo Scientific. According to the weights of the labeled essential amino acids, N2a cells were divided into two groups: “heavy” (13C6 15N2 l-lysine-2HCl and 13C6 15N4 l-arginine-HCl) and “light” (l-lysine-2HCl, l-Arginine-HCl). Each group of N2a cells was grown over 6 generations in “light” and “heavy” SILAC media to allow full incorporation of amino acids into proteins. The “light” and “heavy” groups were transfected with Flag-Beclin 1 and then treated with DMSO or Cory B for 6 h. The cell lysates were mixed at a ratio of 1:1 and co-IP were subjected to pull-down with anti-Flag magnetic beads and analyzed by LC–MS/MS.[3]
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| Animal Protocol |
For the 2-month-old mice experiment, we selected 2-month-old heterozygous mice and WT littermates for our experiment. A53T α-syn heterozygous mice were randomly divided into two groups (n = 5, male). One group received intraperitoneal injection of Corynoxine B (Cory B) dissolved in 10% Solutol HS 15 (20 mg/kg), the other group received control reagent (10% Solutol HS 15), daily for 1 month. For the 10-month-old mice experiment, we selected 10-month-old heterozygous mice and WT littermates. A53T α-syn heterozygous mice were randomly divided into four groups (n = 5, 2 male and 3 female). Three groups received intraperitoneal injection of different dosages of Corynoxine B (Cory B) (5 mg/kg/day, 10 mg/kg/day and 20 mg/kg/day), while one group received control reagent (10% Solutol HS 15), for 1 month.[3]
For the 15-month-old mice experiment, we selected 15-month-old heterozygous mice and WT littermates. A53T α-syn heterozygous mice were randomly divided into three groups (n = 8, female). Two groups were given different dosages of Corynoxine B (Cory B) hydrochloride dissolved in saline (5 mg/kg; 20 mg/kg), and one group received control reagent (saline), once every 2 days for 2 consecutive months. All WT mice in the three experiments were given the corresponding control vehicle. For 15-month-old mice, behavior tests, constipation test and olfactory discrimination test were conducted during the last week. After finishing all the tests, mice were sacrificed and the brains were dissected for histology examination and biochemistry analysis. Each mouse brain was divided into two hemispheres. One half was fixed with 4% paraformaldehyde for immunostaining. The remaining half was divided into midbrain, prefrontal cortex, and other regions (three parts) and frozen at −80 °C.[3] |
| References |
|
| Additional Infomation |
Corynoxine B is a member of indolizines. It has a role as a metabolite.
Corynoxine B has been reported in Uncaria macrophylla and Mitragyna speciosa with data available. |
| Molecular Formula |
C22H28N2O4
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|---|---|
| Molecular Weight |
384.4687
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| Exact Mass |
384.204
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| CAS # |
17391-18-3
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| Related CAS # |
Corynoxine;6877-32-3
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| PubChem CID |
10091424
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| Appearance |
Typically exists as White to off-white solids
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
560.8±50.0 °C at 760 mmHg
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| Flash Point |
293.0±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.596
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| LogP |
3.31
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
663
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| Defined Atom Stereocenter Count |
4
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| SMILES |
O=C1[C@@]2(C3=C([H])C([H])=C([H])C([H])=C3N1[H])C([H])([H])C([H])([H])N1C([H])([H])[C@@]([H])(C([H])([H])C([H])([H])[H])[C@@]([H])(/C(=C(/[H])\OC([H])([H])[H])/C(=O)OC([H])([H])[H])C([H])([H])[C@]12[H]
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| InChi Key |
DAXYUDFNWXHGBE-XYEDMTIPSA-N
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| InChi Code |
InChI=1S/C22H28N2O4/c1-4-14-12-24-10-9-22(17-7-5-6-8-18(17)23-21(22)26)19(24)11-15(14)16(13-27-2)20(25)28-3/h5-8,13-15,19H,4,9-12H2,1-3H3,(H,23,26)/b16-13+/t14-,15+,19+,22-/m1/s1
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| Chemical Name |
methyl (E)-2-[(3R,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate
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| Synonyms |
Corynoxine B; 17391-18-3; CHEBI:70070; methyl (E)-2-[(3R,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate; CHEMBL1909423; SCHEMBL17531564;
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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 |
| 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) |
DMSO : ~83.33 mg/mL (~216.74 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.08 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6010 mL | 13.0049 mL | 26.0098 mL | |
| 5 mM | 0.5202 mL | 2.6010 mL | 5.2020 mL | |
| 10 mM | 0.2601 mL | 1.3005 mL | 2.6010 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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