Corynoxine B
(Synonyms: 柯诺辛碱 B) 目录号 : GC32826
柯诺辛B(CorynoxineB)是吲哚生物碱天然化合物，一个beclin-1-dependent自噬诱导剂。
Cas No.:17391-18-3
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Corynoxine B is an oxindole alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks (Gouteng in Chinese); a Beclin-1-dependent autophagy inducer. IC50 value:Target: Autophagy inducerin vitro: 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 [1].in vivo: Corynoxine B exhibited prolongation of the thiopental-induced hypnosis on oral administration in mice [2].
[1]. Song JX, et al. HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B. Autophagy. 2014 Jan;10(1):144-54. [2]. Sakakibara I, et al. Effect of oxindole alkaloids from the hooks of Uncaria macrophylla on thiopental-induced hypnosis. Phytomedicine. 1998 Apr;5(2):83-6.
| Cas No. | 17391-18-3 | SDF | |
| 别名 | 柯诺辛碱 B | ||
| Canonical SMILES | O=C(NC1=C2C=CC=C1)[C@]32[C@@](C[C@H](/C(C(OC)=O)=C\OC)[C@H](CC)C4)([H])N4CC3 | ||
| 分子式 | C22H28N2O4 | 分子量 | 384.47 |
| 溶解度 | DMSO: 83.33 mg/mL (216.74 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.601 mL | 13.0049 mL | 26.0098 mL |
| 5 mM | 0.5202 mL | 2.601 mL | 5.202 mL |
| 10 mM | 0.2601 mL | 1.3005 mL | 2.601 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。
Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy
Acta Pharmacol Sin 2022 Oct;43(10):2511-2526.PMID:PMC9525707DOI:10.1038/s41401-022-00871-0.
Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named Corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 μM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP+-treated PC12 cells, CB6 inhibited cell apoptosis and increased cell viability by inducing autophagy. In MPTP-induced mouse model of PD, oral administration of CB6 (10, 20 mg· kg-1· d-1, for 21 days) significantly improved motor dysfunction and prevented the loss of dopaminergic neurons in the striatum and substantia nigra pars compacta. Collectively, compound CB6 is a brain-permeable autophagy enhancer via PIK3C3 complex activation, which may help the prevention or treatment of PD.
Corynoxine B ameliorates HMGB1-dependent autophagy dysfunction during manganese exposure in SH-SY5Y human neuroblastoma cells
Food Chem Toxicol 2019 Feb;124:336-348.PMID:30578841DOI:10.1016/j.fct.2018.12.027.
Manganese (Mn) has recently come into the limelight as an important environmental risk factor for neurodegenerative disorders. Although multiple neurotoxicity of Mn have been extensively studied, the exact mechanism of Mn-induced autophagic dysregulation is still poorly understood. The main aim of this study was to explore the role of cytosolic high-mobility group box 1 (HMGB1)-dependent autophagy in Mn-induced autophagic dysregulation and neurotoxicity. SH-SY5Y cells were treated with culture solution (control) and three different concentrations of Mn (50, 100, and 200 μM) for 24 h to detect the effect of Mn on HMGB1-dependent autophagy. We found Mn could increase the HMGB1 mRNA level and its cytosolic translocation and dysregulate autophagy, and Mn-induced alpha-synuclein overexpression interfered with the interaction of HMGB1 and Beclin1, to subsequently promote Beclin1 binding to Bcl2. 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.
Separation and determination of corynoxine and Corynoxine B using chiral ionic liquid and hydroxypropyl-β-cyclodextrin as additives by field-amplified sample stacking in capillary electrophoresis
Electrophoresis 2018 Sep;39(17):2195-2201.PMID:29947080DOI:10.1002/elps.201800129.
A sensitive, fast, and effective method, field-amplified sample stacking (FASS) in capillary electrophoresis, has been established for the separation and determination of corynoxine and Corynoxine B. Hydroxypropyl-β-CD (HP-β-CD) and tetrabutylammonium-L-glutamic acid (TBA-L-Glu) were used as additives in the separation system. Electrokinetic injection was chosen to introduce sample from inlet at 10 kV for 50 s after a water plug (0.5 psi, 4 s) was injected to permit FASS. The running buffer (pH 6.1) was composed of 40 mM sodium dihydrogen phosphate solution, 130 mM HP-β-CD, and 10 mM TBA-L-Glu and the separation voltage was 20 kV. Under the optimum conditions, corynoxine and Corynoxine B were successfully enriched and separated within 12 min and the sensitivity was improved approximately by 700-900 folds. Calibration curves were in a good linear relationship within the range of 62.5-5.00 × 103 ng/mL for both corynoxine and Corynoxine B. The limits of detection (S/N = 3) and quantitation (S/N = 10) were 14.9, 45.2 ng/mL for corynoxine and 11.2, 34.5 ng/mL for Corynoxine B, respectively. Finally, this method was successfully applied for the determination of corynoxine and Corynoxine B in the stems with hooks of Uncaria rhynchophylla and its formulations.
HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression: a process modulated by the natural autophagy inducer Corynoxine B
Autophagy 2014 Jan;10(1):144-54.PMID:24178442DOI:10.4161/auto.26751.
SNCA/α-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNCA has been shown to impair macroautophagy in mammalian cells and in transgenic mice. In this study, we monitored the dynamic changes in autophagy process and confirmed that overexpression of both WT and SNCA(A53T) inhibits autophagy in PC12 cells in a time-dependent manner. Furthermore, we showed that SNCA binds to both cytosolic and nuclear high mobility group box 1 (HMGB1), impairs the cytosolic translocation of HMGB1, blocks HMGB1-BECN1 binding, and strengthens BECN1-BCL2 binding. Deregulation of these molecular events by SNCA overexpression leads to autophagy inhibition. Overexpression of BECN1 restores autophagy and promotes the clearance of SNCA. siRNA knockdown of Hmgb1 inhibits basal autophagy and abolishes the inhibitory effect of SNCA on autophagy while overexpression of HMGB1 restores autophagy. 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.
Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway
J Neuroimmune Pharmacol 2014 Jun;9(3):380-7.PMID:24522518DOI:10.1007/s11481-014-9528-2.
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of the autophagy-lysosomal system has been linked to its accumulation. In our previous study, we identified an oxindole alkaloid Corynoxine B (Cory B), isolated from Uncaria rhynchophylla (Miq.) Jacks (Gouteng in Chinese), as a Beclin-1-dependent autophagy inducer. In this work, we show that Cory, an enantiomer of Cory B, also induces autophagy in different neuronal cell lines, including N2a and SHSY-5Y cells, which is paralleled with increased lysosomal enzyme cathepsin D. In vivo, Cory promotes the formation of autophagosomes in the fat bodies of Drosophila. By inducing autophagy, Cory promotes the clearance of wild-type and A53T α-syn in inducible PC12 cells. Interestingly, different from its enantiomer Cory B, Cory induces autophagy through the Akt/mTOR pathway as evidenced by the reduction in the levels of phospho-Akt, phospho-mTOR and phospho-p70 S6 Kinase. Collectively, our findings provide experimental evidence for developing Cory as a new autophagy enhancer from Chinese herbal medicine, which may have potential application in the prevention or treatment of PD.