Product name: (-)-Corynoxidine
Synonym name:
Catalogue No.: BP4076
Cas No.: 57906-85-1
Formula: C₂₁H₂₅NO₅
Mol Weight: 371.433
Botanical Source: Corynoxidine；Tetrahydropalmatine N-oxide
Physical Description:
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

As the incidence of neurodegenerative diseases continues to rise, the search for efficient and safe neuroprotective agents has become an important direction for contemporary drug development. Natural products, due to their structural diversity and broad bioactivity, have become valuable resources in the field of neuroprotection. (-)-Corynoxidine (CAS No.: 57906-85-1), a natural alkaloid with significant neuroprotective potential, has attracted widespread attention in recent years. Its targets include BCL2, APP, BACE1, MAPT, SIRT1, MAPK1, ACHE, CASP3, SNCA, and NRF2, among other key proteins closely related to neurodegenerative diseases, demonstrating multiple mechanisms regulating neuronal survival, antioxidant stress, and suppressing neuroinflammation. This article aims to systematically review the chemical structure, origin, pharmacological activity, and mechanism of action of (-)-Corynoxidine, evaluate its druggability and clinical application prospects, and provide a theoretical basis for subsequent research and drug development.

Chemical structure and physicochemical properties

(-)-Corynoxidine is a natural alkaloid with a molecular weight of 371.4330, belonging to the isoquinoline class of compounds. Its molecular structure contains multiple cyclic structures and oxidation groups, giving it a unique spatial configuration and chemical activity. The LogP value is 1.5837, indicating moderate lipid solubility, which facilitates penetration of lipid bilayer membranes. The polar surface area (TPSA) was 59.98 Ų, indicating a good balance between cell membrane permeability and target binding. Water solubility is 27.0441 mg/mL, indicating a certain degree of aqueous solubility, which is beneficial for absorption and distribution in the body. Importantly, (-)-Corynoxidine has a high blood-brain barrier penetration ability, making it suitable for treating central nervous system diseases. Additionally, this compound did not exhibit hERG channel inhibitory activity, reducing the potential risk of cardiotoxicity; The Ames test result was 0.0, indicating a low genotoxicity risk and meeting safety requirements.

Plant Origins and Extraction Methods

(-)-Corynoxidine is mainly found in various Chinese medicinal materials, especially from plants of the Fangziaceae family such as Uncaria rhynchophylla and other related plants. Uncaria is widely used in traditional Chinese medicine to treat headaches, dizziness, and neurological disorders. Its active ingredients include various alkaloids, among which (-)-Corynoxidine is one of the important representatives.

The extraction method typically uses alcohol solvents (such as methanol or ethanol) for crude extraction, followed by liquid-liquid separation, column chromatography (such as silica gel columns, C18 reversed phase columns), and high-performance liquid chromatography (HPLC) for separation and purification. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity. Purified (-)-Corynoxidine can be structured by mass spectrometry and nuclear magnetic resonance (NMR) technology to ensure its chemical purity and structural integrity.

Pharmacological activity research

A large number of in vivo and in vitro experiments have shown that (-)-Corynoxidine has significant neuroprotective effects. Its main pharmacological activities include:

1. Antioxidant stress: By activating the NRF2 signaling pathway, it enhances the expression of intracellular antioxidant enzymes, lowers reactive oxygen species (ROS) levels, and alleviates oxidative damage.

2. Inhibits neuroinflammation: It can downregulate the expression of pro-inflammatory cytokines, suppress the activation of microglia and astrocytes, and alleviate neuroinflammatory responses.

3. Anti-apoptotic effect: Regulates the expression of BCL2 family proteins, inhibits CASP3 activation, and protects neurons from apoptosis damage.

4. Regulates neurotransmitter enzyme activity: Inhibits acetylcholinesterase (ACHE) activity, increases acetylcholine levels, and improves cognitive function.

5. Inhibition of amyloid production: By regulating APP and BACE1 expression, it reduces β-amyloid protein production and slows the pathological progression of Alzheimer's disease.

6. Stabilizes tubulin: acts on MAP (tau protein) to prevent abnormal phosphorylation and maintain nerve fiber stability.

7. Regulation of cell signaling pathways: Affects signaling molecules such as MAPK1 and SIRT1, promoting cell survival and metabolic homeostasis.

These multi-target, multi-mechanism pharmacological properties give (-)-Corynoxidine good therapeutic potential in neurodegenerative disease models.

Mechanism of action and molecular targets

(-)-Corynoxidine achieves its neuroprotective effects through multi-target synergistic action, with main mechanisms including:

• BCL2 and CASP3 regulate the apoptotic pathway :(-)-corynoxidine upregulate the anti-apoptotic protein BCL2, inhibit the activation of the active caspase CASP3, block the neuronal apoptosis cascade, and protect cell survival.

• APP and BACE1 inhibit amyloid production: By inhibiting the activity of the β-secretase BACE1, it reduces abnormal cleavage of APP, lowers β-amyloid protein deposition, and slows the pathological progression of Alzheimer's disease.

• MAPT regulates abnormal phosphorylation of tau protein :(-)-corynoxidine to stabilize tau protein structure, prevent abnormal aggregation, maintain nerve fiber integrity, and reduce neuronal damage.

• SIRT1 activates the cellular protection pathway: Activates SIRT1 deacetylase, regulates cellular metabolism and antioxidant responses, and promotes neuronal survival and functional recovery.

• MAPK1 signaling pathway regulation: regulates cellular stress responses and inflammatory signals, reducing neuroinflammation and cell damage.

• ACHE inhibits and improves cognitive function: By inhibiting acetylcholinesterase, it extends the duration of acetylcholine's action in the synaptic cleft, thereby enhancing cognitive abilities.

• SNCA regulates α-synuclein aggregation: slows abnormal aggregation of α-synuclein associated with Parkinson's disease and protects dopaminergic neurons.

• NRF2 activates the antioxidant defense system: promotes the expression of intracellular antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD), enhancing cells' resistance to oxidative stress.

In summary, (-)-Corynoxidine achieves multi-level protection of neurons by regulating multiple signaling pathways related to neurodegenerative diseases.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, (-)-Corynoxidine exhibits good drug properties. Its molecular weight (371.4330) complies with the Lipinski rule and is suitable for oral absorption. A moderate LogP value (1.5837) indicates good lipid solubility, which facilitates cell membrane penetration. The TPSA is 59.98 Ų, supporting its good oral bioavailability and blood-brain barrier penetration, which has been validated through both in vitro and in vivo models.

Moderate water solubility (27.0441 mg/mL), which is beneficial for formulation development and in vivo distribution. Importantly, this compound does not inhibit hERG channels, reducing the risk of cardiotoxicity; The Ames test result was negative, indicating a low genotoxicity risk and good safety.

Preliminary pharmacokinetic studies indicate that (-)-Corynoxidine is rapidly absorbed orally, has a moderate plasma half-life, and can effectively enter the central nervous system to achieve therapeutic concentrations. Its metabolic pathway mainly involves hepatic enzyme systems, and the metabolites still require further identification. No significant risk of drug interactions and possesses good pharmacokinetic characteristics.

Prospects and outlooks for clinical applications

Due to its multi-target neuroprotective effects, (-)-Corynoxidine shows broad application prospects in the treatment of Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Its combined antioxidant, anti-anti-inflammatory, and anti-apoptotic effects are expected to slow disease progression and improve patients' cognitive and motor functions.

Future research should focus on:

1. Preclinical safety and toxicological assessment: Systematic evaluation of the safety of long-term medication, clarifying the maximum tolerated dose and potential toxicity.

2. Pharmacokinetic and pharmacodynamic relationship studies: In-depth analysis of metabolic pathways and duration of drug effects in vivo to optimize administration regimens.

3. Clinical trial design: Conduct early clinical trials to verify efficacy and safety in patients with neurodegenerative diseases.

4. Structural optimization and derivative development: Chemical modification enhances activity and selectivity, reducing potential side effects.

5. Combination therapy strategy: Explore combined use with existing therapeutic drugs to maximize synergistic effects.

In summary, (-)-Corynoxidine, as a natural product with multiple neuroprotective mechanisms, has the potential to become a novel neuroprotective drug and warrants further research and development.

Conclusion

(-)-Corynoxidine, a natural alkaloid derived from traditional Chinese medicine, has become a strong candidate in the field of neurodegenerative disease treatment due to its excellent druggability, multi-target neuroprotective effects, and safety advantages. By regulating multiple key pathways such as apoptosis, oxidative stress, inflammatory response, and neurotransmitter metabolism, it demonstrates significant neuroprotective effects. In the future, combining modern drug development technologies and systematically conducting pharmacological, toxicological, and clinical research is expected to promote their application into clinical practice, bringing new treatment options for patients with neurodegenerative diseases.