Product name: Corynoline
Synonym name:
Catalogue No.: BP0398
Cas No.: 18797-79-0
Formula: C₂₁H₂₁NO₅
Mol Weight: 367.401
Botanical Source: Corydalis bungeana Turcz.
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.

Description:

Corynoline is a reversible and noncompetitive inhibitor of acetylcholinesterase(AChE) with the IC50 value of 30.6 microM, which exhibits the potent anti-inflammatory and/or immunosuppressive activity, the potent inhibitory activity of corynoline for the ICAM-1/LFA-1 adhesion and would be important on developing the clinically usable drugs for the inflammatory diseases.

References:

Bioorg Med Chem. 2005 Mar 1;13(5):1867-72.    

Cell adhesion inhibitory activity of (d)-corynoline, a hexahydrobenzo[c]phenanthridine-type alkaloid, and its structure-activity relationship, studied by X-ray crystal structure analysis and molecular docking study.   

Corynoline (1), a hexahydrobenzo[c]phenanthridine-type alkaloid, exhibited the concentration-dependent inhibition for the adhesion of human polymorphonuclear leukocyte and eosinophil to human umbilical vein cultured endothelial cell in the concentration range of showing no significant cytotoxicity for the cell: IC(50) value=72.4 microM for (d)-1 and 156.7 microM for (l)-1. This shows the potent anti-inflammatory and/or immunosuppressive activity of 1. 

METHODS AND RESULTS:

To elucidate possible structure-activity relationship, the conformational/structural feature of (d)-1 was investigated by X-ray crystal structure analysis and molecular orbital energy calculations, and the docking study was performed for its interaction with the D1-domain of ICAM-1 (intracellular adhesion molecule-1). A plausible model was proposed, in which all polar atoms of (d)-1 are linked by hydrogen bonds or electrostatic interactions with the functional residues of ICAM-1, that have been supposed to be necessary for the binding with LFA-1 (leukocyte function-associated antigen-1). 

CONCLUSIONS:

This suggests the potent inhibitory activity of 1 for the ICAM-1/LFA-1 adhesion and would be important on developing the clinically usable drugs for the inflammatory diseases.    

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

Introduction/Overview

Corynoline, CAS number 18797-79-0, is a natural alkaloid derived from the traditional Chinese medicinal material Corydalis bungeana Turcz. As an orally active acetylcholinesterase (AChE) inhibitor, Zijinling shows significant potential in neuroprotective, anti-inflammatory, antitumor, and analgesic pharmacological activities. In recent years, with the deepening development of natural product pharmacology, Zijin Ling has gradually become a hot molecule in research on tumors, inflammatory pain, and other diseases due to its multi-target and multi-mechanism pharmacological properties. This paper aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Zijin Ling, providing a theoretical foundation and research direction for its subsequent development.

Chemical structure and physicochemical properties

Zijinling is an isoquinoline alkaloid with a molecular formula C22H23NO5 and a molecular weight of 383.39. Its structural features mainly include a polycyclic isoquinoline framework containing multiple hydroxyl and methoxy substituents, which give it good hydrophilicity and the ability to form intermolecular hydrogen bonds. The LogP value of Zijinling is 2.46, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 82.85 Ų, and it has 6 hydrogen bond acceptors, indicating certain polarity, which may affect its bioavailability and blood-brain barrier penetration ability. Currently, safety indicators such as blood-brain barrier permeability, hepatotoxicity, cardiotoxicity, and hERG channel inhibition of Zijinling remain unclear and require further systematic evaluation.

The chemical structure of Zijinling is as follows (illustrative example):

  [异喹啉核心结构]
  - 多羟基和甲氧基取代
  - 分子量：383.39
  - LogP：2.46
  - TPSA：82.85
  - 氢键受体数：6

Its structural complexity and diverse functional groups provide the molecular basis for its multi-target action.

Plant Origins and Extraction Methods

Corydalis is mainly found in plants of the genus Corydalis, especially Corydalis bungeana and related species. Violet is a plant of the Ranunculaceae family, widely distributed in northern and northeastern China. In traditional Chinese medicine, it is often used to clear heat, detoxify, reduce swelling, and relieve pain.

The extraction of Zijin Ling usually follows these steps:

1. Raw material preparation: Collect the dried above-ground part or whole Violet violet and crush it into coarse powder.
2. Solvent extraction: Use ethanol or methanol for reflux extraction, usually taking 2-4 hours, with 2-3 repeated extractions to improve yield.
3. Concentration and separation: Concentrate the extract to an appropriate amount and use liquid-liquid partitioning to remove fat-soluble impurities.
4. Column chromatography purification: Using silica gel column chromatography or high-performance liquid chromatography (HPLC) methods, combined with gradient elution, purification of Zijinling.
5. Structure identification: Confirm compound structure by mass spectrometry (MS), nuclear magnetic resonance (NMR), and infrared spectroscopy (IR).

In recent years, new technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been applied to the extraction of Zijinling, significantly improving extraction efficiency and purity.

Pharmacological activity research

As a versatile natural product, Zijinling has demonstrated significant biological activity in various pharmacological models, mainly including:

1. Acetylcholinesterase (AChE) inhibitory activity

The inhibitory effect of Zijinling on AChE is the basis of its neuroprotective effect. In vitro experiments showed that Zijinling inhibits AChE at about 30.6 μM, indicating moderate inhibition activity. AChE inhibitors have significant value in the treatment of neurodegenerative diseases such as Alzheimer's disease, and thus Zijinling is regarded as a potential neuroprotective agent.

2. Anti-inflammatory activity

Zijinling has demonstrated good anti-inflammatory effects across various inflammation models. Its mechanism mainly involves inhibiting the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6, thereby reducing inflammatory responses. In vivo experiments have shown that Zijin Ling can significantly reduce pain behaviors in inflammatory pain models, suggesting its potential in treating inflammatory pain.

3. Antitumor activity

Zijinling exhibits effects in lung cancer and other tumor cell lines that inhibit proliferation and induce apoptosis. Research shows that Zijin Ling can regulate various tumor-related signaling pathways, including BCL2, STAT3, RELA (NF-κB subunit), members of the MAPK family (MAPK1, MAPK8), and PI3K/AKT pathways, exerting anti-tumor effects. Additionally, the mechanism by which Zijin Ling induces tumor cell apoptosis is closely related to the activation of apoptosis-related enzymes such as CASP9.

4. Analgesic effect

Zijinling demonstrates analgesic effects in both neuropathic and inflammatory pain models. Its analgesic mechanism may be related to inhibiting the release of inflammatory mediators and regulating neurotransmitters, but the specific mechanism still requires further elucidation.

Mechanism of action and molecular targets

The multi-target mechanism of Zijinling forms the molecular basis of its multiple pharmacological activities. Through molecular docking, cell experiments, and animal model studies, Zijin Ling mainly targets the following:

• BCL2: As an anti-apoptotic protein, downregulation of BCL2 helps induce tumor cell apoptosis. Zijinling can regulate BCL2 expression and promote programmed cell death.
• STAT3: As a transcription factor, STAT3 regulates various genes for cell proliferation and immune responses. Zijin Ling inhibits the STAT3 signaling pathway, suppressing tumor growth and inflammatory responses.
• ESR2 (estrogen receptor β): Zijinling may influence cell proliferation and differentiation by regulating ESR2-mediated signaling pathways.
• MAPT (microtubule-associated protein Tau): Associated with cytoskeletal stability; Zijin may affect nerve cell function.
• PIK3CG (PI3Kγ) :P key member of the I3K/AKT signaling pathway, which participates in cell survival and metabolic regulation by regulating this pathway.
• RELA (NF-κB p65 subunit): Zijin Ling inhibits NF-κB signaling, reduces inflammatory responses, and reduces tumor progression.
• MAPK1 (ERK2) and MAPK8 (JNK1): regulate cell proliferation, differentiation, and apoptosis. Zijin Ling exerts antitumor and anti-inflammatory effects by modulating the MAPK signaling pathway.
• CASP9: A key mitochondrial apoptotic protein, Zijinling activates CASP9 to promote apoptosis.
• PPARG (Peroxisome Proliferator-Activated Receptor γ): Regulates metabolism and inflammation. Zijinling may exert anti-inflammatory and metabolic regulatory effects through PPARG.

In summary, Zijinling exerts its broad pharmacological effects through multi-target and multi-pathway coordinated regulation.

Druggability evaluation and pharmacokinetics

The druggability parameters of Zijinling indicate that it has certain potential for drug development:

• The molecular weight (383.39) fits the ideal range of Lipinski's rules, which is beneficial for oral absorption.
• LogP (2.46) was moderate, indicating that Zijin Ling has good lipid solubility, which facilitates cell membrane penetration.
• TPSA (82.85 Ų) suggests moderate polarity, which may affect its oral bioavailability and blood-brain barrier penetration.
• The number of hydrogen bond receptors (6) is moderate, which helps molecules form stable binding with target proteins.

However, key pharmacokinetic and toxicological indicators of Zijinling, such as blood-brain barrier permeability, safety (hepatotoxicity, cardiotoxicity, hERG channel inhibition), and genotoxicity (Ames assay), remain unclear, limiting its preclinical development. In the future, in vivo pharmacokinetic studies (such as absorption, distribution, metabolism, excretion of ADME) and systemic toxicological evaluation are needed to comprehensively evaluate its safety and efficacy.

Prospects and outlooks for clinical applications

As a versatile natural product, Zijinling has broad clinical application potential:

1. Neurodegenerative diseases: Its AChE inhibitory activity makes it a potential therapeutic candidate for cognitive impairment diseases such as Alzheimer's.
2. Tumor Therapy: By regulating multiple tumor signaling pathways, Zijinling holds promise as an adjunctive therapy for solid tumors such as lung cancer, especially in combination chemotherapy or targeted therapy.
3. Inflammatory Diseases and Pain Management: The anti-inflammatory and analgesic effects of Zijinling offer new treatment approaches for inflammatory pain, rheumatoid arthritis, and other conditions.
4. Multi-target drug development: The multi-target characteristics of Zijin Ling align with current trends in precision medicine and multi-target drug design, and are expected to be developed into compound mechanism therapies.

Future research should focus on pharmacokinetic optimization and structural modification of Zijin Ling to enhance its efficacy and safety, as well as the development of preclinical animal models and early clinical trials. At the same time, by integrating modern molecular biology and medicinal chemistry techniques, the mechanism of action is deeply analyzed to promote the clinical translation of Zijin Ling.

Conclusion

As a natural product with multiple pharmacological activities, Zijinling demonstrates broad application potential in neuroprotection, anti-inflammatory, anti-tumor, and analgesic fields. Its unique chemical structure and multi-target mechanism of action provide a valuable molecular template for the development of natural product drugs. Although the safety and pharmacokinetic data of Zijinling are still incomplete, as research deepens, its value as a novel drug candidate molecule is becoming increasingly prominent. In the future, through systematic pharmacological research and preclinical evaluations, Zijin Ling is expected to become a new hope for treating various diseases and promote innovative development in natural product pharmacology.