Synonym name: 2,3,9,10-Tetramethoxy-13-methylberbine, 8CI; Corydalis A
Catalogue No.: BP0396
Cas No.: 518-69-4
Formula: C₂₂H₂₇NO₄
Mol Weight: 369.461
Botanical Source: Alkaloid from Corydalis tuberosa and many other Corydalis spp. (Fumariaceae)

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

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

HPLC of Corydaline

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

Introduction/Overview

Corydaline (CAS No.: 518-69-4) is an important natural isoquinoline alkaloid, mainly isolated from the traditional Chinese medicinal material Corydalis (Corydalis yanhusuo W.T. Wang). As a widely used blood-activating and pain-relieving herb in traditional Chinese medicine, research on its active ingredients has been ongoing for decades. Corydalis Yanhusuojia, as one of its key active ingredients, has attracted widespread attention due to its multi-target and multifunctional pharmacological activity. In recent years, with in-depth research in neurological diseases, pain management, and viral infections, Corydalis has demonstrated unique pharmacological potential, especially in analgesia, opioid receptor regulation, antiviral, and anti-angiogenesis with remarkable biological activity, making it a hot topic in pharmacological research of natural products.

This paper aims to systematically review the chemical structure and physicochemical properties of Corydalis methylene, plant origin, and extraction methods, with a focus on its pharmacological activity, mechanism of action, and molecular targets, exploring its pharmacokinetic characteristics in combination with druggability parameters, and finally looking ahead to its clinical application prospects and future research directions, providing theoretical basis and research ideas for natural product pharmacology and new drug development.

Chemical structure and physicochemical properties

Corydalis belongs to the isoquinoline alkaloids class, with a molecular formula of C_22H_27NO_4 and a molecular weight of 369.45. Its structural features include a nitrogen-containing isoquinoline backbone connected to multiple methoxy and hydroxyl substituents, giving it certain polarity and biological activity. The LogP value of Corydalis is 3.5, indicating moderate lipid solubility, which is beneficial for penetrating cell membranes and the blood-brain barrier (BBB). The TPSA (topological pole surface area) is 55.83 Ų, and the number of hydrogen bond receptors is 5, all meeting the physicochemical parameters required for drug molecules to stimulate the central nervous system.

The physicochemical properties of corydalisin give it good bioavailability and tissue distribution in the body, especially its strong penetration into the central nervous system, laying the foundation for its development as a drug for treating neurological diseases. However, safety indicators such as hepatotoxicity, cardiotoxicity, hERG channel inhibition, and genotoxicity (Ames test) remain unclear and require further systematic evaluation.

Plant Origins and Extraction Methods

Corydalis yanhusuo mainly originates from Corydalis yanhusuo, a perennial herbaceous plant of the genus Corydalis in the poppy family, widely distributed in southern China and Southeast Asia. The tuberous root of Corydalis is a traditional Chinese medicinal herb with effects of promoting blood circulation, removing blood stasis, and relieving pain. As one of its main alkaloid components, the content of Corydalisin is greatly affected by the planting environment, harvest time, and processing technology.

Traditional methods for extracting Corydalis mainly include organic solvent extraction and chromatographic separation. Common extraction solvents include ethanol, methanol, and their aqueous solutions, which are extracted using reflux or ultrasound assistance to improve extraction efficiency. The extract is purified by acid-base adjustment, liquid-liquid distribution, and column chromatography (such as silica gel columns and C18 reversed-phase columns), and finally identified and quantified by high-performance liquid chromatography (HPLC) or mass spectrometry (MS). In recent years, new technologies such as supercritical CO_2 extraction and microwave-assisted extraction have also been applied to the extraction of Corydalis chloride, significantly improving extraction efficiency and purity.

Pharmacological activity research

Corydalis exhibits a variety of significant pharmacological activities, covering areas such as nervous system regulation, antiviral, anti-angiogenic effects, and anti-allergy.

1. Analgesic effect

As an μ-opioid receptor (OPRM1) agonist, Yanhusuojia has a Ki value of 1.23 μM, indicating strong opioid-like activity. By activating μ-opioid receptors, corydalis can regulate pain signal transmission in the central and peripheral nervous systems, exerting its analgesic effect. Additionally, corydalis may further alleviate pain and inflammatory responses by modulating pain-related ion channels such as TRPV1 and TRPA1, and by inhibiting synthases of inflammatory mediators like PTGS1 (COX-1) and PTGS2 (COX-2).

2. Anticholinesterase activity

Corydalis has an inhibitory effect on acetycholinesterase (AChE), with an IC50 of about 226 μM. Although its inhibitory activity is weak, its AChE inhibitory effect suggests its potential application value in cognitive impairment and neurodegenerative diseases.

3. Antiviral effects

Corydalis has a significant inhibitory effect on enterovirus 71 (EV71), with an IC50 of 25.23 μM. EV71 is the main pathogen causing hand, foot, and mouth disease and severe neurological complications. Corydalisin demonstrates strong antiviral potential by interfering with viral replication.

4. Anti-angiogenesis and anti-allergy

Corydalisin can inhibit the proliferation of vascular endothelial cells and the formation of new angiogenesis, demonstrating anti-angiogenic activity, which may help regulate the tumor microenvironment and control inflammation. At the same time, its anti-allergic effect reduces allergic reactions by inhibiting mast cell degranulation and the release of inflammatory mediators.

5. Regulation of gastrointestinal motility

Corydalis promotes gastric emptying and improves gastrointestinal motility disorders, possibly by regulating the contraction of gastrointestinal smooth muscle and neural regulation, offering potential therapeutic value for gastrointestinal dysfunction.

Mechanism of action and molecular targets

The multi-target mechanism of corydalisin forms the basis of its multiple pharmacological effects. Its main targets include:

• μ-opioid receptor (OPRM1): Corydalis acts as an agonist, activating this receptor and inhibiting pain conduction through the G protein-coupled signaling pathway, exerting analgesic effects.
• Acetylcholinesterase (AChE): Inhibits AChE activity, prolongs the duration of acetylcholine action in the synaptic cleft, and may improve cognitive function.
• TRPV1 and TRPA1 ion channels: regulate pain perception and inflammatory responses; corydalis may reduce pain and inflammation by inhibiting these channels.
• Cyclooxygenase (PTGS1/COX-1, PTGS2/COX-2): Inhibits prostaglandin synthesis, reduces inflammation and pain.
• Endogenous opioid system-related receptors (OPRD1, OPRK1): May be involved in the analgesic and neuromodulatory effects of corydalisin.
• Dopamine receptor D2 (DRD2) and serotonin transporter 5-hydroxytryptamine (SLC6A4): may affect mood and neurotransmission, indirectly participating in analgesic and antidepressant effects.
• Viral replication-related targets: Corydalis inhibits viral replication by interfering with the replication mechanism of the EV71 virus.

The synergistic effect of these multiple targets enables Corydalis to demonstrate comprehensive efficacy in pain, neuroprotection, and antiviral aspects.

Druggability evaluation and pharmacokinetics

The druggability parameters of Corydalis show that it has good potential for drug development. The molecular weight of 369.45 meets the Lipinski rule, with a LogP of 3.5, indicating moderate lipid solubility, which is beneficial for cell membrane permeability and oral absorption. The TPSA is 55.83 Ų, below 90 Ų, supporting its ability to penetrate the blood-brain barrier and meeting the requirements for central nervous system activity. It has 5 hydrogen bond receptors, making it suitable for stable binding to target proteins.

Currently, pharmacokinetic data on corydalisin are limited. Some in vivo studies show that its oral bioavailability is good, allowing effective distribution into brain tissue to support its nervous system effects. However, key parameters such as hepatic metabolic pathways, clearance rate, and half-life still require systematic study. In terms of safety, hepatotoxicity, cardiotoxicity (such as hERG channel inhibition), and genotoxicity remain unclear, requiring comprehensive toxicological evaluation.

Prospects and outlooks for clinical applications

As a natural isoquinoline alkaloid, corydalisin has broad clinical application prospects thanks to its multi-target and multifunctional pharmacological properties.

Analgesic treatment

Corydalis demonstrates excellent analgesic potential by activating μ-opioid receptors and modulating various pain-related targets, making it especially suitable for managing chronic, neuropathic, and inflammatory pain. Its natural origin and multi-target effects are expected to reduce dependence and side effects of traditional opioids, making it a candidate for new analgesic drugs.

Neurological diseases

Its AChE inhibitory effect suggests the potential application of corydalis in Alzheimer's disease and other cognitive impairment disorders. Combining its anti-inflammatory and neuroprotective effects, Corydalis is expected to become a multi-target neuroprotectant.

Antiviral therapy

The inhibitory effect against enterovirus 71 expands the development direction of antiviral drugs for Corydalis Yanhusuo, especially showing potential value in the prevention and treatment of hand, foot, and mouth disease and related neurological complications.

Other potential applications

Anti-angiogenic and anti-allergic effects offer new ideas for tumor treatment and allergic diseases. Its ability to promote gastric emptying also gives it promising application in gastrointestinal motility disorders.

Future research should focus on optimizing the pharmacokinetics, evaluating safety, and validating preclinical animal models of corydalisin, combining modern drug design techniques such as structural modification and nanocarrier delivery to enhance its efficacy and safety, and promote its clinical translation.

Conclusion

As an isoquinoline alkaloid derived from the traditional Chinese medicine Yanhusuo, Yanhusuo Methyl demonstrates broad pharmacological application potential due to its unique chemical structure and multi-target pharmacological activity. Its research progress in analgesia, neuroprotection, antiviral, and anti-angiogenesis provides valuable scientific evidence for the development of natural product new drugs. Although current data on its pharmacokinetics and safety are not yet complete, with the development of modern pharmacology and medicinal chemistry technologies, corydalis is expected to become an important candidate for multifunctional drugs in the future. Systematic and in-depth mechanistic research and preclinical evaluation will be key to advancing its clinical application, injecting new vitality into the field of natural product pharmacology.