Synonym name: 2,3:9,10-Bismethylenedioxyprotoberberine
Catalogue No.: BP0390
Cas No.: 3486-66-6
Formula: C₁₉H₁₄NO₄
Mol Weight: 320.324
Botanical Source: Quaternary alkaloid from Coptis japonica (Ranunculaceae) and many other spp., mostly in the Papaveraceae and 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 Coptisine

HNMR of Coptisine

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

Introduction/Overview

Coptis chinensis is a typical isoquinoline alkaloid, which was first isolated from the Chinese medicinal herb Coptis chinensis Franch. As one of the main active ingredients of Huanglian, berberine is widely used in traditional Chinese medicine for clearing heat and detoxifying, antibacterial and anti-inflammatory purposes. In recent years, with the advancement of natural product pharmacology and molecular biology techniques, the pharmacological activity and mechanism of action of berberine have gradually been revealed, especially in the fields of drug-resistant bacterial infections and immune regulation, showing significant potential.

Huanglian alkaloid, as an effective non competitive indoleamine 2,3-dioxygenase (IDO) inhibitor, exhibits good enzyme inhibitory activity with a Ki value of 5.8 μ M and an IC50 value of 6.3 μ M. As an important regulator of immune escape, IDO plays a key role in tumor immunosuppression and infectious diseases. Therefore, the IDO inhibitory function of coptidine provides a theoretical basis for its anti-tumor and anti infection research. In addition, berberine exhibits potential inhibitory effects on various drug-resistant bacterial targets such as DNA gyrase A (GYRA) and dihydrofolate reductase (DHFR), indicating its potential application value in the field of anti drug-resistant bacterial infections.

This article will systematically review the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity and mechanism of action, pharmacological evaluation and pharmacokinetic characteristics of coptisine, and explore its clinical application prospects and future research directions, aiming to provide scientific basis and reference for the development and utilization of coptisine.

Chemical structure and physicochemical properties

Coptis alkaloids have a molecular formula of C19H14NO4 and a molecular weight of 320.32. Its structure belongs to the isoquinoline alkaloids, specifically a tetracyclic isoquinoline skeleton containing multiple benzene rings and methoxy substituents. The chemical structure contains 5 hydrogen bond acceptors, with a polar surface area (TPSA) of 64.88 Å ² and a LogP value of approximately 0.10, indicating low lipid solubility and some hydrophilicity.

The structural characteristics of berberine determine its biological activity and pharmacokinetic properties. A lower LogP value suggests that its distribution in vivo may be biased towards plasma and extracellular fluid, and its ability to penetrate the blood-brain barrier is weaker (predicted as Low). In addition, the molecular structure of berberine is stable and easy to separate and purify through various chromatographic techniques.

The summary of physical and chemical properties is as follows:

• Molecular weight: 320.32
• LogP：0.10
• Polar surface area (TPSA): 64.88 Å ²
• Number of hydrogen bond acceptors: 5
• Blood brain barrier permeability: low
• Stability: Stable chemical structure, easy to extract and purify

These properties provide fundamental data for the drug design and formulation development of berberine.

Plant sources and extraction methods

Huanglian alkaloids are mainly found in plants of the Coptis genus, with the highest content found in the traditional Chinese medicine Coptis chinensis Franch. Huanglian is a perennial herbaceous plant of the genus Huanglian in the Ranunculaceae family, widely distributed in southwestern China. In addition to Huanglian, Huanglian alkaloids are also present in other Huanglian plants and some traditional Chinese medicine formulas.

extraction method

The extraction of berberine usually involves the following steps:

1. Raw material pretreatment Crush the dried rhizomes of Huanglian into fine powder to increase the surface area for solvent penetration.
2. Solvent extraction Acidic ethanol (such as 0.1% hydrochloric acid ethanol) or methanol are commonly used as extraction solvents, and the extraction time is generally 1-3 hours through reflux extraction or ultrasound assisted extraction.
3. Crude extract concentration After filtration, the extract is concentrated under reduced pressure to remove the solvent and obtain a concentrate.
4. Separation and purification：
5. Remove impurities through acid-base precipitation method.
6. Further separation of berberine using column chromatography techniques such as silica gel columns and C18 reverse phase columns.
7. High performance liquid chromatography (HPLC) is used for purity detection and quantitative analysis.
8. Crystallization Purified coptisine can be obtained into high-purity crystalline products through recrystallization.

In recent years, green extraction techniques such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to the extraction of coptisine, improving extraction efficiency and environmental friendliness.

Pharmacological activity research

Huanglian alkaloid, as an important active ingredient in Huanglian, exhibits various pharmacological activities, covering fields such as antibacterial, anti-inflammatory, anti-tumor, and immune regulation.

Antibacterial activity

Berberine has inhibitory effects on various Gram positive and Gram negative bacteria, especially on drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Klebsiella pneumoniae. Its targets include:

• DNA gyrase A (GYRA): affects bacterial DNA replication and transcription.
• Dihydrofolate reductase (DHFR): interferes with bacterial folate metabolism.
• Other related targets such as GYPB, MECA, PENA, etc. are involved in bacterial cell wall synthesis and metabolic processes.

These mechanisms of action make berberine a potential candidate drug for combating drug-resistant bacterial infections.

Antitumor and immune regulation

As a non competitive inhibitor of IDO, berberine can inhibit the IDO mediated tryptophan metabolism pathway, reverse the immunosuppressive state in the tumor microenvironment, and promote T cell immune response. The inhibitory activity of IDO makes berberine have potential application value in the field of tumor immunotherapy.

In addition, berberine also exhibits anti-inflammatory effects by downregulating the expression of inflammatory factors such as TNF - α and IL-6, and reducing tissue inflammatory responses.

Other pharmacological effects

The study also found that berberine has multiple biological effects such as antioxidant, neuroprotective, and blood glucose and lipid regulation, demonstrating its multi-target and multi pathway pharmacological properties.

Mechanism of action and molecular targets

The pharmacological effects of berberine are based on its interactions with multiple molecular targets, mainly including:

IDO inhibitory effect

IDO (indoleamine 2,3-dioxygenase) is a key enzyme in tryptophan metabolism, involved in regulating immune escape. As a non competitive inhibitor, berberine reduces its catalytic activity by binding to the inactive sites of IDO, with a Ki value of 5.8 μ M and an IC50 of 6.3 μ M. This inhibitory effect helps restore the immune system's ability to recognize and eliminate tumor cells or infectious pathogens.

Antibacterial targets

• GYRA (DNA gyrase A)Huanglian alkaloids interfere with the supercoiled structure of bacterial DNA, blocking DNA replication and transcription processes.
• DHFR (dihydrofolate reductase)Inhibit bacterial folate metabolism, hinder nucleic acid and protein synthesis.
• GYPB、MECA、PENA Involved in bacterial cell wall synthesis and metabolism, berberine enhances its antibacterial effect through multi-target synergistic action.

Other mechanisms of action

Huanglian alkaloids also affect cellular signaling pathways such as NF - κ B and MAPK, regulate inflammatory responses and cell apoptosis, and promote the recovery of immune function in the body.

Evaluation of drug properties and pharmacokinetics

The pharmacological parameters of coptisine indicate that it has certain potential for drug development, but there are also several challenges.

Analysis of drug properties parameters

• Molecular weight (320.32)Complies with Lipinski's rules and is beneficial for oral absorption.
• LogP（0.10）Low fat solubility may affect cell membrane penetration, but is beneficial for water solubility and in vivo distribution.
• TPSA（64.88 Ų）Moderate polarity is beneficial for bioavailability.
• Number of hydrogen bond acceptors (5)Meets drug design requirements.
• Low permeability of blood-brain barrier Restricting the application of central nervous system diseases.
• Hepatotoxicity unknown Further safety evaluation is required.
• Cardiotoxicity and hERG inhibition positive There is a potential risk to the heart, and attention should be paid to heart safety.

Pharmacokinetic characteristics

At present, there is limited data on the in vivo absorption, distribution, metabolism, and excretion (ADME) of berberine. Previous studies have shown that:

• The oral absorption rate is moderate, and the bioavailability is limited by intestinal metabolism and first pass effects.
• Mainly metabolized through the liver, the metabolites have not been fully identified.
• The main excretion pathways are bile and urine.

In the future, systematic pharmacokinetic studies are needed to clarify the in vivo behavior and metabolic safety of berberine.

Clinical application prospects and prospects

Huanglian alkaloids have shown broad prospects in clinical applications due to their multi-target and multifunctional pharmacological properties.

Anti drug resistant bacterial infection

With the global threat of drug-resistant bacterial infections, the development of berberine as a novel antibacterial agent is of great significance. Its inhibitory effect on multiple drug-resistant bacterial targets provides a new approach for clinical anti infective treatment. In the future, its antibacterial activity and safety can be improved through structural optimization and drug combination strategies.

Tumor immunotherapy

IDO inhibitors have attracted much attention in tumor immunotherapy. Huanglian alkaloid, as a natural product IDO non competitive inhibitor, has the potential to regulate the immune microenvironment and is expected to be used in combination with immune checkpoint inhibitors to enhance anti-tumor effects.

Safety and Toxicology

The cardiac toxicity and hERG channel inhibition of berberine suggest that its clinical application should be cautious, and systematic toxicological evaluation and dose optimization must be carried out to ensure medication safety.

Future research directions

• Thoroughly analyze the molecular mechanism of action and target network of berberine.
• Optimize chemical structure, reduce cardiac toxicity, and enhance drug efficacy.
• Develop new drug delivery systems to improve bioavailability.
• Conduct preclinical and clinical trials to verify its safety and efficacy.

Conclusion

Huanglian alkaloid, as an isoquinoline alkaloid derived from the traditional Chinese medicine Huanglian, has shown significant research value in the fields of anti drug resistant bacterial infections and tumor immune regulation due to its unique chemical structure and diverse pharmacological activities. The discovery of it as a non competitive inhibitor of IDO provides a new natural drug candidate molecule for tumor immunotherapy. Meanwhile, the inhibitory effect of berberine on various bacterial targets gives it potential advantages in the development of antibacterial drugs.

However, the cardiac toxicity and pharmacokinetic properties of berberine still require further research and optimization. In the future, through structural modification, dosage form innovation, and systematic safety evaluation, berberine is expected to become an important component of the new generation of anti infective and immunomodulatory drugs. Overall, the study of berberine not only enriches the theoretical system of natural product pharmacology, but also provides valuable resources and insights for clinical drug development.