Synonym name:
Catalogue No.: BP0404
Cas No.: 25127-29-1
Formula: C₂₀H₂₁NO₄
Mol Weight: 339.391
Botanical Source: Alkaloid from Stephania capitata, Stephania sasakii and Stephania venosa (Menispermaceae)

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 Crebanine

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

Introduction/Overview

Crebanine, CAS number 25127-29-1, is an isoquinoline alkaloid derived from plants of the genus Stephania. As an important member of the natural product, kebanin has attracted widespread attention in pharmacology due to its multi-target and multi-pathway bioactivity. In recent years, Kebanin has demonstrated significant pharmacological potential in anti-tumor, neuroprotection, anti-inflammatory, and antibacterial properties, especially in research on hepatocellular carcinoma (HCC) and cerebral ischemia-related diseases. Its characteristics as an α7-nicotinic acetylcholine receptor (α7-nAChR) antagonist provide a theoretical foundation for further elucidating its mechanism of action and developing novel therapeutic drugs.

This paper will systematically review the chemical structure and physicochemical properties of Kebanin, its plant origins and extraction methods, with a focus on evaluating its pharmacological activity and mechanism of action, conducting a comprehensive evaluation combined with druggability parameters, and finally looking ahead to its clinical application prospects, aiming to provide reference for natural product pharmacology and new drug development.

Chemical structure and physicochemical properties

Kebanin belongs to the isoquinoline alkaloids, with a molecular formula of C_20H_23NO_4 and a molecular weight of 339.39. Its structure contains a typical isoquinoline backbone, with multiple oxygen functional groups and nitrogen atoms, providing a chemical basis for its interactions with various biological targets. Kebanin's LogP value is about 3.0, indicating moderate lipid solubility, which facilitates penetration of cell membranes and the blood-brain barrier (BBB), which is especially important for its neuroprotective effects. Its topological pole surface area (TPSA) is 55.82 Ų, and it has 5 hydrogen bond receptors, both within the ideal range for drug molecules to penetrate cell membranes.

From a physicochemical perspective, Kebanin is structurally stable, with a certain balance of water and lipid solubility, making it suitable for oral and injectable administration. Its high blood-brain barrier penetration capability supports its potential application in central nervous system diseases. Currently, safety indicators such as hepatotoxicity, cardiotoxicity, and hERG channel inhibition remain unclear, and further systematic research is needed.

Plant Origins and Extraction Methods

Kebanin is mainly isolated from plants of the genus Stephania. Stephania plants are widely distributed throughout tropical and subtropical Asia, and have traditionally been used in traditional medicine to treat inflammation, pain, and tumors. Kebanin, as one of the main alkaloids of this genus, has its content and distribution significantly influenced by plant species, growing environment, and harvest period.

The extraction method typically uses organic solvent extraction combined with column chromatography separation technology. The general steps include: crushing the dried Stephania plant material, refluxing extraction with methanol or ethanol, and enriching the alkaloid through acid-base adjustment after concentrating the extract. Subsequently, silica gel columns or C18 reversed phase columns were used for separation and purification, combined with high-performance liquid chromatography (HPLC) for monitoring purity. In recent years, the application of ultrasound-assisted extraction and supercritical fluid extraction technologies has improved the extraction efficiency and purity of kepanin, laying the foundation for its large-scale preparation.

Pharmacological activity research

Antitumor activity

Kebanin demonstrated significant anti-proliferation, migration inhibition, and invasion abilities across various cancer cell models. Its inhibitory effect on hepatocellular carcinoma (HCC) cell lines is particularly remarkable, capable of inducing apoptosis and blocking the cell cycle progression. Mechanistic studies have shown that Kebanin disrupts intracellular redox balance by triggering reactive oxygen species (ROS) bursts, thereby promoting the activation of apoptosis-related signaling pathways.

In addition, Kebanin regulates breast cancer-related targets such as AMPK, BCL2, STAT3, ESR2, ABCB1, ABCG2, PRKCA, MAPT, NFE2L2, and TOP1, demonstrating its multi-target action characteristics. By inhibiting tumor cell resistance mechanisms (such as ABCB1 and ABCG2-mediated drug efflux), kebanin holds promise as a potential drug for adjuvant chemotherapy.

Neuroprotective effects

Kebanin, as an α7-nAChR antagonist (IC50 19.1 μM), demonstrates good neuroprotective effects in neurological diseases. It can reduce excessive activation of NOX2 in microglia, lower ROS and peroxidation reactions, and exhibit significant antioxidant properties. Animal model studies have shown that Kebanin can effectively improve cerebral ischemia-reperfusion injury in rats with middle cerebral artery occlusive reperfusion (MCAO/R), reducing nerve cell damage.

Additionally, Kebanin significantly improved cognitive impairment in Scopolamine-induced ICR mice, suggesting its potential application value in Alzheimer's disease and other cognitive impairment disorders. This role may be closely related to its regulation of NF-κB, MAPK, and AKT/FoxO3a signaling pathways.

Antibacterial activity

Kebanin exhibits high inhibitory activity against Gram-positive animal pathogens, demonstrating its potential as a natural antimicrobial. Its mechanism of action is not yet fully understood, but it is speculated that it may involve disruption of bacterial cell membranes or inhibition of key enzyme activity. In the future, combined with structural optimization, new antibacterial drugs are expected to be developed.

Electrophysiological effects of the heart

Kebanin can inhibit voltage-dependent sodium currents in ventricular muscle cells in guinea pigs, suggesting its regulatory effect on cardiac electrophysiology. This characteristic may offer new ideas for treating diseases such as arrhythmias, but it also suggests that its cardiac safety requires further evaluation.

Mechanism of action and molecular targets

The multi-target mechanism of Kebanin mainly involves the following aspects:

1. α7-nAChR antagonist effect
   As an antagonist of α7-nAChR, Kebanin can regulate neurotransmitter release and inflammatory responses, reducing nervous system damage. α7-nAChR plays key roles in cognitive function, inflammation regulation, and the tumor microenvironment. The antagonistic effect of kebanin provides a foundation for its neuroprotective and antitumor effects.

2. ROS-mediated apoptosis
   Kebanin induces reactive oxygen species to burst, disrupting intracellular redox balance, activating mitochondrial pathways and apoptosis-related protein expression, and promoting cancer cell apoptosis. ROS accumulation simultaneously inhibits tumor cell migration and invasion capabilities.

3. Signal path regulation

4. AKT/FoxO3a pathway: Kebanin inhibits AKT activation, promotes FoxO3a nuclear translocation, and induces expression of apoptotic genes.
5. NF-κB pathway: Kebanin inhibits NF-κB activation, reducing inflammatory responses and tumor cell survival signals.

6. MAPK pathway: By regulating MAPK members such as ERK, JNK, and p38, kebanin controls the balance of cell proliferation and apoptosis.

7. NOX2 inhibition and antioxidant properties
   Kebanin exerts antioxidant and neuroprotective effects by inhibiting the overactivation of NOX2 in microglia, reducing ROS production.

8. Cardiac sodium current suppression
   Kebanin inhibits voltage-dependent sodium channels, affects action potentials in myocardial cells, suggesting its potential role in cardiac electrophysiological regulation.

9. Multi-target anti-tumor mechanism
   Kebanin regulates various breast cancer-related targets, including drug efflux pumps ABCB1 and ABCG2, anti-apoptotic protein BCL2, and signal transduction factor STAT3, comprehensively exerting anti-tumor effects.

Druggability evaluation and pharmacokinetics

Kebanin's molecular weight (339.39) and LogP (3.0) comply with the Lipinski rule, demonstrating good oral bioavailability potential. Its TPSA is 55.82 Ų, with 5 hydrogen bond receptors, both facilitating cell membrane penetration and blood-brain barrier crossing, supporting its application in central nervous system diseases.

Currently, safety data on kebanin's hepatotoxicity, cardiotoxicity, and hERG channel inhibition are still lacking and require systematic toxicological evaluation. High blood-brain barrier penetration may indicate possible central nervous system side effects, requiring close attention to dosage and safety window.

Pharmacokinetic research is still in its early stages. In the future, it is necessary to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, especially the interactions of metabolic enzymes and their in vivo half-life, to provide a basis for clinical formulation design.

Prospects and outlooks for clinical applications

With its multi-target and multi-pathway pharmacological activity, Kebanin shows broad application prospects in major diseases such as hepatocellular carcinoma, breast cancer, and cerebral ischemia. As an α7-nAChR antagonist and ROS regulator, it offers new approaches for the treatment of neurodegenerative diseases and tumors. Combined with its antibacterial and cardiac electrophysiological regulatory effects, Kebanin is expected to become a candidate molecule for multifunctional drug development.

Future research should focus on:

• Systematic toxicological and safety evaluations to clarify clinical application risks.
• In-depth research on pharmacokinetics and pharmacodynamics, optimizing dosage forms and administration regimens.
• Structural modification and drug design enhance activity and selectivity, reducing side effects.
• Preclinical and clinical trials validate its therapeutic effects, advancing translational medicine.
• Explore its combined application with existing drugs to achieve synergistic effects.

Conclusion

Kebanin, as a natural isoquinoline alkaloid with rich pharmacological activity, demonstrates significant value in anti-tumor, neuroprotection, and antibacterial fields thanks to its multi-target regulatory capabilities. Its unique mechanism of action and favorable druggability parameters provide a solid foundation for new drug development. Although its safety and pharmacokinetic data are still incomplete, with further research, Kebanin is expected to become an important breakthrough in the development of natural products, bringing new hope for the treatment of related diseases. Future research needs to strengthen mechanism analysis, optimize structure, and clinical translation, driving Kebanin to the forefront of clinical application.