Synonym name:
Catalogue No.: BP0455
Cas No.: 70553-76-3
Formula: C₃₇H₄₂N₂O₆
Mol Weight: 610.751
Botanical Source: Alkaloid from Menispermum dauricum (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.

HNMR of Daurisoline

HPLC of Daurisoline

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

Introduction/Overview

Daurisoline, CAS number 70553-76-3, is a bibenzyl isoquinoline alkaloid derived from the traditional Chinese medicine Menispermum dauricum and its rhizome Rhizoma Menispermi. As an important natural product, bat gethulin has attracted widespread attention in recent years in cardiovascular disease and oncology research due to its unique chemical structure and multi-target pharmacological activity. In particular, its blocking effect on hERG pathways gives it antiarrhythmic potential, and as an effective autophagy blocker, it offers new ideas for cancer treatment.

This review aims to systematically summarize the chemical structure and physicochemical properties of bat gesulfurine alkaloids, plant origins and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its molecular targets in related diseases such as lung cancer, it explores its clinical application prospects and future research directions, providing references for researchers in natural product pharmacology and drug developers.

Chemical structure and physicochemical properties

Bat gesulin alkaloids belong to the bibenzyl isoquinoline alkaloids, with a molecular formula of C_37H_42N_2O_6 and a molecular weight of 610.75. Its structural core is formed by two isoquinoline units bridged by benzyl groups, featuring high molecular complexity and stereochemical characteristics. These structures endow them with strong biological activity and potential for binding to various targets.

In terms of physicochemical properties, the LogP value of bat gesuline is about 4.5, indicating good lipid solubility, which facilitates cell membrane penetration but may affect water solubility. The polar surface area (TPSA) is 84.34 Ų, and the number of hydrogen bond acceptors is 8, indicating that it possesses certain polarity and hydrogen bond formation capabilities in intermolecular interactions. Its blood-brain barrier penetration ability is weak, suggesting limited central nervous system exposure. There is a potential risk of cardiotoxicity, mainly due to its inhibitory effect on hERG potassium channels. Hepatotoxicity and genotoxicity (Ames test) are still unclear and require further research.

Plant Origins and Extraction Methods

Bat Gesulinine is mainly isolated from Menispermum dauricum and its dried rhizome, Rhizoma Menispermi. Bat pothos is a perennial woody vine widely distributed in Northeast China and the Korean Peninsula. In traditional Chinese medicine, it is used to promote blood circulation, remove blood stasis, relieve pain, and fight inflammation.

The extraction process typically uses alcohol solvents (such as ethanol or methanol) to extract dried plant material by reflux, followed by acid-base separation and liquid-liquid extraction to enrich alkaloid components. The purification process mostly uses column chromatography, including silica gel columns, C18 reversed-phase columns, and high-performance liquid chromatography (HPLC) separation, ultimately obtaining high-purity bat gesulin alkaloids.

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, while reducing solvent usage and extraction time, providing technical support for industrial production.

Pharmacological activity research

Antiarrhythmic effects

Bat gesulin alkaloid was first discovered to possess significant antiarrhythmic activity. It blocks hERG (human Ether-à-go-go-Related Gene) potassium channels in myocardial cells, regulates action potentials and stabilizes cardiac electrophysiology, thereby preventing arrhythmias. Multiple in vitro and in vivo experiments have confirmed its protective effect on arrhythmia models, especially showing good efficacy in atrial and ventricular arrhythmias.

However, blocking the hERG channel may also induce cardiotoxicity, especially QT interval prolongation and potential arrhythmic risks, posing safety challenges for its clinical application.

Antitumor activity and autophagy blocker

In recent years, research on bat gethulin alkaloid has gradually increased in the field of oncology, especially showing significant antitumor activity in lung cancer models. Its anticancer mechanism is closely related to its function as an autophagy blocker. Autophagy, as an important intracellular metabolic regulation and stress response process, plays a dual role in tumor cell survival and drug resistance. Bat gesulinine inhibits autophagy flow, blocks the protective mechanisms of tumor cells, enhances the sensitivity of chemotherapy drugs, and promotes tumor cell apoptosis.

In addition, bat gesulinine has regulatory effects on various tumor-related signaling pathways, including BCL2, STAT3, MAPK, and PI3K/Akt, demonstrating its multi-target synergistic anti-tumor potential.

Mechanism of action and molecular targets

The pharmacological effects of bat gesuline involve various molecular targets and signaling pathways, mainly including:

• hERG potassium channel: As an important current channel for myocardial cells, blocking hERG channels is a key mechanism for bat gethulin alkaloid to fight arrhythmias, but it also carries potential cardiotoxicity risks.

• Autophagy-related proteins: Bat gesulin blocks the autophagy protection mechanism of tumor cells by inhibiting autophagy streams, affecting the expression of autophagy markers such as LC3-II and p62.

• Lung cancer-related targets:

• BCL2: A key protein regulating cell apoptosis, bat gethulin alkaloid promotes tumor cell apoptosis by downregulating BCL2 expression.
• STAT3: Involved in tumor cell proliferation and immune escape, bat gethulin can inhibit STAT3 signaling pathway activity.
• ESR2 (estrogen receptor β): affects cell proliferation and differentiation; bat gesulinine may participate in anti-tumor effects by regulating its expression.
• MAPK1/MAPK8: Regulates cellular stress response and apoptosis; bat gestorinine modulates the MAPK signaling pathway to help suppress tumor growth.
• PIK3CG :P member of the I3K family and involved in cell survival and metabolism. Bat gesselinline may regulate tumor cell metabolic status through this target.
• RELA (NF-κB p65): A key transcription factor that regulates inflammation and the tumor microenvironment. Bat gesulin inhibits its activity and weakens the tumor pro-inflammatory environment.
• CASP9: A key enzyme in the endogenous apoptosis pathway, bat gethulin promotes tumor cell apoptosis by activating CASP9.
• PPARG: A nuclear receptor that regulates metabolism and cell differentiation. Bat-based gethulin may participate in anti-tumor processes by modulating PPARG.

In summary, bat gesulinine achieves its antiarrhythmic and antitumor pharmacological effects through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

Druggability parameters

The molecular weight of bat gethulin alkaloid is 610.75, and a higher molecular weight may affect the oral bioavailability of its drug. The LogP value is 4.5, indicating strong lipid solubility, which facilitates cell membrane penetration, but may result in insufficient water solubility, affecting distribution in vivo. TPSA is 84.34 Ų, which is in a moderate range and favors target binding.

The number of hydrogen bond receptors is 8, indicating strong hydrogen bonding in target binding, but may also affect its ability to pass through biofilms. Its lower blood-brain barrier penetration reduces the risk of central nervous system toxicity.

Pharmacokinetic characteristics

Currently, pharmacokinetic research on bat gesuline is relatively limited. Existing studies have shown that it has a certain degree of metabolic stability in vivo, but its specific absorption, distribution, metabolism, and excretion (ADME) characteristics still require further study. Given its hERG channel-blocking activity, cardiotoxicity assessment is an important direction for future pharmacokinetic research.

In addition, there is a lack of data on hepatotoxicity and genotoxicity, and further confirmation of their safety is needed through in vitro and in vivo toxicology tests.

Prospects and outlooks for clinical applications

As a natural product with multiple pharmacological activities, bat gethulin alkaloid has broad clinical application potential. Its antiarrhythmic effects provide a new candidate drug for cardiovascular disease treatment, especially in cases of resistance to traditional drugs or significant side effects, where bat gesulinine may become an effective alternative.

In the field of tumor treatment, bat gethulin alkaloid demonstrates good anti-lung cancer activity through autophagy blocking and multi-target regulation. Its combined use with existing chemotherapy drugs is expected to overcome tumor resistance and improve treatment outcomes. Moreover, its multiple regulation of lung cancer-related signaling pathways provides a theoretical foundation for precision treatment.

However, the cardiotoxicity risk and pharmacokinetic characteristics of bat gesulfurine are not yet fully understood, limiting its clinical transformation. Future research should focus on optimizing molecular structure to reduce the risk of hERG channel blockade, improving drug metabolic stability and bioavailability. At the same time, systematic toxicological evaluation and preclinical safety studies are key steps in its clinical development.

By integrating modern drug design technologies, such as computer-aided drug design (CADD), structural modification, and drug delivery system development, bat gethulin alkaloid is expected to become an important candidate for next-generation antiarrhythmic and antitumor drugs.

Conclusion

As a natural bibenzyl isoquinoline alkaloid, bat gesulin alkaloid, with its unique chemical structure and multi-target pharmacological activity, shows broad application prospects in cardiovascular diseases and tumor treatment. Its blocking effect on the hERG pathway gives it antiarrhythmic potential, while its function as an autophagy blocker provides new strategies for anti-tumor therapy.

Although its druggability and safety remain somewhat challenging, with deeper research in medicinal chemistry, pharmacology, and pharmacokinetics, bat gethulin alkaloid is expected to achieve clinical translation through structural optimization and formulation improvements. In the future, multidisciplinary collaborative research will make it an important model for natural product drug development, benefiting cardiovascular and oncology patients.