Synonym name: Corynoxine A
Catalogue No.: BP0400
Cas No.: 6877-32-3
Formula: C₂₂H₂₈N₂O₄
Mol Weight: 384.476
Botanical Source: Alkaloid from Pseudocinchona africana, Uncaria macrophylla and Mitragyna speciosa (Rubiaceae, Naucleaceae)

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 Corynoxine

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

Introduction/Overview

Corynoxine (CAS No.: 6877-32-3) is a tetracyclic hydroxyindole alkaloid isolated from Uncaria rhynchophylla, and has attracted significant attention in recent years due to its unique pharmacological activity. As a natural autophagy enhancer, Knoruxine regulates intracellular autophagy pathways, especially by inhibiting the Akt/mTOR signaling axis, promoting the clearance of α-synuclein proteins, demonstrating potential application value in the treatment of neurodegenerative diseases and tumors. Liver cancer, as a malignant tumor with high incidence and mortality worldwide, involves complex regulation of multiple signaling pathways and molecular targets. Corucin demonstrates therapeutic potential in regulating related targets such as BCL2, STAT3, PIK3CA, and AKT1. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Kornuxine, aiming to provide theoretical basis and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

Conoxine belongs to the tetracyclic hydroxyindole alkaloid, with the molecular formula C22H26N2O4 and a molecular weight of 384.47. Its structural core is a typical indole alkaloid backbone, containing multiple hydroxyl and nitrogen atoms, giving it strong biological activity and high polarity. The LogP value of Coroxine is about 2.5, indicating moderate lipophilic properties, which facilitate membrane penetration without excessive lipophilusis and thus affecting bioavailability. The topological polar surface area (TPSA) is 87.01 Ų, suggesting that it may bind to biological macromolecules through certain polar interactions. The molecule contains six hydrogen bond receptors, providing a variety of binding sites for binding to target proteins. The lower permeability of the blood-brain barrier indicates limited distribution in the central nervous system, but this may also reduce the risk of central side effects. Currently, there is no clear data on the hepatotoxicity, cardiotoxicity, or hERG channel inhibition of Knoruxine, and further systematic toxicological evaluation is needed.

Plant Origins and Extraction Methods

Cornoxin mainly originates from Uncaria rhynchophylla, a commonly used traditional Chinese medicinal herb in the Rubiaceae family, and is widely distributed in southern China and Southeast Asia. Traditionally, Gouteng has been used to treat hypertension, headaches, and neurological disorders. Its active ingredients include various alkaloids, with Conoxine being one of the important indole alkaloids.

Kronocine is usually extracted using the alcohol extraction method. Fresh or dried Uncaria stems and leaves are crushed, then refluxed extraction using ethanol or methanol as solvent. The extract is purified through multiple steps including concentration, segregation, and column chromatography, ultimately obtaining high-purity konoxine. In recent years, the application of new technologies such as ultrasound-assisted extraction and microwave-assisted extraction has improved extraction efficiency and purity. Additionally, high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS) technology enables rapid qualitative and quantitative analysis of Kornuxin, providing technical assurance for its quality control.

Pharmacological activity research

Research on the pharmacological activity of Kornusin mainly focuses on its autophagy regulatory effect and antitumor potential. Numerous in vitro cell experiments and some animal model studies have shown that Konosin can significantly enhance autophagy levels and promote the degradation of abnormal proteins, especially its remarkable clearance of α-synuclein proteins. This mechanism is of great significance for neurodegenerative diseases such as Parkinson's disease.

In the field of oncology, Coroxin demonstrates anti-liver cancer activity through multi-target regulation. It can inhibit the proliferation, migration, and invasion of liver cancer cells, induce apoptosis, and its related mechanisms involve regulating key molecules such as the BCL2 family proteins, the STAT3 signaling pathway, and the PI3K/Akt/mTOR axis. In addition, Konusin also has certain regulatory effects on tumor-related targets such as TOP1, TERT, MMP9, EGFR, TP53, and NFKB1, suggesting that it may exert anti-tumor effects through multi-target synergistic effects.

Mechanism of action and molecular targets

The core mechanism of conucine's action mainly revolves around autophagy regulation and signaling pathway regulation. By inhibiting Akt kinase activity, it downregulates the mTOR signaling pathway, lifting the inhibition of autophagy and promoting the formation and function of the autophagosome. This mechanism not only helps eliminate abnormal proteins and damage organelles within cells, but also regulates cellular metabolic status and survival signals.

Regarding targets related to liver cancer treatment, Coroxin demonstrates multiple regulatory capabilities:

• BCL2: Conoxine downregulates the expression of the anti-apoptotic protein BCL2, promoting tumor cell apoptosis.
• STAT3: Inhibits phosphorylation of STAT3, blocks its transcriptional activity, and suppresses tumor cell proliferation and immune evasion.
• PIK3CA/AKT1: Interferes with the PI3K/Akt signaling pathway, inhibiting cell survival and proliferation signals.
• MMP9: Reduces the expression of matrix metalloproteinase MMP9, inhibiting tumor cell invasion and metastasis.
• EGFR: Regulates epidermal growth factor receptor signaling, affecting cell growth and differentiation.
• TP53: May promote cell cycle arrest and apoptosis by modulating the p53 pathway.
• NFKB1: Inhibits NF-κB signaling, reduces inflammatory response, and supports the tumor microenvironment.

Additionally, the effects of Coroxine on TOP1 (topoisomerase I) and TERT (telomerase reverse transcriptase) suggest that it may be involved in DNA repair and telomere maintenance mechanisms, further influencing tumor cell survival and proliferation.

Druggability evaluation and pharmacokinetics

The druggability parameters of Coroxin indicate that it has certain potential for drug development. Moderate molecular weight (384.47) and LogP (2.5) comply with the Lipinski rule, facilitating oral absorption and cell membrane penetration. TPSA is 87.01 Ų, indicating moderate polarity and possibly good bioavailability. However, Konusin has relatively low blood-brain barrier permeability, limiting its application in central nervous system diseases, but may reduce central side effects in peripheral targeted therapy.

Currently, safety data on Knoruxine's hepatotoxicity, cardiotoxicity, and hERG channel inhibition are lacking, and systematic in vitro toxicological studies are urgently needed. Additionally, the pharmacokinetic characteristics of conucine, such as absorption, distribution, metabolism, and excretion (ADME), have not been fully elucidated. Preliminary hypothesis suggests that its metabolism may involve hepatic enzyme systems, and due to its alkaloid nature, there may be a certain first-pass effect. In the future, in vivo pharmacokinetic studies are needed to clarify its half-life, bioavailability, and metabolites, providing a basis for clinical formulation design.

Prospects and outlooks for clinical applications

As a natural autophagy enhancer, Coroxine has shown unique advantages in treating neurodegenerative diseases such as Parkinson's and Alzheimer's, especially by promoting the clearance of α-synuclein and slowing down the process of nerve damage. Although its blood-brain barrier permeability is limited, structural modification or nanocarrier delivery technology is expected to enhance the bioavailability of the central nervous system.

In the field of cancer treatment, Coroxine targets multiple signaling pathways and molecular targets related to liver cancer, demonstrating synergistic anti-tumor activity across multiple targets and showing potential as an adjunctive therapy for liver cancer. By combining modern medicinal chemistry and pharmacological approaches, Coroxine can serve as a lead compound for structural optimization, enhancing its targeting and efficacy while reducing potential toxicity.

Future research should focus on:

1. Systematically evaluate the safety and toxicological characteristics of Coroxin to clarify the risk-benefit ratio of its clinical application.
2. In-depth analysis of its molecular mechanisms, especially regulatory networks within the liver cancer microenvironment.
3. Develop efficient drug delivery systems to improve in vivo stability and targeted delivery capabilities.
4. Design and conduct preclinical and clinical trials to verify treatment efficacy and safety.

Conclusion

As a natural tetracyclic hydroxyindole alkaloid derived from Gou Teng, Conoxine shows broad prospects for drug development thanks to its remarkable autophagy-enhancing activity and multi-target antitumor effects. Although current toxicological and pharmacokinetic research is insufficient, its unique mechanism of action and favorable druggability parameters lay a solid foundation for subsequent drug optimization and clinical translation. In the future, through multidisciplinary collaboration, Corroxin is expected to become a new natural drug for treating major diseases such as neurodegenerative diseases and liver cancer, providing new therapeutic strategies for clinical practice.