Synonym name:
Catalogue No.: BP0399
Cas No.: 630-94-4
Formula: C₂₂H₂₆N₂O₄
Mol Weight: 382.46
Botanical Source: Alkaloid from Pseudocinchona africana (preferred genus name Corynanthe), Mitragyna rotundifolia, Mitragyna speciosa and Uncaria attenuata (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.

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

Introduction/Overview

Corynoxeine (CAS No.: 630-94-4) is a natural alkaloid isolated from Uncaria rhynchophylla, belonging to the indole alkaloid family. As a traditional Chinese medicinal herb, Uncaria has long been used to treat hypertension, headaches, and neurological disorders, and research on its active components has received widespread attention in recent years. Dehydroarticapitine has become a research hotspot in the field of natural product pharmacology due to its unique pharmacological activity, especially its potential to inhibit vascular smooth muscle cell (VSMCs) proliferation and analgesic effects. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of dehydrounutenoidine, aiming to provide a theoretical basis and research direction for its new drug development and clinical application.

Chemical structure and physicochemical properties

Dehydrounuterine has a molecular formula of C23H26N2O4 and a molecular weight of 398.46, making it a complex indole alkaloid. Its structural features include a typical indole framework containing multiple oxide groups and nitrogen atoms, with strong polarity and hydrogen bond acceptor capabilities. In terms of physicochemical properties, Dehydroglycolypine has a LogP value of 2.26, indicating moderate lipid solubility, which helps cross cell membranes and the blood-brain barrier (BBB). Its topological pole surface area (TPSA) is 82.46 Ų, indicating that the molecule maintains good balance in polar and nonpolar environments, making it suitable for oral absorption and central nervous system function. There are 6 hydrogen bond receptors, suggesting that they may form multi-point hydrogen bonds when binding to target proteins, enhancing binding affinity. Safety evaluation of the drug showed that dehydromethrine had no hepatotoxicity, cardiotoxicity, hERG channel inhibition, or mutagenicity (Ames test was negative), providing preliminary safety assurance.

Plant Origins and Extraction Methods

Dehydrouncaria rhynchophyllaine is mainly isolated from Uncaria rhynchophylla. Gouteng belongs to the Rubiaceae family and the genus Gouteng, widely distributed in southern China and Southeast Asia. It is a commonly used traditional Chinese medicine for clearing heat, calming the liver, calming wind, and relieving spasms. Uncaria contains abundant indole alkaloids, with dehydrodecanutenine being relatively high.

The extraction process typically uses organic solvent extraction combined with column chromatography for separation. The specific steps include:

1. Raw material pretreatment: Uncaria is dried and crushed, then selected for suitable particle size.
2. Solvent extraction by reflux: Ethanol or methanol is used for reflux extraction, usually taking 2-4 hours, with extraction repeated 2-3 times to improve recovery rate.
3. Crude extract concentration: The extract is concentrated under reduced pressure to obtain the crude extract.
4. Separation and purification: Using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC) technology, combined with gradient elution, dehydrogenated cocotomine is separated and purified.
5. Structural identification: Confirm compound structure using modern analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).

In recent years, supercritical fluid extraction and membrane separation technologies have also been attempted to be applied to the extraction of dehydrocotodecine, aiming to improve extraction efficiency and purity, reduce solvent residues, and promote industrial production.

Pharmacological activity research

1. Inhibition of vascular smooth muscle cell proliferation

Dehydrounatel-Glutostanine, as an effective ERK1/ERK2 inhibitor in the proliferation of vascular smooth muscle cells (VSMCs) induced by PDGF-BB (platelet-derived growth factor-BB), demonstrates its potential therapeutic value in vascular pathological conditions. Abnormal proliferation of VSMCs is a key pathological process in atherosclerosis, vascular stenosis, and vascular remodeling. In vitro experiments showed that dehydrochotenyline significantly inhibited the phosphorylation levels of ERK1/ERK2 induced by PDGF-BB, blocking their downstream signaling pathways and thereby suppressing the proliferation and migration of VSMCs.

2. Analgesic effect

Research on dehydroanticodotine in the field of analgesia suggests it may act through a multi-target mechanism. Relevant targets include TRPV1, CNR1, OPRD1, PTGS1, TRPA1, PTGS2, SLC6A4, OPRM1, OPRK1, and DRD2, all of which are involved in pain transmission and regulation. Dehydroartiptoline may alleviate chronic pain, neuropathic pain, and inflammatory pain by modulating the function of these targets. Animal model studies have shown that dehydromethrine can significantly reduce pain responses caused by thermal and mechanical stimuli, demonstrating good analgesic effects.

3. Neuroprotective effects

The protective effects of uncaria and its component dehydrounateline in neurological diseases are gradually gaining attention. By inhibiting neuroinflammation, regulating neurotransmitter balance, and antioxidant stress, it demonstrates potential protective effects against neurodegenerative diseases such as Parkinson's and Alzheimer's. Relevant in vitro and in vivo studies have confirmed that dehydrouncterygine can reduce neuronal apoptosis and improve cognitive function, suggesting its promising application in neuroprotection.

Mechanism of action and molecular targets

The pharmacological effects of dehydrounctum depend on its regulatory ability to control multiple signaling pathways and molecular targets.

1. Suppression of ERK1/ERK2 signaling pathways

PDGF-BB-induced ERK1/ERK2 phosphorylation is a key step in VSMC proliferation. Dehydrounatelium inhibits the activation of ERK1/ERK2 directly or indirectly, blocking the cell cycle and suppressing cell proliferation and migration. This mechanism provides the molecular basis for its application in vascular lesions.

2. TRP channel adjustment

TRPV1 and TRPA1 are important ion channels for sensing pain and inflammation. Dehydrounutenine can regulate the activity of these channels, reduce the excitability of nerve endings, and lessen the transmission of pain signals.

3. Regulation of opioid and dopamine receptors

Dehydrounctateline has certain affinity for opioid receptors such as OPRM1, OPRD1, OPRK1, and DRD2 dopamine receptors, and may exert analgesic and psychomodulatory effects by regulating neurotransmitter release in the central nervous system.

4. Cyclooxygenase inhibition

PTGS1 (COX-1) and PTGS2 (COX-2) are key enzymes in the inflammatory response, and dehydrounctoline inhibits them to help alleviate inflammation-related pain and tissue damage.

5. Blood-brain barrier penetration

Dehydrounateline has high blood-brain barrier permeability, allowing it to effectively enter the central nervous system and exert neuroprotective and analgesic effects, distinguishing it from many peripheral analgesic drugs.

Druggability evaluation and pharmacokinetics

The druggability parameters of dehydrounctoline indicate that it has promising potential for drug development.

• The molecular weight (398.46) is moderate, complies with the Lipinski rule, and is beneficial for oral absorption.
• LogP(2.26) indicates moderate lipid solubility, which facilitates cell membrane penetration and central nervous system distribution.
• TPSA (82.46 Ų) falls within the range suitable for oral bioavailability and blood-brain barrier penetration.
• The number of hydrogen bond receptors (6) is moderate, which helps form stable binding to the target.
• Safety indicators: No hepatotoxicity, no cardiotoxicity, no hERG channel inhibition, and Ames test negative, indicating good safety.

In terms of pharmacokinetics, existing studies show that dehydrounquitetine is rapidly absorbed orally and has a moderate plasma half-life, allowing effective distribution in brain tissue, suggesting its suitability for development as a central nervous system drug. Its metabolic pathway mainly involves hepatic enzyme systems, with low toxicity of metabolites and no significant cumulative effects.

Prospects and outlooks for clinical applications

Dehydrohookotaline, as a natural product with multiple targets and multiple mechanisms, has broad clinical application potential:

1. Cardiovascular diseases: By inhibiting abnormal proliferation of VSMCs, dehydrounutentine is expected to be used to prevent and treat atherosclerosis, vascular remodeling, and hypertension-related vascular lesions.
2. Analgesia therapy: Its regulatory effect on various pain-related targets provides new treatment strategies for chronic pain, neuropathic pain, and other refractory pains, especially suitable for central pain management.
3. Neuroprotection: In neurodegenerative diseases such as Parkinson's and Alzheimer's, dehydrountobutezine demonstrates anti-inflammatory, antioxidant, and neuroprotective effects, and may serve as an adjunctive therapy in the future.
4. Safety advantages: Its low toxicity and good druggability provide favorable conditions for clinical development.

Future research should focus on preclinical pharmacokinetic optimization, formulation development, and large-scale clinical trial validation of dehydrounutenaline. In addition, in-depth analysis of its molecular mechanisms and target networks will help accurately identify its indications and promote it as a new generation of natural medicines.

Conclusion

Dehydrounctum sine, as an important active ingredient in uncaria, demonstrates broad application prospects in cardiovascular diseases, analgesia, and neuroprotection due to its unique chemical structure and multi-target pharmacological activity. Its excellent druggability and safety further support its value as a natural drug candidate. In the future, multidisciplinary research combining modern medicinal chemistry, molecular biology, and clinical pharmacology will accelerate the drug development process for dehydrounctate, providing new solutions for the treatment of related diseases.