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

Corynoxene (CAS number: 630-94-4) is a natural alkaloid isolated from Uncaria rhynchophylla, belonging to the indole alkaloid family. Gouteng, as a traditional Chinese medicinal herb, has always been used to treat hypertension, headaches, and neurological diseases. The research on its active ingredients has received widespread attention in recent years. Dehydrorhynchophylline has become a research hotspot in the field of natural product pharmacology due to its unique pharmacological activity, especially its potential in inhibiting the proliferation and analgesic effects of vascular smooth muscle cells (VSMCs). This article provides a systematic review of the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of dehydrorhynchophylline, aiming to provide theoretical basis and research direction for its new drug development and clinical application.

Chemical structure and physicochemical properties

The molecular formula of dehydrorhynchophylline is C23H26N2O4, with a molecular weight of 398.46, and it belongs to the complex indole alkaloids. Its structural features include a typical indole skeleton, containing multiple oxidizing groups and nitrogen atoms, and possessing strong polarity and hydrogen bond acceptor ability. In terms of physicochemical properties, the LogP value of dehydrorhynchophylline is 2.26, indicating its moderate lipid solubility, which is beneficial for penetrating cell membranes and the blood-brain barrier (BBB). Its topological polar surface area (TPSA) is 82.46 Å ², indicating that the molecule has a good balance in polar and non-polar environments and is suitable for oral absorption and central nervous system action. The number of hydrogen bond receptors is 6, indicating that it may form multi-point hydrogen bond interactions when binding to target proteins, enhancing binding affinity. The drug safety evaluation showed that dehydrorhynchophylline has no hepatotoxicity, cardiotoxicity, hERG channel inhibition, or mutagenicity (Ames test negative), providing preliminary assurance for its safety.

Plant sources and extraction methods

Dehydrogenine is mainly isolated from Uncaria rhynchophylla. Gouteng is a plant of the genus Gouteng in the family Rubiaceae, widely distributed in southern China and Southeast Asia. It is a commonly used medicinal herb in traditional Chinese medicine for clearing heat, calming the liver, relieving wind, and stopping spasms. Gouteng contains abundant indole alkaloids, among which dehydrorhynchophylline has a higher content.

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

1. Raw material pretreatment Dried and crushed hooked vine, screened for suitable particle size.
2. Solvent extraction Ethanol or methanol is used for reflux extraction, and the extraction time is generally 2-4 hours. Repeat the extraction 2-3 times to improve the recovery rate.
3. Crude extract concentration Concentrate the extract under reduced pressure to obtain the crude extract.
4. Separation and purification Using silica gel column chromatography or reverse phase high-performance liquid chromatography (RP-HPLC) technology, combined with gradient elution, to separate and purify dehydrorhynchophylline.
5. Structural Identification Confirm the structure of the compound through 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 dehydrorhynchophylline, aiming to improve extraction efficiency and purity, reduce solvent residue, and promote industrial production.

Pharmacological activity research

1. Inhibition of proliferation of vascular smooth muscle cells

Dehydrorhynchophylline, as an effective ERK1/ERK2 inhibitor during PDGF-BB (platelet-derived growth factor BB) - induced proliferation of vascular smooth muscle cells (VSMCs), has demonstrated its potential therapeutic value in vascular pathology. Abnormal proliferation of VSMCs is the key pathological process of atherosclerosis, vascular stenosis and vascular remodeling. In vitro experiments have shown that dehydrorhynchophylline can significantly inhibit PDGF-BB-induced ERK1/ERK2 phosphorylation levels, block downstream signaling pathways, and thus inhibit VSMC proliferation and migration.

2. Analgesic effect

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

3. Neuroprotective effect

The protective effects of crochet vine and its component dehydrocrochet alkaloid in neurological diseases are gradually being studied. It exhibits potential protective effects against neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease by inhibiting neuroinflammation, regulating neurotransmitter balance, and antioxidant stress. Related in vitro and in vivo studies have confirmed that dehydrocrocetine can reduce neuronal apoptosis and improve cognitive function, indicating its potential application in the field of neuroprotection.

Mechanism of action and molecular targets

The pharmacological effects of dehydrorhynchophylline depend on its ability to regulate multiple signaling pathways and molecular targets.

1. Inhibition of ERK1/ERK2 signaling pathway

The phosphorylation of ERK1/ERK2 induced by PDGF-BB is a crucial step in VSMC proliferation. Dihydrorhynchophylline directly or indirectly inhibits the activation of ERK1/ERK2, blocks cell cycle progression, and suppresses cell proliferation and migration. This mechanism provides a molecular basis for its application in vascular lesions.

2. TRP channel adjustment

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

3. Regulation of opioid receptors and dopamine receptors

Dihydrorhynchophylline has a certain affinity for opioid receptors such as OPRM1, OPRD1, OPRK1, as well as DRD2 dopamine receptors. It may exert analgesic and psychomodulatory effects by regulating the release of neurotransmitters in the central nervous system.

4. Inhibition of cyclooxygenase

PTGS1 (COX-1) and PTGS2 (COX-2) are key enzymes in the inflammatory response, and the inhibitory effect of dehydrocrocetine on them helps alleviate inflammation related pain and tissue damage.

5. Penetration of blood-brain barrier

Dehydrorhynchophylline has high blood-brain barrier permeability and can effectively enter the central nervous system, exerting neuroprotective and analgesic effects, which is different from many peripheral analgesic drugs.

Evaluation of drug properties and pharmacokinetics

The pharmacological parameters of dehydrorhynchophylline show that it has good potential for drug development.

• Molecular weight (398.46)Moderate, in line with Lipinski's rules, beneficial for oral absorption.
• LogP（2.26）This indicates that its lipophilicity is moderate, which is conducive to cell membrane penetration and central nervous system distribution.
• TPSA（82.46 Ų）Within the range suitable for oral bioavailability and blood-brain barrier penetration.
• Number of hydrogen bond acceptors (6)Moderate, helps to form stable binding with the target.
• safety indicator: No hepatotoxicity, no cardiotoxicity, no hERG channel inhibition, and Ames test negative, indicating good safety.

In terms of pharmacokinetics, existing studies have shown that dehydrocrocetine is rapidly absorbed after oral administration, with a moderate plasma half-life, and can effectively distribute in brain tissue, suggesting its suitability for development as a central nervous system drug. Its metabolic pathway is mainly through the liver enzyme system, with low toxicity of metabolites and no significant cumulative effect observed.

Clinical application prospects and prospects

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

1. cardiovascular disease By inhibiting the abnormal proliferation of VSMCs, dehydroguncarine is expected to be used to prevent atherosclerosis, vascular remodeling and hypertension related vascular diseases.
2. Analgesic treatment Its regulatory effect on multiple pain related targets provides a new treatment strategy for chronic pain, neuropathic pain, and other intractable pain, especially suitable for central pain management.
3. neuroprotection In neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, dehydrocrocetine has shown anti-inflammatory, antioxidant, and neuroprotective effects, and can be used as an adjuvant therapy drug in the future.
4. Security advantage Its low toxicity and good pharmacological properties provide favorable conditions for clinical development.

Future research should focus on preclinical pharmacokinetic optimization, formulation development, and large-scale clinical trial validation of dehydrorhynchophylline. In addition, in-depth analysis of its molecular mechanism of action and target network will help to accurately locate its indications and promote it as a new generation of natural medicine.

Conclusion

Dehydrorhynchophylline, as an important active ingredient in Houttuynia cordata, has shown broad application prospects in cardiovascular disease, analgesia, and neuroprotection due to its unique chemical structure and multi-target pharmacological activity. Its good pharmaceutical properties and safety further support its value as a candidate molecule for natural medicine. In the future, interdisciplinary research combining modern medicinal chemistry, molecular biology, and clinical pharmacology will accelerate the drug development process of dehydrorhynchophylline and provide new solutions for the treatment of related diseases.