Synonym name:
Catalogue No.: BP3675
Cas No.: 26067-60-7
Formula: C₂₁H₂₃NO₄
Mol Weight: 353.418
Botanical Source:

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. Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

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

Introduction/Overview

Dihydropalmatine (abbreviated as DHP) is a natural alkaloid with significant pharmacological activity, first isolated from the traditional medicinal plant Berberis aristata. As a natural product with multi-target effects, dihydroparmatine demonstrates good pharmacological potential in analgesia, anxiolysis, and neuroprotection. In recent years, with in-depth research into its molecular mechanisms and pharmacokinetic properties, dihydropalmatine has gradually become a research hotspot in the fields of natural product pharmacology and new drug development. This paper will systematically review the chemical structure and physicochemical properties of dihydropalmatine, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide scientific basis and reference for subsequent research and clinical translation.

Chemical structure and physicochemical properties

The chemical name of dihydropalmatine is (specific IUPAC name omitted), molecular formula C21H25NO4, and molecular weight 353.4180. Its structure belongs to the flavonoid alkaloid class, featuring a typical tetracyclic isoquinoline backbone, containing multiple methoxy and hydroxyl substituents, which imparts unique physicochemical properties. Its LogP value is 4.7534, indicating strong lipid solubility and facilitating lipid membrane penetration, especially the blood-brain barrier (BBB). TPSA (topological pole surface area) is 40.1600, indicating moderate polarity and favorable for cell membrane penetration. Low water solubility (0.0060 mg/mL) suggests limited solubility in the aqueous phase, which may affect oral bioavailability. Notably, dihydropalmatine does not exhibit hERG channel inhibitory activity, suggesting a low risk of cardiotoxicity; The Ames test result was 0.9, indicating a low genotoxicity risk.

The chemical structure of dihydropalmatine is shown in the figure below (structural formula diagrams may be provided in the text):

(Structural formula diagram omitted)

The isoquiline ring and methoxy group in its structure form the key structural basis for its interactions with multiple targets, affecting its receptor binding affinity and pharmacodynamic properties.

Plant Origins and Extraction Methods

Dihydropalmatine is mainly derived from Berberis aristata (Indian barberry), a plant belonging to the Berberidaceae family, used in traditional medicine to treat various diseases. Besides Berberis species, some other flavonoid alkaloid-rich plants can also detect dihydropalmatine, but at lower levels.

Traditional extraction methods mostly use organic solvent extraction combined with column chromatography separation. The specific process includes:

1. Raw material processing: Collect plant roots and stems, dry and crush them.
2. Solvent extraction by extraction: methanol or ethanol is commonly used as extraction solvents, extracted under reflux conditions for several hours to fully dissolve the alkaloid components.
3. Liquid-liquid separation: The extract is layered with water and organic solvents to remove non-polar impurities.
4. Column chromatography purification: Separation and purification are performed using silica gel or C18 reversed phase columns, combined with thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) to monitor purity.
5. Crystallization or drying: Purified dihydropalmatine is obtained by crystallization or spray drying.

Modern extraction technologies such as ultrasound-assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography-mass spectrometry (HPLC-MS) have been applied to improve extraction efficiency and purity, shorten extraction time, and reduce solvent consumption.

Pharmacological activity research

The pharmacological activity of dihydroparmatine is mainly concentrated in the central nervous system, with particularly significant analgesic effects. Its analgesic effects have been validated in various animal models, including models of inflammatory pain, neuropathic pain, and postoperative pain. In addition, dihydroparmatine also exhibits anti-anxiety, antidepressant, and neuroprotective effects.

Analgesic effect

Dihydropalmatine exerts analgesic effects through multi-target regulation, involving various receptors and ion channels. Animal experiments have shown that dihydroparmatine can significantly reduce pain responses caused by thermal and mechanical stimuli, and compared to classic opioid analgesics, it has fewer side effects and better tolerability.

Anti-anxiety and antidepressant

Research shows that dihydrobamatine regulates the central dopamine system, improving anxiety and depression-like behaviors in animals. Its mechanism of action may be related to regulation of dopamine D2 receptor (DRD2) and the serotonin transporter (SLC6A4).

Neuroprotective effects

Dihydropalmatine demonstrates certain neuroprotective effects in neurodegenerative disease models, reducing oxidative stress and inflammatory responses, promoting nerve cell survival, and suggesting potential application value in diseases such as Parkinson's and Alzheimer's.

Mechanism of action and molecular targets

The pharmacological effects of dihydropalmatine depend on its interactions with multiple molecular targets, demonstrating the characteristic of multi-target and multi-pathway coordinated regulation.

1. TRPV1 and TRPA1

TRPV1 (transient receptor potential vanillic acid receptor 1) and TRPA1 are important ion channels for sensing pain and inflammation. Dihydropalmatine can inhibit the activation of TRPV1 and TRPA1, reducing calcium influx and thereby alleviating pain conduction and inflammatory responses.

2. Opioid receptors (OPRD1, OPRM1, OPRK1)

Dihydroparmatine modulates three opioid receptors: δ (OPRD1), μ (OPRM1), and κ (OPRK1), promoting the analgesic effects of endogenous opioid systems, enhancing analgesia, and reducing dependence and side effects of traditional opioids.

3. CNR1 (Cannabinoid Receptor 1)

CNR1 regulates pain, emotions, and memory in the central nervous system. Dihydropalmatine activates CNR1 to help with analgesic and anti-anxiety effects.

4. PTGS1 and PTGS2 (cyclooxygenase-1 and -2)

PTGS1 and PTGS2 are involved in prostaglandin synthesis and are important mediators of inflammation and pain. Dihydropalmatine exerts anti-inflammatory and analgesic effects by inhibiting the activity of these two enzymes, reducing the production of inflammatory mediators.

5. SLC6A4 (5-serotonin transporter)

Dihydropalmatine modulates SLC6A4, affects the reuptake of 5-hydroxystryptamine, improves neurotransmitter balance, and participates in antidepressant and anti-anxiety mechanisms.

6. DRD2 (Dopamine D2 receptor)

DRD2 plays an important role in motor control and emotional regulation. Dihydrobamatine exerts neuroprotective and psychoregulatory effects by modulating the DRD2 signaling pathway.

In summary, dihydropalmatine exhibits complex pharmacological characteristics through multi-target synergistic effects to regulate pain conduction, inflammatory response, and neurotransmitter balance.

Druggability evaluation and pharmacokinetics

Efficacy evaluation

The druggability parameters of dihydrobamatine indicate that it has promising potential for drug development. A LogP value of 4.75 indicates high lipophilusity, facilitating crossing of the blood-brain barrier and meeting the ideal characteristics of central-acting drugs. TPSA is 40.16, and low polarity helps cell membrane penetration. Low water solubility suggests the need to optimize dosage forms to improve bioavailability. hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. The Ames test result was close to 1, indicating a low genotoxicity risk.

Pharmacokinetic characteristics

Animal experiments showed that dihydroparmatine was rapidly absorbed orally, with a shorter peak plasma concentration (Cmax) peak and wide distribution, especially high concentrations in brain tissue, which aligns with central nervous system efficacy. Its metabolism is mainly through the hepatic cytochrome P450 enzyme system, and its metabolites are excreted by the kidneys. It has a moderate half-life and good internal stability. Dihydroparmatine has weak induction or inhibitory effects on liver enzymes, resulting in a lower risk of drug interactions.

However, due to poor water solubility, oral bioavailability is limited, requiring improvements through new dosage form technologies such as nanoformulations and solid dispersions. At the same time, long-term toxicology and safety evaluations still need further improvement.

Prospects and outlooks for clinical applications

Dihydropalmatine, as a natural alkaloid with multi-target effects, has broad clinical application potential. Its remarkable analgesic effect makes it a strong candidate for the treatment of chronic pain, neuropathic pain, and inflammatory pain. Compared to traditional opioid analgesics, dihydropalmatine has milder side effects and a lower risk of dependence, meeting the needs of modern analgesic development.

Moreover, its anti-anxiety, antidepressant, and neuroprotective effects offer new approaches for treating neuropsychiatric disorders, especially in adjunctive therapy for neurodegenerative diseases such as Parkinson's and Alzheimer's.

Future research should focus on the following aspects:

1. Clinical trial design and implementation: Systematically evaluate the safety, efficacy, and dosage range of dihydrobamatine to promote its clinical translation.
2. Dosage Form Optimization: Improves water solubility and oral bioavailability, enhancing clinical application convenience.
3. In-depth mechanism analysis: Using multi-omics technology to reveal its multi-target action network, guiding precise medication.
4. Combination drug studies: Exploring synergistic effects with existing analgesics and antidepressants to reduce single drug dosage and side effects.
5. Long-term safety evaluation: Systematic monitoring of potential toxicity and drug resistance to ensure clinical drug safety.

Conclusion

Dihydropalmatine, a natural alkaloid derived from Berberis aristata, shows broad application prospects in the fields of analgesic and neuropsychiatric diseases due to its unique chemical structure and multi-target pharmacological effects. Its good druggability parameters and low toxicity risk lay a solid foundation for new drug development. In the future, through in-depth pharmacological mechanism research, formulation optimization, and clinical validation, dihydropalmatine is expected to become a safe and effective new natural drug, offering new strategies and options for clinical pain management and neurological disease treatment.