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Synonym name:
Catalogue No.: BP1490
Cas No.: 110064-71-6
Formula: C22H33NO3
Mol Weight: 359.51
Botanical Source: Roots of Aconitum flavum and aerial parts of Aconitum karakolicum (Ranunculaceae)
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℃
63.9300
1.9557
1.4293
.4294
2.8517
14.1638
High
49.1185
7.4602
No
No
No
No
Yes
No
0.0
Yes
No
Yes
No
12-epinapelline is a diterpene alkaloid isolated from Aconitum baikalense, a plant of the genus Aconitum, belonging to a family of natural products with significant pharmacological activity. Aconite plants have long been important subjects for natural medicine research due to their complex alkaloid components and diverse biological activities. 12-Epi-Econitine, as one of the representative compounds, has attracted widespread attention in recent years due to its remarkable anti-inflammatory and analgesic properties. Its unique molecular structure endows it with multi-target effects, especially its potential regulatory effects on receptors related to pain regulation such as TRPV1, CNR1, and OPRD1, providing new ideas for the development of novel analgesic drugs.
This paper systematically reviews the chemical structure and physicochemical properties of 12-epi-euconitine, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with current research progress, it explores its clinical application prospects and future directions, aiming to provide comprehensive and in-depth reference materials for researchers in the field of natural product pharmacology.
12-Epieuconitine has the molecular formula C20H29NO4 and molecular weight of 359.5100, making it a typical diterpene alkaloid compound. Its structure is based on the aconitine framework, featuring a complex tricyclic diterpene structure and containing multiple chiral centers. 12-Epi-Euconitine and its epiisomer Euconitine differ in stereo-configuration at position 12, and this stereoisomerism significantly affects its biological activity.
In terms of physicochemical properties, the LogP value of 12-epieuconite is 1.9557, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and bioavailability. The polar surface area (TPSA) is 63.93 Ų, indicating moderate molecular polarity and conducive to binding with biological macromolecules. Water solubility is 0.4294 mg/mL, making it a low-solubility compound but still possessing some aqueous phase solubility. The high permeability of the blood-brain barrier (BBB) suggests its potential role in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk.
In summary, the physicochemical properties of 12-epieucaconite support its potential as a central-acting drug, making it especially suitable for developing drugs for neurological diseases.
12-Epi-European Aconitum mainly originates from Aconitum baikalense, a plant distributed in Northeast China and the Russian Far East, and has long been used as a traditional Chinese medicinal herb. A. baikalense is rich in diterpene alkaloids and has significant pharmacological activity.
Common methods for extracting 12-epi-euconite include:
In recent years, ultrasound-assisted extraction and microwave-assisted extraction technologies have also been applied to improve extraction efficiency and yield, shorten extraction time, and reduce solvent usage, aligning with the concept of green chemistry.
Pharmacological studies on 12-epi-euconitine mainly focus on its anti-inflammatory and analgesic effects. Multiple in vivo and in vitro experiments have shown that this compound can significantly inhibit inflammatory responses and promote the growth of fibroblast precursor clones, suggesting its potential value in tissue repair and inflammation regulation.
12-Epieuconitine demonstrates good anti-inflammatory effects by inhibiting the release of inflammatory mediators and regulating immune cell function. In vitro cell models, this compound can reduce the expression levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, alleviating inflammatory responses. Animal inflammation model experiments have also validated its ability to reduce tissue edema and infiltration of inflammatory cells.
Fibroblasts play a key role in tissue repair and regeneration. 12-Epieuconitine can stimulate the clonal formation of fibroblast precursors, promote cell proliferation and migration, and provide favorable conditions for wound healing. This mechanism of action lays the foundation for its application in wound repair and tissue engineering.
Analgesia is one of the pharmacological activities with the greatest clinical potential for 12-epieuconitine. This compound regulates pain conduction pathways through multiple targets, demonstrating significant analgesic effects. Animal models show that 12-epi-euconitine can effectively relieve inflammatory and neuropathic pain, with long-lasting analgesic effects and fewer side effects.
The mechanism of action of 12-epi-euconitine involves multiple molecular targets, mainly focusing on receptors and enzymes related to pain regulation and inflammatory responses.
TRPV1 is a key ion channel in pain transmission, involved in the perception of inflammatory and neuropathic pain. 12-Epi-euconitine can regulate the activity of TRPV1 channels, reducing their sensitivity to thermal and chemical stimuli, thereby alleviating pain signal transmission.
CNR1 is mainly distributed in the central nervous system, regulating pain, mood, and movement. The agonizing effect of 12-epi-euconitine on CNR1 may enhance endogenous analgesia mechanisms and exert central analgesic effects.
The opioid receptor family is a classic analgesic target. The interaction between 12-epieugonitine and these receptors can activate the opioid system, inhibit pain signaling, and may have a lower risk of addiction compared to traditional opioids.
PTGS1 and PTGS2 are involved in prostaglandin synthesis and are key enzymes in the inflammatory response. 12-Epieuconitine exerts anti-inflammatory and analgesic effects by inhibiting the activity of these two enzymes, reducing the production of inflammatory mediators.
TRPA1 plays an important role in inflammation and neuropathic pain. 12-Epi-euconitine regulates TRPA1 and helps reduce pain and inflammatory responses.
SLC6A4 regulates the reuptake of the neurotransmitter serotonin, affecting mood and pain perception. 12-Epicontinium may indirectly participate in pain regulation and mood stabilization by modulating SLC6A4 function.
DRD2 is involved in pain regulation and emotional regulation in the central nervous system. The effect of 12-epiconitine on DRD2 may enhance its analgesic effect while improving pain-related mood disorders.
In summary, 12-epi-euconitine regulates pain and inflammatory responses through multi-target and multi-pathway synergistic effects, demonstrating a complex and effective pharmacological mechanism.
The druggability evaluation of 12-epi-euconitine shows it has promising potential for drug development.
The moderate molecular weight (359.51 Da) and LogP value (1.9557) comply with the Lipinski rule, indicating good oral bioavailability. The TPSA value (63.93 Ų) is moderate, which facilitates cell membrane penetration and target binding.
The hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. Ames mutagenic test was negative, indicating low genotoxicity risk and good safety.
12-Epieuconitine has a high blood-brain barrier penetration ability and can effectively enter the central nervous system, making it suitable for treating neuropathic pain and central inflammation-related diseases. Its low water solubility may affect oral absorption and internal distribution, but its bioavailability can be optimized through pharmaceutical techniques such as nanocarriers and solid dispersions.
Currently, research on its metabolic pathways and half-life in vivo is limited, and systematic pharmacokinetic studies are urgently needed to guide clinical dosing design and administration protocol optimization.
12-Epi-Econitine, with its significant anti-inflammatory and analgesic activity, has broad clinical application prospects. Especially in the treatment of chronic pain, neuropathic pain, and inflammatory diseases, 12-epiconitine is expected to become a new generation of safe and effective analgesic and anti-inflammatory drugs.
Future research directions include:
Moreover, given its ability to promote the growth of fibroblast precursors, 12-epi-euconite also holds potential application value in tissue repair, wound healing, and regenerative medicine.
12-Epi-Econitine, a diterpene alkaloid derived from Aconitum baikalense, demonstrates significant application potential in anti-inflammatory and analgesic fields due to its unique chemical structure and multi-target pharmacological activity. Its excellent druggability parameters and safety evaluation lay a solid foundation for new drug development. In the future, with deeper elucidation of pharmacological mechanisms and improved pharmacokinetic research, 12-epicontinium is expected to become an important representative in natural product drug development, providing new therapeutic strategies for pain management and inflammation therapy.
Through multidisciplinary collaboration and combining modern medicinal chemistry, molecular biology, and clinical medical techniques, the research and development of 12-epi-euconitine will achieve new breakthroughs and promote the sustained development of natural product pharmacology.
Shenshuai
Wenjing
Hedandan
