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Synonym name:
Catalogue No.: BP0763
Cas No.: 4491-19-4
Formula: C34H47NO10
Mol Weight: 629.747
Botanical Source: Alkaloid from roots of Aconitum chasmanthum, Aconitum ferox, Aconitum falconeri, Aconitum franchetti and Aconitum violaceum (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.
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℃
133.2200
2.3740
2.2666
.1245
1.9684
6.8801
Low
72.6086
7.1784
No
No
Yes
No
No
No
0.6
Yes
No
Yes
Yes
Indaconitine is a natural alkaloid isolated from Aconitum plants and belongs to the dihydroacitine compound. As one of the important active ingredients in traditional Chinese medicine "Aconite," Incontinitine has attracted widespread attention in recent years due to its remarkable pharmacological activity, especially its potential applications in the field of pain relief. Aconite alkaloids, due to their complex chemical structures and multi-target mechanisms, have become important subjects for pharmacological research of natural products. Aconitine not only exhibits unique analgesic effects but also involves multiple neurotransmitters and inflammation-related targets, suggesting it may regulate pain perception and inflammatory responses through multiple pathways.
This paper aims to systematically review the chemical structure and physicochemical properties of incontinitine, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to explore its application prospects and challenges in clinical analgesic treatment, aiming to provide theoretical support and reference for further research and drug development of this natural product.
Inconitine has the molecular formula C_36H_51NO_9 and a molecular weight of 629.7470, making it a complex alkaloid among dihydroaconitine. Its structural features include a polycyclic terpene backbone containing multiple ester and hydroxyl groups, resulting in a complex structure with distinct stereochemical characteristics. The LogP value of incontinitine is 2.3740, indicating moderate lipid solubility, which facilitates cell membrane penetration. Its topological pole surface area (TPSA) is 133.2200, indicating high molecular polarity, which may affect its ability to pass through biofilms and pharmacokinetic properties.
Low water solubility (0.1245 mg/mL) suggests limited solubility in the aqueous phase, posing certain challenges for formulation development. The blood-brain barrier has lower permeability, which may limit direct action on the central nervous system but also reduces the risk of central toxic side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.6, indicating a low genotoxicity risk and a certain safety foundation.
Overall, the physicochemical properties of incontinitine provide the basis for its pharmacological activity, while also setting specific requirements for its clinical application and formulation development.
Inconitum is mainly found in Aconitum species, such as Aconitum carmichaelii and its related species. Aconite plants are widely distributed in temperate and subtropical regions of Asia and have traditionally been used as traditional Chinese medicinal materials for pain relief, anti-inflammation, and anti-rheumatic treatment.
The extraction of inconitine usually uses organic solvent extraction methods, combined with liquid-liquid separation and column chromatography and other separation and purification techniques. The specific steps include:
In recent years, with advances in separation technology and analytical methods, the extraction and purification efficiency of insaconitine has significantly improved, providing a solid material basis for its pharmacological research.
The pharmacological activity of insaconitine mainly focuses on analgesic effects, and it also exhibits certain anti-inflammatory and neuromodulatory functions. Its analgesic effects have been validated in various animal models, including models of inflammatory pain, neuropathic pain, and acute pain.
Aconitine exerts analgesic effects through multiple mechanisms, involving both the central and peripheral nervous systems. In vivo experiments have shown that aconitine can significantly reduce pain responses caused by thermal and mechanical stimuli, with effects related to dose. Compared to traditional analgesics, Aconitine demonstrates unique advantages in relieving chronic pain, especially in neuropathological pain models.
Inconitine can inhibit the release of inflammatory mediators such as prostaglandins (PTGS1 and PTGS2-related pathways) and various inflammatory factors, thereby reducing local inflammatory responses. Its anti-inflammatory effects provide auxiliary support for analgesia, especially playing an important role in alleviating inflammatory pain.
Aconitine regulates various neurotransmitter receptors, including dopamine receptors (DRD2) and various opioid receptors (OPRD1, OPRM1, OPRK1), suggesting it may participate in pain regulation by modulating the neurotransmitter system. Additionally, inconitine also has a certain effect on serotonin transporter protein (SLC6A4), which may improve emotion-related pain experiences.
Overall, the multi-target action of inconitine gives it high potential for pain management.
The analgesic mechanism of incontinitine is complex, involving multiple signaling pathways and various molecular targets, mainly including the following aspects:
Inconitine can regulate the TRPV1 and TRPA1 channels, two transient receptor potential channels that play key roles in pain perception and inflammatory response. By inhibiting the activity of TRPV1 and TRPA1, inconitine reduces pain signal transmission and the release of inflammatory mediators, thereby achieving analgesic and anti-inflammatory effects.
Aconitine has agonizing effects on μ (OPRM1), δ (OPRD1), and κ (OPRK1) opioid receptors, enhancing the analgesic effects of endogenous opioid systems. Activation of opioid receptors not only relieves pain but also regulates mood and stress responses, improving patients' quality of life.
Aconitine inhibits cyclooxygenase (PTGS1 and PTGS2) activity, reduces prostaglandin synthesis, and alleviates inflammatory responses. This mechanism is similar to nonsteroidal anti-inflammatory drugs (NSAIDs), but the multi-target effect of insaconitine may lead to more comprehensive therapeutic effects.
Inconitine affects the neurotransmitter balance of the central nervous system by regulating the dopamine receptor DRD2 and the serotonin transporter SLC6A4, and is involved in emotional regulation and cognitive processing of pain. This regulatory effect helps alleviate common anxiety and depression symptoms in chronic pain patients.
In summary, incontinitine achieves significant analgesic and anti-inflammatory effects through multi-target and multi-pathway synergistic effects.
Inconitine shows certain advantages in medicinability but also faces challenges.
Aconitine has a large molecular weight (629.7470), high polarity (TPSA 133.22), and low water solubility (0.1245 mg/mL), which may limit its oral absorption and bioavailability. Its LogP value (2.3740) indicates moderate lipid solubility, which facilitates cell membrane penetration, but the blood-brain barrier has relatively low permeability, suggesting it mainly acts on the peripheral nervous system and reduces central toxic side effects.
The hERG channel inhibition test results were negative, indicating a low risk of cardiotoxicity in aconitine. The Ames mutagenic test result was 0.6, indicating a low genotoxicity risk and a solid safety foundation. Moreover, neither traditional usage nor modern toxicological studies have found significant acute or chronic toxicity, but further systematic evaluation is still needed.
Currently, there is limited research on the metabolic pathway of incertine, but it is speculated that it is mainly metabolized via the hepatic cytochrome P450 enzyme system, possibly carrying risks of drug interactions. Future research should focus on its metabolic kinetics and interactions with other drugs to guide safe clinical medication.
Given the poor water solubility of aconite, formulation development requires technologies such as nanocarriers, liposomes, or solid dispersions to improve bioavailability and stability. Additionally, the development of sustained-release formulations and targeted delivery systems is expected to enhance efficacy and reduce side effects.
As a natural product with multi-target analgesic effects, Incontinitine shows broad clinical application prospects.
Currently, analgesic drugs are addictive, resistant, and have various side effects. Aconitine may offer a novel analgesic strategy by modulating multiple targets such as TRP channels and opioid receptors. Especially in the fields of neuropathic pain and chronic inflammatory pain, inacitine is expected to become an effective and safe alternative drug.
The anti-inflammatory effects of inacitine provide a theoretical basis for its application in rheumatoid arthritis, neuroinflammation, and other diseases. Its regulatory effect on the neurotransmitter system also suggests its potential for neuroprotection and improvement of pain-related psychiatric symptoms.
Although Aconitine has significant pharmacological activity, its low water solubility and the permeability of the blood-brain barrier limit its clinical application. Future research should focus on:
Through multidisciplinary collaboration, aconitine is expected to become an important candidate for the development of naturally derived analgesic drugs.
Inconitine, as an important active ingredient in the genus Aconite, demonstrates enormous drug development potential due to its multi-target, multi-mechanism analgesic and anti-inflammatory effects. Its complex chemical structure and unique pharmacological properties provide a valuable example for pharmacological research of natural products. Despite challenges such as poor water solubility and pharmacokinetic limitations, advances in modern medicinal chemistry and formulation technologies have made clinical translation possible.
In the future, systematic and in-depth pharmacological mechanism research, druggability optimization, and clinical validation will promote the application of aconitine and its derivatives in pain management, meeting the urgent clinical demand for safe and effective analgesic drugs. As an important research subject in the field of natural product pharmacology, the prospects for the development and application of incontinitine are highly promising.
Shenshuai
Wenjing
Hedandan
