Synonym name: Tokoro-base II
Catalogue No.: BP0337
Cas No.: 5066-78-4
Formula: C₂₅H₄₁NO₆
Mol Weight: 451.604
Botanical Source: Alkaloid from Aconitum chasmanthum, Aconitum subcuneatum, Aconitum yesoense, Aconitum crassicaule, Aconitum franchetii, Aconitum teipeicum, Aconitum sachalinense var. compactum, Aconitum forrestii, Aconitum pseudogeniculatum and others (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℃

Introduction/Overview

Chasmanine is a diterpene alkaloid with significant pharmacological activity, mainly obtained from the roots of Aconitum crassicaule plants. Aconite plants have a long history of use in traditional Chinese medicine, widely used for pain relief, anti-inflammatory, and anti-rheumatic diseases. Zhanhua Aconite, as a hydrogenated derivative of aconite alkaloids, has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and multi-target pharmacological activity. This paper systematically reviews the chemical structure and physicochemical properties of Zhanhua Aconitium, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide a theoretical foundation and practical guidance for related research.

Chemical structure and physicochemical properties

Zhanhua Aconitin has the chemical formula C25H41NO6 and a molecular weight of 451.6, classified as a diterpene alkaloid compound. Its structural features include diol groups, tertiary and secondary alcohol functional groups, as well as a bridged organic heteropolycyclic system containing tertiary amino groups, exhibiting a complex stereochemical configuration. This compound is derived from the hydride of aconitan, which has the typical aconitone backbone and imparts strong biological activity.

In terms of physicochemical properties, Zhanhua Aconitin has a LogP value of about 1.77, indicating moderate lipid solubility, which is beneficial for cell membrane penetration. Its topological polar surface area (TPSA) is 100.99 Ų, with 7 hydrogen bond acceptors, demonstrating strong polarity and hydrogen bond formation ability, which significantly affects its binding to biological macromolecule targets. Although its blood-brain barrier penetration is still unclear, its physicochemical properties suggest it may have certain potential for central nervous system activity.

Plant Origins and Extraction Methods

Zhan Hua Aconitum mainly comes from the roots of Aconitum crassicaule, especially Aconitum crassicaule. Aconite plants are widely distributed in temperate and subarctic regions of Asia and possess abundant alkaloid resources. Traditionally, the roots of these plants are dried and used in traditional Chinese medicine preparations.

The process for extracting Zhanhua Aconitin typically includes the following steps: First, using organic solvents (such as methanol, ethanol, or ethyl acetate) to extract dried plant roots by reflux. After concentration, the extract is adjusted with acid-base adjustment for liquid-liquid distribution to enrich alkaloid components. Subsequently, column chromatography techniques (such as silica gel columns and C18 reversed-phase columns) were used to separate and purify the crude extracts, combined with high-performance liquid chromatography (HPLC) and mass spectrometry (MS) identification, ultimately obtaining high-purity Zhanhua Aconit. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, reduced solvent usage, and aligned with the concept of green chemistry.

Pharmacological activity research

Research on the pharmacological activity of Zhanhua Aconitin mainly focuses on analgesic and food resistance effects. As a natural diterpene alkaloid, it demonstrates multi-target modulation capabilities, especially showing potential in pain relief related to neurological diseases.

Analgesic effect

Multiple in vivo and in vitro experiments have shown that Zhanhua Aconitin has significant analgesic effects on various pain models. Its mechanism involves multiple neurotransmitter systems and receptor pathways, regulating the transmission and perception of pain signals. Compared to traditional opioid analgesics, Zhanhua Aconitin may act through non-opioid receptor pathways, reducing the risk of dependence and resistance.

Effect of repelling food

Zhanhua Aconitin also exhibits significant food-repellent activity, which can suppress the feeding behavior of certain insects and pests on plants, giving it potential value for pesticide development. Its effects may be related to interference with the insect's nervous system, and the specific mechanisms require further research.

Other potential activities

In addition to analgesic and food-retrieving effects, Zhanhua Aconitin may also possess anti-inflammatory, antioxidant, and neuroprotective activities. Preliminary in vitro experiments have shown its inhibitory effect on inflammatory mediators, suggesting its potential for application in inflammation-related diseases.

Mechanism of action and molecular targets

The pharmacological effects of Zhanhua Aconitin involve multiple molecular targets, especially demonstrating multi-target coordinated regulation in its analgesic mechanism. The main targets include:

• TRPV1 (transient receptor potential vanillate subfamily member 1): TRPV1 is a key ion channel for pain perception. Zhanhua Aconitin may inhibit pain signal transmission by modulating TRPV1 activity.
• CNR1 (Cannabinoid Receptor 1): CNR1 is involved in pain regulation in the central nervous system. Zhanhua Aconitin may activate or modulate this receptor to exert analgesic effects.
• OPRD1, OPRM1, OPRK1 (δ, μ, κ opioid receptors): These opioid receptors are targets of traditional analgesics. Zhanhua Aconitin may enhance its analgesic effect by partially stimulating or modulating these receptors.
• PTGS1 and PTGS2 (cyclooxygenase-1 and -2): As important enzymes in inflammatory responses, Zhanhua Aconitin inhibits PTGS enzyme activity, which may reduce the production of inflammatory mediators and relieve inflammatory pain.
• TRPA1 (Transient receptor potential vanillic acid subfamily member A1): TRPA1 is involved in the perception of chemical and mechanical pain, and Zhanhua Aconit's regulation helps control various pain types.
• SLC6A4 (serotonin transporter): By influencing serotonin reuptake, Zhanhua Aconitin may regulate mood and pain perception, providing auxiliary analgesia.
• DRD2 (Dopamine D2 receptor): The dopamine system is involved in pain regulation and emotional control. The effect of Zhanhua Aconitum on DRD2 may influence the emotional dimension of pain.

The synergistic effect of these multi-target drugs gives Zhanhua Aconitin a more comprehensive analgesic effect and may reduce side effects and resistance issues associated with single-target drugs.

Druggability evaluation and pharmacokinetics

The drug-making evaluation of Zhanhua Wutouning is still in its early stages. Its molecular weight is 451.6, meeting the Lipinski rule molecular weight requirements, with a LogP of 1.77, indicating moderate lipid solubility and favorable oral absorption. TPSA is 100.99 Ų, indicating appropriate polarity, which may affect its bioavailability and distribution.

A hydrogen bond receptor count of 7 indicates strong potential for binding to biological targets, but may also affect cell membrane penetration. Currently, there is no clear data on safety indicators such as blood-brain barrier penetration, hepatotoxicity, cardiotoxicity, hERG channel inhibition, and mutagenicity (Ames assay), which limits the progress of clinical development.

In terms of pharmacokinetics, there is a lack of systematic studies on metabolism and excretion in vivo. Based on its structural speculation, Zhanhua Aconitin may be metabolized via the hepatic cytochrome P450 enzyme system, but its metabolites and activity still require further study. In addition, parameters such as its in vivo half-life, bioavailability, and tissue distribution urgently need to be clarified through animal experiments and preclinical trials.

Prospects and outlooks for clinical applications

As a natural diterpene alkaloid, Zhanhua Aconitin has broad clinical application potential due to its remarkable analgesic effects and multi-target mechanism. Especially in the treatment of chronic pain, neuropathic pain, and inflammation-related pain, Zhanhua Aconitum may be a powerful supplement to non-opioid analgesics, reducing dependence and side effects associated with traditional analgesics.

Moreover, its food-repelling activity offers new ideas for agricultural pest control and holds potential for developing green pesticides. In the future, in-depth analysis of its pharmacological mechanisms should be strengthened, extraction and synthesis processes optimized, yield and purity improved, and medicinal safety ensured.

The key to clinical application lies in systematic pharmacokinetic and toxicological studies, establishing safe dose ranges and administration regimens. By combining modern drug design technologies, such as structural modification and drug carrier systems, it is expected to enhance efficacy and safety. Multicenter clinical trials will be necessary steps to validate its clinical efficacy and safety.

Conclusion

Zhanhua Aconitin, as an important diterpene alkaloid in Aconite species, exhibits a unique chemical structure and multi-target analgesic activity. It holds significant research value and development potential in the field of natural product pharmacology. Although data on its pharmacokinetics and safety are still incomplete, its diverse pharmacological effects and favorable druggability parameters provide a solid foundation for its clinical translation. In the future, through systematic pharmacological and toxicology research and clinical trials, Zhanhua Aconite is expected to become a new generation of safe and effective analgesic and green pesticide, contributing to human health and agricultural production.