Synonym name: Bulleyaconitine A; Crassicauline I; 3-Deoxyyunaconitine
Catalogue No.: BP0403
Cas No.: 79592-91-9
Formula: C₃₅H₄₉NO₁₀
Mol Weight: 643.774
Botanical Source: Alkaloid from Root of Aconitum crassicaule, Aconitum forrestii, Aconitum pseudogeniculatum and Aconitum dolichorhynchum var. subglabratum (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.

HPLC of Crassicauline A

HNMR of Crassicauline A

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

Introduction/Overview

Crassicaulin A (CAS No.: 79592-91-9) is a natural alkaloid product extracted from the roots of Aconitum plants. Aconite plants have a long history of use in traditional Chinese medicine due to their complex alkaloid components, especially showing significant pharmacological activity in analgesic, anti-inflammatory, and adjunctive treatments for neurological diseases. As one of the important active ingredients in Aconite, Caowu Jia has attracted widespread attention in recent years due to its unique biological functions. Previous studies have shown that mesaoxin not only exhibits significant food-repelling activity against the agricultural pest Eucophyllus sclerotifis (EC50 value 1134.5 ppm), but also demonstrates potential pharmacological effects in the field of analgesia, involving multiple molecular targets related to pain regulation, such as TRPV1, CNR1, and OPRD1.

This review aims to systematically summarize the chemical structure and physicochemical properties of meloaoxin, plant origin and extraction process, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and, combined with its potential application value in analgesic treatment, explore its future development prospects and challenges, providing a theoretical foundation and reference for related research.

Chemical structure and physicochemical properties

Methyl oxaoli is a complex alkaloid with a molecular weight of 643.76, characterized by a high molecular weight and a relatively complex molecular structure. Its LogP value is 3.51, indicating moderate lipophilusity, which facilitates penetration of cell membranes but is not easily overly lipophilic, potentially affecting its distribution and metabolism in vivo. TPSA (Topological Polar Surface Area) is 136.95 Ų, indicating that the molecule has a large number of polar groups. Binding to its hydrogen bond acceptor number reaches 10, indicating that the sulfur methyl acid molecule contains abundant polar functional groups, which is significant for binding to biological macromolecule targets.

Structurally, mecoamethylene belongs to the Aconite alkaloid family, typically containing polycyclic structures and nitrogen-containing heterocycles, a structural feature that gives it strong biological activity. Its complex cyclic framework and multipolar groups enable its binding to multiple protein targets, but also bring synthetic difficulties and pharmacokinetic challenges.

Plant Origins and Extraction Methods

Aconitum is mainly found in the roots of Aconitum species, especially abundant in Aconitum kusnezoffii Reichb. Aconite plants are widely distributed in temperate and subarctic regions of Asia and are extensively collected and studied for their medicinal value. In traditional Chinese medicine, Aconite root is used as a medicinal herb for pain relief, anti-inflammation, and anti-rheumatic effects, but due to its high toxicity, modern research focuses on isolating and purifying its active ingredients to reduce toxic side effects.

Common methods for extracting chloromethylene include solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. Ethanol or methanol is generally used as extraction solvents, with ultrasound-assisted extraction improving efficiency. Afterwards, silica gel column chromatography or reversed-phase C18 columns were used for separation and purification, combined with mass spectrometry and nuclear magnetic resonance (NMR) technology for structural identification. In recent years, supercritical fluid extraction and microwave-assisted extraction technologies have also been attempted to extract chloromethylene, aiming to improve purity and yield while reducing solvent usage and environmental pollution.

Pharmacological activity research

Activity of repelling foods

Oxyaoxin showed significant food-repellent activity against adult Eucosis samurus, with an EC50 value of 1134.5 ppm, indicating its potential application value in agricultural pest control. This activity may be related to interference with the pest's neural conduction or taste receptors, though the specific mechanism remains to be further elucidated.

Analgesic effect

Research on acetamethyl in analgesia is relatively preliminary, but its targets cover various proteins related to pain perception and regulation, including TRPV1 (capsaicin receptor), CNR1 (cannabinoid receptor 1), OPRD1 (δ-opioid receptor), PTGS1/PTGS2 (cyclooxygenase 1/2), TRPA1 (transient receptor potential channel A1), SLC6A4 (serotonin transporter), OPRM1 (μ-opioid receptor), OPRK1 (κ-opioid receptor) and DRD2 (dopamine D2 receptor). These targets play key roles in pain transmission, inflammatory responses, and neural regulation, suggesting that meoxamethylene may achieve analgesic effects through the synergistic action of multiple targets.

Other pharmacological activities

Apart from analgesic and repellent activity, other pharmacological effects of meoxamine have not been systematically studied. Given its structural characteristics and target profile, it is expected to conduct in-depth exploration in areas such as anti-inflammation, neuroprotection, and mental disorder regulation in the future.

Mechanism of action and molecular targets

The analgesic mechanism of mesaurophyllamine may involve the regulation of multiple molecular targets, as detailed below:

1. TRPV1 and TRPA1: As ion channels sensing heat and chemical stimuli, TRPV1 and TRPA1 play central roles in the primary sensation of pain and the inflammatory response. Methyl sulfur may reduce nerve endings excitability by regulating the activity of these channels, thereby alleviating pain.

2. Opioid receptors (OPRD1, OPRM1, OPRK1): The opioid receptor family is a classic analgesic target that mediates the analgesic effects of endogenous and exogenous opioids. Binding to these receptors may enhance endogenous analgesic signaling, exerting central and peripheral analgesic effects.

3. CNR1 (Cannabinoid Receptor 1): Involved in regulating pain, mood, and inflammatory responses. Acetron may activate or regulate CNR1, exerting analgesic and anti-inflammatory effects.

4. PTGS1/PTGS2 (cyclooxygenase 1/2): involved in the synthesis of inflammatory mediator prostaglandins, regulating inflammation and pain responses. Acetronin may inhibit the activity of these two enzymes, reducing the generation of inflammatory mediators.

5. SLC6A4 (serotonin transporter) and DRD2 (dopamine D2 receptor): involved in neurotransmitter regulation, affecting mood and pain perception. Acetronin may improve pain-related mood disorders by regulating these neurotransmitter systems.

In summary, the analgesic effect of Cauwujia may result from multi-target, multi-pathway synergistic effects, including direct regulation of peripheral nerves as well as neurotransmitter regulation of the central nervous system.

Druggability evaluation and pharmacokinetics

The druggability parameters of mesauroxin showed a relatively large molecular weight (643.76) and a LogP of 3.51, indicating moderate lipid solubility, which theoretically facilitates cell membrane penetration, but its higher polarity and number of hydrogen bond receptors (10) may limit its oral bioavailability. Additionally, mechoujiazin is predicted to be difficult to cross the blood-brain barrier, suggesting that its analgesic effect may depend more on peripheral mechanisms and reduce the risk of toxic side effects in the central nervous system.

Currently, safety data on the hepatotoxicity, cardiotoxicity (including hERG channel inhibition), and genotoxicity (Ames assay) of melanin are lacking and require further systematic evaluation. Regarding pharmacokinetics, there are no publicly reported ADME (ADME) characteristics. Future research should focus on its in vivo metabolic pathways, half-life, and toxicological characteristics of potential metabolites.

Due to the complex structure, high difficulty of synthesis, and unknown toxicity, drug development requires overcoming multiple challenges such as synthesis process optimization, toxicity assessment, and pharmacokinetic improvement.

Prospects and outlooks for clinical applications

As an important active ingredient in Aconite root, meolut shows broad application prospects thanks to its multi-target analgesic mechanism and significant repellent activity. In the field of analgesic treatment, meawujiazin may be a candidate molecule for new analgesics, especially suitable for peripheral pain management, potentially reducing the risk of dependence and side effects associated with traditional opioids.

In addition, the food-repellent activity of mesaurophyllin provides a natural, environmentally friendly candidate for agricultural pest control, helping to reduce the use of chemical pesticides and promote the development of green agriculture.

Future research should focus on the following directions:

1. Systematic pharmacological and toxicological studies: clarify the safety profile of melomethyl, especially liver and cardiac toxicity assessments, to ensure its clinical safety in practice.

2. Pharmacokinetic optimization: Improving bioavailability and in vivo stability through structural modification or drug carrier technologies.

3. In-depth analysis of the mechanism of action: Using molecular biology and structural biology methods, the binding patterns of meolin and its targets and the signaling pathway regulatory mechanisms were elucidated.

4. Preclinical and clinical research: Conduct animal models and human trials to verify analgesic efficacy and safety, laying the foundation for clinical application.

5. Synthesis and preparation process optimization: Develop efficient and green synthesis routes and extraction and purification technologies to ensure drug supply and stable quality.

Conclusion

As an important alkaloid in Aconite root, melanin demonstrates its potential as a novel analgesic drug and agricultural food rejection agent due to its unique chemical structure and multi-target analgesic activity. Although their pharmacological mechanisms and safety are not yet fully understood, their multi-target mode of action offers new ideas for developing highly effective, low-side effect analgesics. In the future, through systematic pharmacological research, toxicological evaluation, and clinical validation, mesaoxin is expected to achieve widespread application in the pharmaceutical and agricultural fields, driving innovation in natural product drugs.