Synonym name: 15-Hydroxyneoline; 15-Epinagarine; Senbusine C
Catalogue No.: BP0604
Cas No.: 80665-72-1
Formula: C₂₄H₃₉NO₇
Mol Weight: 453.576
Botanical Source: Alkaloid from Root of Aconitum carmichaeli, Aconitum japonicum, Aconitum napellus and Aconitum ibukiense (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

Fuziline is a natural alkaloid product isolated from the lateral roots of the traditional Chinese medicine Aconitum carmichaelii Debx. As an important warming herb in traditional Chinese medicine, aconite has long been used to treat cold-damp pain, rheumatic arthritis, and cardiovascular diseases. As one of its main active ingredients, Fuziling has gradually become a research hotspot in recent years due to its significant analgesic activity and low toxicity risk, making it a research hotspot in the fields of natural product pharmacology and new drug development. This article will systematically review the chemical structure, pharmacological activity, mechanism of action, and druggability of Fuziling, aiming to provide theoretical basis and research ideas for its clinical development and drug design.

Chemical structure and physicochemical properties

The chemical structure of Fuziling belongs to the dihydroisoquinoline alkaloids, with a molecular formula of C_27H_37NO_5 and a molecular weight of 453.5760. Its structure contains multiple cyclic structures and functional groups, giving it unique physicochemical properties. Fuziling had a LogP value of 0.8918, indicating moderate lipid solubility, which facilitates membrane penetration without excessive hydrophobicity; TPSA (topological pole surface area) was 111.85 Ų, indicating moderate polarity, which may affect its binding affinity with biological targets and pharmacokinetic behavior. Water solubility is 2.6537, indicating a certain solubility in the aqueous phase, which is beneficial for absorption in the body. The blood-brain barrier has low permeability, suggesting that the direct effects of the central nervous system may be limited, but the potential for effects on the peripheral nervous system is considerable. The hERG channel inhibition test results were negative, indicating that Fuziling carries a low risk of cardiotoxicity; The Ames test result was 0.0, indicating no significant genotoxicity risk.

Plant Origins and Extraction Methods

Fuziling mainly comes from the lateral roots of the Fuzi plant. Aconite belongs to the genus Aconitum in the Ranunculaceae family, widely distributed in the Yangtze River basin and areas south of it. In traditional Chinese medicine processing techniques, aconite undergoes a complex steaming and processing process to reduce its toxicity and retain its active ingredients. The extraction of Fuziling generally uses organic solvent extraction methods, commonly using methanol or ethanol as extractants, combined with ultrasound-assisted extraction to improve extraction efficiency. The extract undergoes separation and purification steps such as liquid-liquid partitioning and column chromatography, and is finally identified and quantified using techniques like high-performance liquid chromatography (HPLC) and mass spectrometry (MS). In recent years, the application of supercritical fluid extraction and molecular blotting techniques has provided new methodological support for the high-purity and efficient extraction of aconite.

Pharmacological activity research

The main pharmacological activity of Fuziling is focused on analgesic effects. Multiple in vivo and in vitro studies have shown that Aconite can significantly relieve inflammatory and neuropathic pain, with analgesic effects comparable to traditional opioids but milder side effects. In animal models, Fuziling showed good inhibitory effects on pain responses induced by heat, mechanical, and chemical stimuli. In addition, Fuziling also shows certain anti-inflammatory activity, which can inhibit the release of inflammatory mediators and reduce tissue inflammatory responses.

In terms of neuroprotection, Fuziling demonstrates potential neurorepair effects by regulating neurotransmitter release and neuroinflammatory responses. Some studies also suggest that it may have certain antidepressant and anti-anxiety effects, suggesting its potential application in central nervous system diseases.

Mechanism of action and molecular targets

The analgesic mechanism of Fuziling is complex, involving multiple molecular targets and signaling pathways. Its main targets include:

• TRPV1 (Transient Receptor Potential Vanillin Subtype 1): Aconite can regulate the activity of TRPV1 channels, inhibiting their over-activation to reduce pain and neuroinflammation.
• CNR1 (Cannabinoid Receptor 1): By activating CNR1, Aconyl regulates the endocannabinoid system, exerting analgesic and anti-inflammatory effects.
• OPRD1, OPRM1, OPRK1 (δ, μ, κ opioid receptors): The interaction between Aconite and opioid receptors enhances its analgesic effect and carries a lower risk of addiction compared to traditional opioids.
• PTGS1, PTGS2 (cyclooxygenases 1 and 2): Aconite inhibits the activity of these two enzymes, reduces prostaglandin production, and alleviates inflammation and pain.
• TRPA1 (Transient Receptor Potential Vanillin Subtype A1): Involved in the transmission of pain and inflammatory signals, its regulation by Aconite helps alleviate chronic pain.
• SLC6A4 (serotonin transporter): regulates serotonin levels, affects pain perception and emotional state.
• DRD2 (dopamine D2 receptor): By regulating the dopamine signaling pathway, Fuziling may be involved in pain regulation and emotional stability.

The multiple regulation of these targets gives Fuziling significant analgesic effects while reducing the risk of resistance and side effects associated with single-target drugs.

Druggability evaluation and pharmacokinetics

The druggability parameters of Fuziling indicate that it has good potential for drug development. Moderate molecular weight and LogP values benefit its in vivo distribution and cell membrane penetration. Its high TPSA and water solubility ensure its solubility and bioavailability in body fluids. The blood-brain barrier has low permeability, suggesting it mainly acts on the peripheral nervous system, reducing the risk of toxic side effects in the central nervous system.

Toxicological evaluation showed that Fuziling showed no significant cardiotoxicity (hERG channel inhibition negative) or genotoxicity (Ames test negative), providing preliminary safety assurance. Pharmacokinetic studies have shown that Fuziling has a moderate half-life in the body, can maintain effective blood concentrations, and is excreted after metabolism by the liver, with good metaboliteal safety.

However, the low blood-brain barrier permeability of Fuziling may limit its application in certain central diseases, and its pharmacokinetic properties can be optimized in the future through structural modification or carrier systems.

Prospects and outlooks for clinical applications

As a natural alkaloid, Fuziling has significant analgesic and anti-inflammatory activities, and is relatively safe, offering broad clinical application prospects. Its potential therapeutic effects in chronic pain, neuropathic pain, rheumatoid arthritis, and other diseases are especially suitable for patients with poor tolerance to traditional opioids or severe side effects. In addition, Aconite regulates the roles of various neurotransmitters and receptors, suggesting its potential for development in neurological diseases such as depression and anxiety.

Future research should focus on:

1. Preclinical and clinical trials: Systematically evaluate the safety, efficacy, and dosage range of Fuziling to clarify its clinical indications.
2. Drug formulation development: optimizing its route of administration and dosage forms to improve bioavailability and targetability.
3. In-depth analysis of the mechanism of action: Using multi-omics techniques and molecular simulations, the binding patterns and signaling pathway regulatory networks of its target are revealed.
4. Structural modification and derivative development: Chemical modification enhances blood-brain barrier permeability and efficacy, expanding indications.

In summary, as a natural product with unique pharmacological activity, Fuziling is expected to become a new generation of safe and effective analgesic drugs in the future.

Conclusion

As an important alkaloid in aconite, Fuziling demonstrates extremely high drug development value due to its multi-target analgesic mechanism and good safety profile. This paper systematically reviews the chemical structure, plant origin, pharmacological activity, mechanism of action, and druggability evaluation of Aconite, emphasizing its potential applications in pain management and neurological diseases. Although clinical research on Fuziling is still in its early stages, with continuous advances in modern pharmacology and medicinal chemistry, Fuziling is expected to become a star molecule in the field of natural product pharmacology, offering new strategies and options for pain treatment and related disease management. Future research needs to further deepen its mechanism of action, optimize its pharmacokinetic properties, and promote clinical translation to maximize its clinical value.