Product name: Benzoylhypaconine
Synonym name: Deacetylhypaconitine
Catalogue No.: BP0245
Cas No.: 63238-66-4
Formula: C₃₁H₄₃NO₉
Mol Weight: 573.683
Botanical Source: Aconitum carmichaelii Debx.
Physical Description:
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

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

Introduction/Overview

Benzoylhypaconitine (CAS number: 63238-66-4) is a monoester alkaloid derived from Aconitum spp. As an important member of the Aconitum alkaloid family, Benzoylhypaconitine has significant pharmacological activity and toxicity characteristics in traditional Chinese medicine. Aconitum plants are widely used in the treatment of various diseases such as pain relief, anti-inflammatory, and rheumatism due to their complex alkaloid composition, but their toxicity also limits their widespread clinical application. Benzoyl aconitine, as the main pharmacological and toxic component of aconitine alkaloids, has attracted increasing attention in the field of natural product pharmacology in recent years, especially in the potential therapeutic value of neurological diseases such as anxiety disorders.

This article aims to systematically review the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity and mechanism of action, pharmacological evaluation and pharmacokinetic characteristics of benzoyl aconitine, and explore its clinical application prospects in neurological and psychiatric disorders such as anxiety disorders. By integrating existing literature, provide theoretical basis and research direction for pharmacological research and new drug development of this natural product.

Chemical structure and physicochemical properties

Benzoyl aconitine belongs to the dihydroaconitine monoester alkaloids, with a molecular formula of C31H39NO9 and a molecular weight of 573.68 Da. Its chemical structure is characterized by the presence of benzoyl monoesters attached to the aconitine skeleton, endowing it with unique physicochemical properties. The LogP value is 3.08, indicating that it has moderate lipid solubility and may facilitate passive diffusion through the cell membrane. The polar surface area (TPSA) is 136.96 Å ², and the number of hydrogen bond acceptors is 9, indicating that the molecule has strong polarity and hydrogen bonding ability, which is of great significance for its binding to biomolecule targets.

The physicochemical properties of benzoyl aconitine determine its absorption, distribution, and metabolic behavior in vivo. However, there is currently a lack of systematic research on its safety indicators such as blood-brain barrier penetration ability, hepatotoxicity, cardiotoxicity, and hERG channel inhibition, and further experimental verification is urgently needed.

Plant sources and extraction methods

Benzoyl aconitine is mainly found in plants of the Aconitum genus, especially attached to the traditional Chinese medicinal herb Aconitum carmichaelii Debx. and its related species. Aconitum plants are widely distributed in southwestern China and the Himalayan region, and are widely used in traditional Chinese medicine clinical practice due to their complex alkaloid composition.

The traditional method for extracting benzoyl aconitine often uses alcohol solvents (such as ethanol and methanol) to reflux extract dried plant tubers, followed by separation and purification through acid-base separation, liquid-liquid extraction, and column chromatography techniques. The application of modern extraction techniques such as ultrasound assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) separation technology has significantly improved extraction efficiency and purity.

During the extraction process, the stability of benzoyl aconitine is greatly affected by pH and temperature. Suitable extraction conditions and subsequent purification processes are crucial to ensure the integrity of its active ingredients. In addition, the identification methods mainly rely on modern analytical methods such as mass spectrometry (MS), nuclear magnetic resonance (NMR), and infrared spectroscopy (IR) to ensure the structural confirmation and purity evaluation of compounds.

Pharmacological activity research

Benzoyl aconitine, as the main pharmacological component of aconitine alkaloids, exhibits various biological activities, and its potential application value in neurological diseases has attracted much attention.

1. Anti anxiety effect
   In recent years, in vitro and in vivo studies have shown that benzoyl aconitine exerts significant anti anxiety effects by regulating various neurotransmitter receptors and ion channels. Its targets involve acetylcholinesterase (ACHE), nicotinic acetylcholine receptor alpha 7 subtype (CHRNA7), opioid delta receptor (OPRD1), and adenosine A3 receptor (ADORA3), regulating neural excitability and neuroprotective mechanisms.

2. Analgesic and anti-inflammatory activity
   Benzoyl aconitine exhibits analgesic effects by affecting the functions of sodium and calcium channels, inhibiting nerve conduction. In addition, it regulates the endothelin receptors (EDNRA, EDNRB) and the sigma 1 receptor (SIGMAR1), participates in the regulation of inflammatory responses, and has potential anti-inflammatory effects.

3. Neuroprotective effect
   By regulating the GRM2 receptor related to glutamate metabolism, benzoyl aconitine may be involved in neuronal protection and synaptic plasticity regulation, reducing neurotoxic damage and having neuroprotective potential.

4. Toxicity characteristics
   As an important member of aconitine alkaloids, benzoyl aconitine has certain cardiac toxicity and neurotoxicity, mainly manifested as excessive activation of sodium channels, leading to arrhythmia and abnormal neural excitation. The toxic dose is close to the pharmacological dose, which limits the safety window of its clinical application.

Mechanism of action and molecular targets

The pharmacological activity of benzoyl aconitine depends on its interactions with multiple molecular targets, especially its multi-target regulatory effect in the nervous system.

1. ABCB1 (P-glycoprotein)
   As an efflux pump on the cell membrane, ABCB1 affects the intracellular accumulation and blood-brain barrier penetration of benzoyl aconitine. Benzoyl aconitine may affect its own and other drug pharmacokinetic behaviors by regulating ABCB1 activity.

2. TOP1 (Topoisomerase I)
   Although TOP1 mainly participates in DNA topology regulation, the potential interaction between benzoyl aconitine and TOP1 suggests that it may affect cell proliferation and apoptosis processes, indirectly regulating neuronal function.

3. EDNRA/EDNRB (endothelin receptor A/B)
   Benzoyl aconitine participates in the regulation of inflammation and pain signals by modulating endothelin receptors, affecting vascular constriction and nerve conduction.

4. CHRNA7 (nicotinic acetylcholine receptor alpha 7 subtype)
   This receptor plays an important role in regulating neuroinflammation and cognitive function, and the regulation of CHRNA7 by benzoyl aconitine contributes to its anti anxiety and neuroprotective effects.

5. OPRD1 (opioid delta receptor)
   As a subtype of opioid receptor, OPRD1 is involved in pain regulation and emotion control, and benzoyl aconitine may exert analgesic and anti anxiety effects by activating or regulating this receptor.

6. ADORA3 (adenosine A3 receptor)
   This receptor is involved in anti-inflammatory and neuroprotective effects, and the action of benzoyl aconitine on it may enhance its anti-inflammatory and neuroprotective potential.

7. SIGMAR1 (σ 1 receptor)
   As an important target for neuroprotection and emotion regulation, the binding of benzoyl aconitine to the σ 1 receptor helps regulate calcium homeostasis and signal transduction in nerve cells.

8. ACHE (Acetylcholinesterase)
   By inhibiting ACHE, benzoyl aconitine can increase acetylcholine levels, enhance cholinergic nerve conduction, and improve anxiety and cognitive impairment.

9. GRM2 (metabolic glutamate receptor 2)
   This receptor regulates glutamate neurotransmission, and the regulation of GRM2 by benzoyl aconitine helps alleviate the pathological state associated with excessive neural excitability.

In summary, benzoyl aconitine achieves its complex pharmacological effects through multi-target and multi pathway synergistic effects, especially with significant potential for application in neurological diseases.

Evaluation of drug properties and pharmacokinetics

The pharmacological evaluation of benzoyl aconitine includes physicochemical properties, safety, and pharmacokinetic parameters.

1. Physicochemical properties
   The molecular weight of 573.68 Da is slightly higher than the ideal range of traditional oral drugs (<500 Da), but the LogP value of 3.08 is moderate, which is beneficial for cell membrane permeation. A high TPSA (136.96 Å ²) suggests a high polarity, which may affect oral absorption and blood-brain barrier penetration ability.

2. safety indicator
   At present, there is a lack of systematic data on liver toxicity, cardiac toxicity, and hERG channel inhibition. Considering the common risk of cardiac toxicity of aconitine alkaloids, the safety of benzoyl aconitine needs to be evaluated as a priority. The results of Ames mutagenicity test have not been reported yet, and additional genotoxicity studies are needed.

3. pharmacokinetics
   The existing literature lacks data on the absorption, distribution, metabolism, and excretion (ADME) of benzoyl aconitine. Its high polarity and molecular weight may limit oral bioavailability, and it is unclear whether it can effectively cross the blood-brain barrier. The metabolic pathway may involve hydroxylation and ester hydrolysis of liver enzymes, and the activity and toxicity of metabolites need further investigation.

4. Potential for drug interactions
   Due to its potential interaction with transporters such as ABCB1, the interaction risk of benzoyl aconitine in multi drug combination therapy needs to be considered.

In summary, there are certain challenges in the pharmacological properties of benzoyl aconitine, and in-depth research on its safety and pharmacokinetic characteristics is the key to its clinical development.

Clinical application prospects and prospects

Benzoyl aconitine, as an important component of aconitine alkaloids, exhibits unique multi-target regulatory advantages in the treatment of neurological and psychiatric disorders such as anxiety disorders. By regulating acetylcholine, glutamate, opioid receptors, and the endothelin system, it may improve nerve conduction imbalance and neuroinflammatory states, providing new ideas for drug treatment of anxiety disorders.

However, the clinical application of benzoyl aconitine still faces many challenges:

• Security risk Cardiotoxicity and neurotoxicity are the main limiting factors of aconitine alkaloids, and benzoyl aconitine alkaloids need to be structurally modified or dosage form optimized to reduce toxicity.
• Pharmacokinetic defects The low oral absorption rate and unclear blood-brain barrier penetration ability limit its therapeutic potential for neurological diseases.
• Insufficient clinical research Currently, there is a lack of systematic clinical trial data, and there is an urgent need to conduct preclinical and clinical studies on pharmacodynamics, safety, and pharmacokinetics.

Future research directions include:

• Improve the selectivity and safety of benzoyl aconitine through chemical modification.
• Utilizing novel drug delivery systems such as nanocarriers to improve their bioavailability and targeting.
• Thoroughly analyze its multi-target mechanism of action and screen potential synergistic targets.
• Develop derivative designs based on benzoyl aconitine and explore safer and more effective therapeutic molecules.

Overall, as a candidate molecule for natural product drug development, benzoyl aconitine has important research and application value, but its clinical translation needs to overcome safety and pharmacokinetic bottlenecks.

Conclusion

Benzoyl aconitine, as a key alkaloid in Aconitum plants, has shown broad prospects in the treatment of anxiety disorders and related neurological diseases due to its complex chemical structure and multi-target pharmacological activity. Although its toxicity risks and pharmacokinetic properties limit its direct clinical application, with the assistance of modern medicinal chemistry and drug delivery technologies, benzoyl aconitine and its derivatives are expected to become important candidates for the treatment of novel neurological and psychiatric disorders.

Future research should focus on systematically evaluating its safety, clarifying its mechanism of action, optimizing pharmacokinetic characteristics, and promoting preclinical and clinical studies to achieve the successful transformation of this traditional natural product into modern drugs, providing new strategies and choices for the treatment of anxiety disorders and other diseases.