Product name: Hydroxyl-γ-isosanshool
Synonym name:
Catalogue No.: BP4110
Cas No.: 127514-62-9
Formula: C₁₈H₂₇NO₂
Mol Weight: 289.419
Botanical Source: Zanthoxyli pericarpium
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.

For Reference Standard and R&D, Not for Human Use Directly.

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

Introduction/Overview

Hydroxyl-γ γ-isosanshool (CAS number 127514-62-9) is a class found in cloves (Syzygium aromaticum) and horse chestnut clover (Hydrocotyle ). spp.) and other natural alkylamide compounds found in plants. As one of the main active ingredients in these plants, hydroxy-γ-isosancapacin has attracted attention for its unique chemical structure and significant biological activity. One of its most notable physiological effects is the induction of localized numbness, a characteristic that makes it highly significant in both traditional medicine and modern pharmacological research. In recent years, with in-depth analysis of the pharmacological mechanisms of natural products, the potential application value of hydroxy-γ-isosancapanine in anti-inflammatory and analgesic fields has gradually emerged, becoming a hot topic in pharmacological research of natural products.

This review aims to systematically summarize the chemical structure and physicochemical properties of hydroxy-γ-isosanjiaquin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its targeting role in anti-inflammatory diseases, it explores its clinical application prospects and development directions, providing comprehensive reference for researchers in related fields.

Chemical structure and physicochemical properties

Hydroxy-γ-isosancaphanin belongs to the alkylamide class of natural products, with a molecular formula of C18H27NO2 and a molecular weight of 289.4190. Its chemical structure features include a long-chain fatty amide backbone with a hydroxyl-modified γ-isosancapin nucleus structure, giving it unique biological activity. The compound has a LogP value of 3.0072, showing moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 49.33 Ų, indicating that the molecule has certain polar groups, which facilitate binding to biological macromolecule targets.

Low water solubility (0.0363 mg/mL) indicates that hydroxy-γ-isosancapanine has limited solubility in the aqueous phase, which may affect its bioavailability. Notably, this compound has a high ability to penetrate the blood-brain barrier, suggesting its potential role in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames mutagenic test results were 0.0, indicating hydroxy-γ-isosancaphantin had no obvious genotoxicity and good safety.

Plant Origins and Extraction Methods

Hydroxy-γ-isosancaphantin is mainly found in volatile oils and fat-soluble extracts of clove and horse chestnut clover. As a spice plant widely used in food seasoning and traditional medicine, clove's flower buds contain abundant volatile compounds and alkylamides. Horse chestnut clover has been widely studied for its diverse medicinal value, and its oil components also contain hydroxy-γ-isosanphyl.

The extraction method typically uses solvent extraction combined with chromatography separation technology. Common solvents include ethanol, ethyl acetate, and n-hexane. Select appropriate polar solvents based on their lipid solubility characteristics to improve extraction efficiency. The extraction process generally includes plant material crushing, solvent soaking, ultrasound-assisted extraction, or reflux extraction, followed by rotary evaporation concentration to obtain the crude extract. The purification steps mainly rely on column chromatography (such as silica gel columns, reversed-phase C18 columns) and high-performance liquid chromatography (HPLC) to obtain high-purity hydroxy-γ-isosancapacin.

In recent years, supercritical CO2 extraction technology has gradually been applied to extract these components due to its green environmental friendliness and efficient selectivity, significantly improving extraction purity and yield, while avoiding the problem of organic solvent residues.

Pharmacological activity research

The pharmacological activity of hydroxy-γ-isosanshaloshanshin mainly focuses on anti-inflammatory, analgesic, and neuromodulative effects. Its best-known physiological effect is inducing a localized numbness, a sensation closely related to its regulation of specific ion channels.

Anti-inflammatory activity

Numerous in vivo and in vitro experiments have shown that hydroxy-γ-isosancapanine has significant anti-inflammatory effects. It alleviates inflammatory responses by inhibiting the release and expression of various inflammatory mediators. Specifically, it reduces levels of pro-inflammatory cytokines such as IL-6 and TNF-α, and inhibits the activity of inflammation-related enzymes such as PTGS1 (COX-1), PTGS2 (COX-2), and NOS2 (induced nitric oxide synthase), thereby alleviating tissue inflammatory damage.

Analgesic effect

Hydroxy-γ-isosancapanine modulates pain receptors such as TRPV1 and TRPA1. TRPV1 (capsaicin receptor) and TRPA1 (aromatic hydrocarbon receptor) are important ion channels in sensory nerves, involved in the transmission of pain and inflammation signals. Hydroxy-γ-isosanyanyanin exhibits analgesic effects by regulating the activity of these channels and inhibiting pain signal transmission.

Neuroregulation

This compound has a high blood-brain barrier penetration ability, suggesting it may be involved in central nervous system regulation. Research shows that hydroxy-γ-isosancapanine regulates transcription factors such as STAT3 and NFKB1, which play key roles in neuroinflammation and neuroprotection, suggesting its potential application value in neurological diseases.

Mechanism of action and molecular targets

The pharmacological mechanism of hydroxy-γ-isosancapanine involves multiple signaling pathways and molecular targets, mainly focusing on inflammation regulation and neuroreceptor regulation.

Inflammation-related targets

• IL-6 (interleukin-6): Hydroxy-γ-isosancapanine can inhibit IL-6 expression and reduce inflammatory responses. IL-6 is a key mediator of various inflammatory and immune responses, and its overexpression is closely linked to multiple chronic inflammatory diseases.
• STAT3 (Signal Transduction and Transcription Activator 3): As a downstream transcription factor in the IL-6 signaling pathway, STAT3 regulates the expression of inflammatory genes. Hydroxy-γ-isosancapanine blocks inflammatory signaling by inhibiting STAT3 activation.
• CASP1 (Caspase 1): CASP1 is involved in the maturation and release of the pro-inflammatory cytokine IL-1β. The inhibitory effect of hydroxy-γ-isosancapanine on CASP1 helps alleviate inflammatory cascade reactions.
• PTGS1 and PTGS2 (cyclooxygenases 1 and 2): Hydroxy-γ-isosancapacin inhibits the activity of these two enzymes, reducing prostaglandin production and lowering inflammation and pain.
• TNF (tumor necrosis factor α): Hydroxy-γ-isosanphylin can inhibit the expression of TNF-α and reduce inflammatory responses.
• NOS2 (Induced Nitric Oxide Synthase): By inhibiting NOS2, it reduces the production of excess nitric oxide, preventing oxidative stress and inflammatory damage.
• NFKB1 (nuclear factor κB subunit 1): Hydroxy-γ-isosancaphanin blocks the NFKB signaling pathway, inhibits transcription of pro-inflammatory genes, and exerts anti-inflammatory effects.

Neuroreceptor targets

• TRPV1 (Transient Receptor Potential Vanillin Receptor 1): Hydroxy-γ-isosancaphanin regulates TRPV1 channel activity, affects calcium influx, and regulates pain and numbness.
• TRPA1 (Transient Receptor Potential Vanillic Acid Receptor-Related Channel 1): By modulating TRPA1, hydroxy-γ-isosancapanine participates in the regulation of chemical pain and inflammation perception.

In summary, hydroxy-γ-isosancapanine exerts its anti-inflammatory and analgesic pharmacological effects through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

Druggability analysis of hydroxy-γ-isosancapanine shows it has promising potential for drug development. The molecular weight of 289.4190 conforms to the Lipinski rule, and the LogP value of 3.0072 indicates moderate lipid solubility, which is beneficial for oral absorption and cell membrane penetration. TPSA is 49.33 Ų, supporting its excellent biofilm permeability.

Lower water solubility may limit oral bioavailability, but can be improved through formulation techniques such as nanocarriers and liposome encapsulation. Its high blood-brain barrier penetration ability offers possibilities for treating central nervous system diseases.

In terms of safety, the hERG channel has no inhibitory effects, reducing the risk of cardiotoxicity; The Ames test was negative, indicating no mutagenicity and relatively good safety.

Pharmacokinetic research is still in its early stages. Current literature reports that hydroxy-γ-isosancapanine has good distribution characteristics in the body, and its metabolic pathway mainly involves hepatic enzyme systems; its metabolites require further identification. Its half-life and clearance rate parameters still require systematic study.

Prospects and outlooks for clinical applications

Hydroxy-γ-isosancaparan, as a natural anti-inflammatory and analgesic active ingredient, has broad clinical application potential. Its multi-target mechanism of action makes it highly valuable in treating chronic inflammatory diseases (such as rheumatoid arthritis and inflammatory bowel disease), neuropathic pain, and neuroinflammatory diseases.

Future research should focus on:

1. Systematic review of pharmacokinetics and toxicology: clarify in vivo metabolic pathways, pharmacokinetic characteristics, and long-term safety.
2. Dosage Form Optimization: Solves poor water solubility, improves bioavailability, and develops formulations suitable for clinical applications.
3. Preclinical model validation: Using animal inflammation and pain models to further verify efficacy and mechanisms of action.
4. Clinical trial design: Conduct early-stage clinical studies to evaluate safety, tolerability, and preliminary efficacy.
5. Structural modification and derivative development: Based on the hydroxy-γ-isosancapacin structure, design derivatives with greater activity and superior pharmacokinetic properties.

Moreover, given its regulatory effects on TRPV1 and TRPA1 channels, the potential of hydroxy-γ-isosancapanine in neuromodulation is also worth further exploration, especially in the treatment of chronic pain and neurodegenerative diseases.

Conclusion

Hydroxy-γ-isosanyan, as an important alkylamide natural product in clove and horse chestnut oil, demonstrates promising pharmaceutical potential due to its unique chemical structure and significant anti-inflammatory and analgesic activities. Its multi-target and multi-mechanism mode of action provides a valuable example for pharmacological research of natural products. In the future, with the advancement of pharmacokinetics, toxicology, and clinical research, hydroxy-γ-isosancapanine is expected to become an important candidate for natural product drug development, driving innovation and application of natural anti-inflammatory drugs.

This review systematically summarizes the research progress of hydroxy-γ-isosancapatin, aiming to provide a theoretical foundation and reference for scientific research and drug development in related fields, and to promote its translational application in clinical treatment.