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Product name: Hydroxy-α-sanshool
Synonym name:
Catalogue No.: BP4106
Cas No.: 83883-10-7
Formula: C16H25NO2
Mol Weight: 263.381
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.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
Description:
Hydroxy-alpha-sanshool exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia. It also has analgesic properties, it activates TRPV1 and TRPA1 in sensory neurons.
References:
Biophysical Journal, 2012, 102(3):323a.
The Plant-Derived Alkylamide, Hydroxy-Alpha-Sanshool, Induces Analgesia through Inhibition of Voltage-Gated Sodium Channels
Many native cultures use extracts from Xanthozylum plants to topically treat toothache and joint pain. One active component of these extracts is the alkylamide, Hydroxy-alpha-sanshool, which induces tingling and numbing paresthesia when applied to the skin or tongue. To understand the physiological mechanisms underlying paresthesias, we sought to identify the molecular targets of sanshool in the somatosensory system.
METHODS AND RESULTS:
We first measured the analgesic properties of sanshool using mouse models of somatosensory behavior. Topical application of sanshool on the hind paw of naïve mice did not alter their sensitivity to noxious thermal or mechanical stimuli. However, in a model of neurogenic inflammation, sanshool acutely suppressed inflammatory hypersensitivity to mechanical force whereas it did not suppress hypersensitivity to heat. These data suggest that sanshool inhibits activity of a subset of sensory neurons that transduce mechanical, but not thermal, stimuli. In cultured dorsal root ganglion (DRG) neurons from mice, sanshool inhibited action potential (AP) firing in a subset of medium-to-large diameter neurons, which are thought to mediate mechanotransduction. In contrast, sanshool did not inhibit AP firing in small-diameter sensory neurons, which predominantly transduce noxious heat. In addition to size, sensory neurons are distinct in their expression of sensory neuron-specific voltage-gated sodium channels. Thus the differential effect of sanshool on sensory neurons may be due to selective activity of sanshool on different sodium channels. To test this idea, we compared the effects of sanshool on two sodium channel subtypes that are expressed in sensory neurons, Nav1.7 and 1.8. Sanshool reduced the magnitude of Nav1.7 and Nav1.8 currents but caused a hyperpolarizing shift in the steady-state inactivation curve of Nav1.7 only.
CONCLUSIONS:
Thus intrinsic molecular differences between sensory neurons, such as expression of different sodium channel subtypes, may underlie specificity of sanshool action.
HPLC of Hydroxy-α-sanshool
HNMR of Hydroxy-α-sanshool
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
49.3300
2.4863
2.4855
.1288
1.0942
16.1389
High
76.0528
3.2087
Yes
Yes
Yes
No
No
No
0.0
No
Yes
Yes
Yes
Hydroxy α-α-sanshool (CAS No.: 83883-10-7) is a natural product derived from plants of the genus Sanshool. Due to its unique chemical structure and remarkable biological activity, it has attracted widespread attention in pharmacological research in recent years. As an agonist of TRPA1 and TRPV1 receptors, hydroxy-α-sanshaloshantinol has shown significant value in research on pain regulation mechanisms. Moreover, increasing research indicates that this compound has potential therapeutic effects in the field of anti-tumor treatment, involving multiple tumor-related molecular targets. This paper will systematically review the chemical structure and physicochemical properties of hydroxy-α-sanshalin, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide a theoretical foundation and reference for in-depth research and drug development of this natural product.
Hydroxy-α-salatin belongs to the sanfusid class of compounds, with a molecular formula of C17H27NO2 and a molecular weight of 263.3810. Its structural features mainly include a hydroxyl-containing aliphamine backbone with certain polarity and hydrophobicity, a LogP value of 2.4863, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 49.33 Ų, suggesting moderate molecular polarity and possibly good bioavailability. Its low water solubility (0.1288 mg/mL) somewhat limits its direct oral absorption, but it also helps its stability and membrane binding ability in lipid environments.
The hydroxyl group in the hydroxy-α-sancapanine structure confers a certain degree of hydrophilicity, and this molecule does not inhibit the hERG channel, indicating a low cardiotoxicity risk. The Ames test result was 0, indicating that the compound showed no significant genotoxicity. Additionally, hydroxy-α-sanshalogen has a high blood-brain barrier penetration ability, suggesting its potential value in central nervous system (CNS) diseases.
Hydroxy-α-sancapin is mainly found in the fruits and rhizomes of plants of the genus Zanthoxylum spp., with particularly abundant content in Sichuan pepper (Zanthoxylum bungeanum) and Sichuan pepper (Zanthoxylum simulans). Plants of the Sichuan pepper genus are widely distributed across Asia, and in traditional Chinese medicine, they are often used in traditional Chinese medicine to dispel wind, relieve pain, promote blood circulation, and remove blood stasis.
The main extraction methods for hydroxy-α-sanshalosin include solvent extraction, ultrasound-assisted extraction, and liquid chromatography separation. Common solvents are ethanol or methanol, combined with ultrasound-assisted technology, which can improve extraction efficiency and purity. After rotary evaporation and concentration, the extract was separated and purified using column chromatography or high-performance liquid chromatography (HPLC), ultimately obtaining high-purity hydroxy-α-sanshaloscaphanin.
In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to the extraction of this compound, offering advantages such as fast extraction speed, low solvent residue, and environmental friendliness, providing a viable solution for industrial production.
The pharmacological activity of hydroxy-α-sanjiazine is mainly concentrated in the two major fields of neuromodulation and anti-tumor activity.
Hydroxy-α-sanmatin is an agonist of TRPA1 and TRPV1 in the TRP (Transient Receptor Potential) channel family, with EC50s of 69 μM and 1.1 μM, respectively. TRPV1 receptors are important targets for sensing heat pain and inflammatory pain, while TRPA1 receptors participate in the transmission of chemical and mechanical pain. Hydroxy-α-sanyanyanin activates these two receptors, inducing calcium ion influx and regulating neuronal excitability, thereby affecting pain perception and nerve conduction.
In animal models, hydroxy-α-sanshalogen exhibited significant analgesic effects, especially in inflammatory and neuropathic pain models, where it modulates TRP channel activity to alleviate pain behavior, suggesting its potential as an analgesic. Additionally, this compound has high penetration into the central nervous system and may be involved in central pain regulation.
Hydroxy-α-sanshalogen exhibits effects in various tumor cell lines that inhibit proliferation and induce apoptosis. Its antitumor mechanism involves multiple signaling pathways and key molecular targets, including:
These multi-target and multi-pathway mechanisms make hydroxy-α-sanshalogen a candidate molecule with broad-spectrum anti-tumor potential.
The biological effects of hydroxy-α-sanphylin are mainly realized through its activation of TRPA1 and TRPV1 receptors. TRP channels act as non-selective cation channels on cell membranes, regulating calcium ion influx and participating in various physiological processes such as pain, inflammation, and nerve conduction. Hydroxy-α-sanshalogen has a high affinity for TRPV1 (EC50 of 1.1 μM), enabling it to effectively activate this receptor, induce neuronal excitation, and trigger pain signaling.
In terms of antitumor effects, hydroxy-α-sanmanate achieves its biological effects by regulating multiple signaling pathways. Research shows that this compound can downregulate the expression of anti-apoptotic proteins MCL1 and BCL2, promoting tumor cells to enter the apoptosis program. At the same time, hydroxy-α-sanshalosin inhibits STAT3 phosphorylation, blocking its transcriptional activity, thereby suppressing tumor cell proliferation and immune escape. Additionally, hydroxy-α-sanshalosin reduces the matrix degradation and metastasis ability of tumor cells by inhibiting MMP2 activity.
Hydroxy-α-sanshalogen also affects DNA metabolism in tumor cells, inhibits TOP1 and TOP2A activities, interferes with DNA replication and repair, and leads to tumor cell cycle arrest and death. HIF1A inhibition limits tumor adaptability in hypoxic environments, suppressing angiogenesis and metabolic reprogramming. Regulation of the MAPK1 signaling pathway further affects the balance of cell proliferation and apoptosis. Regulation of hormone-related targets ESR1 and CYP19A1 provides new approaches for treating hormone-dependent tumors.
In summary, hydroxy-α-sanshalogen achieves complex pharmacological effects through the synergistic action of multiple targets and pathways, reflecting the diverse bioactivity characteristics of natural products.
The druggability parameters of hydroxy-α-sanshaloshanjin indicate that it has good potential for drug development. The molecular weight of 263.38 Da conforms to the Lipinski rule, with a LogP of 2.49, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. TPSA was 49.33 Ų, indicating good membrane permeability and bioavailability.
Its low water solubility (0.1288 mg/mL) may limit oral absorption, but solubility and bioavailability can be improved through formulation techniques such as nanoparticles and liposomes. Hydroxy-α-sanshaloshankan has a high blood-brain barrier penetration ability, making it suitable for treating central nervous system-related diseases.
In terms of safety, hydroxy-α-sanshalosin does not inhibit hERG channels, reducing the risk of cardiotoxicity; the Ames test was negative, indicating no significant genotoxicity. Additionally, preliminary pharmacokinetic studies show good stability and distribution characteristics in vivo, but the specific absorption, metabolism, and excretion (ADME) process still requires further systematic study.
Hydroxy-α-sanshaloshan, as an agonist of TRPA1 and TRPV1, has broad application prospects in pain management. Its unique mechanism of action provides a theoretical basis for developing novel analgesics, especially suitable for treating inflammatory and neuropathic pain. Moreover, its excellent blood-brain barrier penetration makes it potentially valuable for central pain and neurological diseases.
In the antitumor field, hydroxy-α-sanshalogen regulates tumor cell proliferation, apoptosis, and metastasis through multiple targets, demonstrating broad-spectrum anti-tumor activity. In the future, chemical modification and drug carrier technologies can be combined to optimize pharmacokinetics and targeting, enhancing clinical efficacy and safety. Especially in the treatment of hormone-dependent tumors, hypoxic microenvironment-related tumors, and drug-resistant tumors, hydroxy-α-sanshaloshanyanin holds significant application potential.
In addition, the multi-target properties of hydroxy-α-sanshalosin provide new research ideas for its application in inflammation, metabolic diseases, and other fields. In the future, molecular-level analysis of its mechanism of action should be strengthened, systematic pharmacokinetic and toxicological studies should be carried out, and its translation from the laboratory to clinical practice should be promoted.
Hydroxy-α-sanphylla, a natural product derived from plants of the genus Psiocla, has become a hot topic in natural product pharmacology research due to its unique chemical structure and diverse pharmacological activities. As TRPA1 and TRPV1 agonists, it plays a role in pain regulation, and in the field of antitumor therapy, it modulates multiple signaling pathways, demonstrating the advantages of natural products with multiple targets and mechanisms.
Druggability parameters indicate that hydroxy-α-sanshalogen has good potential for drug development and relatively high safety. In the future, by combining modern medicinal chemistry and formulation technologies, and deeply exploring its pharmacokinetics and clinical applications, hydroxy-α-sanjiaquin is expected to become an important candidate for novel analgesic and antitumor drugs.
In summary, hydroxy-α-sanshaloshanjin not only enriches pharmacological research on natural products but also provides new directions for drug development for related diseases, with broad prospects for research and application.
Shenshuai
Wenjing
Hedandan
