Product name: Tracheloside
Synonym name:
Catalogue No.: BP1401
Cas No.: 33464-71-0
Formula: C₂₇H₃₄O₁₂
Mol Weight: 550.557
Botanical Source: Trachelospermum jasminoides（Lindl.）Lem.
Physical Description:
Type of Compound: Lignans

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.

Description:

Tracheloside significantly decreases the activity of alkaline phosphatase (AP), an estrogen-inducible marker enzyme, with an IC(50) value of 0.31 microg/ml, a level of inhibition comparable to that of tamoxifen (IC(50) = 0.43 microg/ml).

References:

Biosci Biotechnol Biochem. 2006 Nov;70(11):2783-5.    

An anti-estrogenic lignan glycoside, tracheloside, from seeds of Carthamus tinctorius.    

The lignan glycoside, Tracheloside, was isolated from seeds of Carthamus tinctorius (Compositae) as an anti-estrogenic principle against cultured Ishikawa cells by employing a bioassay-linked HPLC-ELSD method. 

METHODS AND RESULTS:

Tracheloside significantly decreased the activity of alkaline phosphatase (AP), an estrogen-inducible marker enzyme, with an IC(50) value of 0.31 microg/ml, a level of inhibition comparable to that of tamoxifen (IC(50) = 0.43 microg/ml).    

Cancer Lett. 2003 Oct 28;200(2):133-9.    

Lack of significant inhibitory effects of a plant lignan tracheloside on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female Sprague-Dawley rats. 

Tracheloside, one of the plant lignans which can be extracted from the debris after safflower oil is produced from the seeds of Carthamus tinctorious, is an analogue of another plant lignan, arctiin, the side-chain C-2 of the five-membered ring being changed from a hydrogen to a hydroxyl group. We have already demonstrated that arctiin has chemopreventive effect on mammary carcinogenesis. Therefore, chemopreventive effects of Tracheloside on the initiation or post-initiation period of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female rats were examined. 

METHODS AND RESULTS:

For initiation, female Sprague-Dawley (SD) rats at the 6 weeks of age were given intragastric administrations of 100 mg/kg body weight of PhIP once a week for 8 weeks. The animals were treated with 0.2 or 0.02% Tracheloside during or after this carcinogen exposure. Control rats were fed basal diet with PhIP initiation or 0.2% Tracheloside or basal diet alone without initiation throughout the experimental period. All surviving animals were necropsied at the week 52 of administration. There were no clear treatment-related changes with statistical significance in all parameters for mammary carcinomas measured in this experiment. 

CONCLUSIONS:

These results indicate that Tracheloside may not exert significant effects on PhIP-induced mammary carcinogenesis at least under the present experiment condition.    

HPLC of Tracheloside

HNMR of Tracheloside

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

Introduction/Overview

Lignin compounds, as a type of natural product widely present in the plant kingdom, have always been a hot topic in natural medicinal chemistry and pharmacology research due to their structural diversity and extensive biological activity. Among them, Tracheloside (CAS number: 33464-71-0), as a lignin glycoside with unique pharmacological activity, has gradually attracted the attention of researchers in recent years. The initial research revealed its anti estrogenic activity, suggesting its potential application value in hormone related diseases. However, with the deepening of research, its pharmacological activity spectrum continues to expand, especially in promoting keratinocyte proliferation, accelerating wound healing, and exhibiting significant cardiovascular protective effects, showing multi-target and multi pathway characteristics. Luoshi glycoside promotes tissue repair by regulating key signaling pathways such as ERK1/2, and its multi-target mode of action involves multiple key molecules closely related to cardiovascular homeostasis, such as SELP, PPARG, ACE, AKT1, NOS3, providing a solid scientific basis for its application in the prevention and treatment of cardiovascular diseases. This article aims to provide a systematic review of the chemical structure, plant sources, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of luo shi glycoside, in order to provide comprehensive references for the in-depth development and transformation research of this natural product.

Chemical structure and physicochemical properties

Luoshi glycoside is a type of lignan glycoside compound. Its molecular formula is C27H34O12 and its molecular weight is 550.5570. Its basic structure consists of two phenylpropanoid units (C6-C3) connected by β - β 'to form a typical lignin skeleton, with one unit having a glycosidic group attached, which is the source of its "glycosidic" properties and significantly affects its water solubility and biological activity.

From the analysis of physical and chemical properties, the lipid water partition coefficient (LogP) of Luo Shi glycoside is 0.6260, indicating that it has a certain degree of lipophilicity, but overall tends to be hydrophilic. Its topological polar surface area (TPSA) is as high as 173.6000 Å ², mainly attributed to the numerous hydroxyl groups and oxygen atoms in the glycosidic structure of the molecule, which are potential hydrogen bond donors and acceptors. The higher TPSA value is consistent with the measured water solubility data (1.7200 mg/mL), indicating that quercetin has moderate solubility in aqueous media, which is beneficial for its absorption and distribution in organisms. Preliminary predictions of drug efficacy indicate that its ability to cross the blood-brain barrier is relatively low, suggesting that the risk of central nervous system related side effects may be relatively low. In addition, key toxicity warning indicators indicate that it has no inhibitory effect on hERG potassium channels (hERG inhibition: No), and the Ames test result is 0.0, preliminarily indicating that it is non mutagenic and has a relatively good safety basis.

Plant sources and extraction methods

Luoshi glycosides mainly come from plants in the Trachelossperm genus of the Apocynaceae family, which is also the origin of their name. Among them, the source plants that have been extensively studied include Trachelosspermum jasminoides (Lindl.) Lem. Its dried vine stems with leaves are often used in traditional medicine to dispel wind, unblock meridians, cool blood, and reduce swelling. In addition, this component has also been found in certain plants belonging to the same or other families.

Organic solvent extraction is commonly used to extract glycosides from plant materials. The common process includes heating reflux extraction or ultrasound assisted extraction of dried and crushed plant materials (such as Lonicera japonica) using polar solvents such as methanol or ethanol. The extract is concentrated under reduced pressure to obtain a crude extract. Subsequently, utilizing the polarity and solubility characteristics of the glycosides, a solvent (such as ethyl acetate, n-butanol, and water) was used for fractional extraction for preliminary enrichment. Further purification depends on column chromatography technology, which often uses silica gel, macroporous adsorption resin (such as D101), reverse silica gel (such as ODS) or dextran gel (such as Sephadex LH-20) and other fillers to perform gradient elution with chloroform methanol or methanol water solvent systems in different proportions. High performance liquid chromatography (HPLC), especially preparative HPLC, is the final key step in obtaining high-purity roscuronide monomers. Modern extraction techniques such as supercritical fluid extraction and microwave-assisted extraction also have potential applications, aimed at improving extraction efficiency and protecting thermosensitive components.

Pharmacological activity research

Luoshi glycoside exhibits diverse pharmacological activities, and its research has expanded from the initial single activity to multiple therapeutic fields.

1. Anti estrogen and skin repair activity Luoshi glycoside was early identified as an anti estrogenic substance. More importantly, research has found that it can effectively promote the proliferation of keratinocytes by stimulating the phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2). Keratinocytes are the main cells in the epidermal layer of the skin, and their proliferation and migration are the core processes of skin wound healing. Therefore, roscuronide has been proven to be a good active molecule that promotes wound healing, providing candidate compounds for the development of novel skin repair drugs or functional dressings.

2. Cardiovascular protective activity This is one of the most prominent fields in the pharmacological research of roscurogenin. Numerous in vitro and in vivo studies have shown that roscuronide has multiple protective effects on the cardiovascular system.

   • Anti atherosclerosis The expression of intercellular adhesion molecule-1 (ICAM1) and vascular cell adhesion molecule-1 (VCAM-1) in vascular endothelial cells induced by inflammatory factors can be significantly inhibited by complexoside, and the adhesion between monocytes and endothelial cells can be reduced, which is the initial key step of atherosclerosis.
   • Improve endothelial function It can upregulate the expression and activity of endothelial nitric oxide synthase (NOS3), promote the production of nitric oxide (NO), thereby relaxing blood vessels, inhibiting platelet aggregation and vascular smooth muscle cell proliferation.
   • Anti myocardial ischemia/reperfusion injury Research suggests that resveratrol may activate the AKT1 (protein kinase B) signaling pathway, inhibit myocardial cell apoptosis, alleviate oxidative stress, and protect against myocardial ischemia-reperfusion injury.
   • Regulating metabolism and blood pressure Its target involves peroxisome proliferator activated receptor gamma (PPARG), which is closely related to the regulation of glucose and lipid metabolism; Meanwhile, its potential role in angiotensin converting enzyme (ACE) suggests its possible involvement in blood pressure regulation.
   • Antithrombotic and cardiac electrophysiology By affecting P-selectin (SELP), it may intervene in platelet activation and thrombus formation. It has no direct inhibitory effect on potassium ion channels (such as the hERG channel encoded by KCNH2), reducing the risk of cardiac toxicity induced by tip twisting ventricular tachycardia.

3. Other potential activities Based on its multi-target properties, there have been research reports on the anti-inflammatory, antioxidant, and neuroprotective effects of roscuronide, but its specific effects and status still require more evidence to support.

Mechanism of action and molecular targets

The multiple pharmacological effects of Losartan, especially its cardiovascular protective effect, rely on a complex multi-target network rather than a single pathway.

1. Anti inflammatory and anti adhesive mechanisms In the vascular endothelial inflammation model, one of the core functions of resveratrol is to inhibit the activation of inflammatory signaling pathways such as nuclear factor kappa B (NF - κ B), thereby downregulating the transcription and expression of downstream effector molecules ICAM1 and VCAM1. At the same time, it also inhibits the expression of SELP on the surface of platelets and endothelial cells, blocks the rolling, adhesion and migration of leukocytes to the vascular intima from multiple links, and fundamentally fights atherosclerosis.

2. Endothelial protection and vasodilation mechanism Rhodiola rosea phosphorylates and activates the PI3K/AKT1 pathway, which in turn phosphorylates and activates NOS3, increasing the production of biologically active NO. NO is the most important endothelial derived relaxing factor in the body, and its elevated levels directly improve endothelial function, combat hypertension and arteriosclerosis.

3. Cell survival and anti apoptotic mechanism In models of myocardial or endothelial cell injury, the AKT1 signaling pathway activated by resveratrol plays a central role in promoting survival. AKT1 phosphorylates and inhibits various pro apoptotic proteins such as Bad and Caspase-9, while regulating pathways such as mTOR to promote the synthesis of cell survival proteins, effectively resisting cell apoptosis induced by hypoxia, oxidative stress, and other factors.

4. Metabolic and Hormonal Regulation Mechanisms As a potential regulator of PPARG, resveratrol may affect adipocyte differentiation, glucose uptake, and insulin sensitivity, providing clues for its application in metabolic syndrome related cardiovascular diseases. Its anti estrogenic activity may be achieved by competitively binding to estrogen receptors and regulating the expression of related genes.

5. Mechanism of wound healing In terms of skin repair, rosmarin rapidly activates the ERK1/2 MAPK signaling pathway, which transmits proliferation signals from cell membrane receptors to the nucleus, promotes the expression of cyclin in keratinocytes, drives cells from G1 phase to S phase, and accelerates cell proliferation and re epithelialization process.

In summary, the mechanism map of action of Luo Shi Glycosides covers multiple levels, including cell surface adhesion molecules (ICAM1, VCAM1, SELP), intracellular key kinases (AKT1, ERK1/2), metabolic nuclear receptors (PPARG), and key enzymes (ACE, NOS3), forming a synergistic network.

Evaluation of drug properties and pharmacokinetics

Based on the given parameters and existing research, a preliminary evaluation of the pharmacological properties of roscuronide is conducted

• Absorption and distribution Molecular weight 550.5570, belonging to medium-sized molecules. A LogP value of 0.626 and a high TPSA (173.6) indicate that it meets multiple criteria in the "Five Rules for Drug Analogy", but high TPSA may affect its passive transmembrane diffusion, and its oral bioavailability needs to be experimentally confirmed. Predicting low blood-brain barrier permeability is beneficial for concentrating on the peripheral system and reducing central side effects.
• Metabolism and excretion As a glycoside compound, roscuronide is likely to be first hydrolyzed by glycosidases in gut microbiota or epithelial cells in the body, producing aglycones (roscuronides) and glycosides. The enhanced lipid solubility of aglycones may make them more easily absorbed, but their metabolic pathways (such as phase I and phase II metabolism), major metabolites, and excretion pathways (bile/urine) still require detailed in vivo pharmacokinetic studies.
• Preliminary Safety Assessment The data shows that it does not inhibit the hERG channel, which is a very favorable safety feature and significantly reduces the potential risk of cardiac toxicity. The negative result of Ames test preliminarily ruled out the risk of genetic toxicity. However, comprehensive preclinical safety evaluation, including acute toxicity, long-term toxicity, reproductive toxicity, etc., is still an indispensable link in its conversion to drugs.
• Formulation considerations Among them, water solubility provides the possibility for the development of injectable or oral liquid formulations, but it may also require further improvement of solubility and stability through techniques such as salt formation, cyclodextrin inclusion, or nanoformulation to optimize the drug delivery effect.

At present, there are still few reports on the pharmacokinetic studies of the Luo Shi glycoside system, such as absolute bioavailability, half-life, tissue distribution, protein binding rate, etc. This is a key data gap that must be filled in future development.

Clinical application prospects and prospects

The multi-target pharmacological properties of Luo Shi glycoside have depicted broad prospects for its application in multiple clinical fields, but also face challenges.

1. Application Prospects：

   • Prevention and treatment of cardiovascular diseases This is the most promising direction. Atractoside can be used for the prevention and auxiliary treatment of atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, diabetes vascular complications, etc. It has the functions of anti-inflammatory, improving endothelial function, anti apoptosis, and potential metabolic regulation, which is in line with the modern treatment concept of multifactorial intervention for cardiovascular diseases.
   • Treatment of chronic difficult to heal wounds: Based on its clear role in promoting the proliferation of keratinocytes, it can be developed as a new type of wound healing promoter for diabetes foot ulcers, pressure ulcers, burns, poor wound healing and other clinical thorny problems. It can be made into gel, spray, dressing and other external dosage forms.
   • Hormone related diseases Its anti estrogen activity may have some value in the adjuvant treatment or prevention of breast cancer (especially estrogen receptor positive type), but it needs extremely careful evaluation and in-depth research.
   • As a lead compound The structure of its lignan glycoside can serve as a template for pharmaceutical chemical optimization, improving its pharmacokinetic properties (such as increasing oral bioavailability, prolonging half-life) or enhancing selectivity towards specific targets through structural modification, leading to the development of more clinically advantageous derivatives.

2. Challenges and Prospects：

   • Deep analysis of the mechanism of action At present, the understanding of the target of action of roscuronide is mostly based on bioinformatics prediction and preliminary verification, and more direct experiments (such as SPR, CETSA), gene knockout/knockdown techniques, etc. are needed to clarify the precise regulatory relationship between its direct target and upstream and downstream signal networks.
   • Systematic pharmacokinetic study Urgent need to carry out standardized animal and human (future) pharmacokinetic studies, clarify their ADME (absorption, distribution, metabolism, excretion) characteristics, and provide a basis for dosage form design and administration plan formulation.
   • Preclinical and clinical research It is necessary to complete a complete preclinical safety evaluation under GLP standards and gradually advance clinical trials to confirm its effectiveness and safety in humans.
   • Resources and Sustainability Direct extraction from plants has limited yield and requires the development of artificial cultivation or exploration of alternative production pathways such as chemical synthesis and synthetic biology (such as microbial heterologous synthesis) to meet the needs of future large-scale applications.

Conclusion

Luoshi glycoside, as a natural lignan glycoside derived from traditional medicinal plants, has shown significant development value in the fields of cardiovascular protection and skin wound repair due to its unique chemical structure and multi-target, multi pathway pharmacological mechanisms. The research process from anti estrogenic activity to promoting wound healing, and then to systemic cardiovascular protection, reflects the scientific development path of natural products from single activity discovery to complex mechanism interpretation. Although there are still many challenges in system pharmacokinetics, in-depth mechanism of action analysis, and clinical translation, existing research has laid a solid theoretical foundation for it. In the future, through interdisciplinary collaboration and modern drug research and development technology, Luo Shi Glycoside is expected to be successfully transformed from a potential natural active molecule into innovative drugs or functional products for the prevention and treatment of cardiovascular diseases and the promotion of tissue repair, contributing its unique value to human health.