Product name: Ziyuglycoside I
Synonym name: Kudinoside H; Gouguside 7
Catalogue No.: BP1467
Cas No.: 35286-58-9
Formula: C₄₁H₆₆O₁₃
Mol Weight: 766.966
Botanical Source: Ilex cornuta and Ilex kudincha
Physical Description: White powder
Type of Compound: Triterpenoids

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, up to kilograms
Inquire for bulk scale.

Descriptions:
Ziyuglycoside I, isolated from S. officinalis root extract, has anti-wrinkle activity, could be used as an active ingredient for cosmetics.[1]

References:
[1] Kim Y H, Chung C B, Kim J G, et al. Biosci Biotech Bioch, 2008, 72(2):303-11.
[2] Xie J B ,Bi Z M, Li P. Pharmaceutical Journal, 2003, 38(07):534-6.

HPLC of Ziyuglycoside I

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

Introduction/Overview

Natural products have long been an important source of drug discovery and development, particularly in the fields of anti-tumor, anti-inflammatory, and skin health. Ziyuglycoside I (CAS number: 35286-58-9) is a traditional medicinal plant derived from the Chinese elm tree（Sanguisorba officinalis L. The triterpenoid saponins isolated from roots have attracted much attention in recent years due to their diverse biological activities. Early research revealed its potential application in the cosmetics field, mainly manifested in significant anti wrinkle activity and the ability to promote the expression of type I collagen. With the deepening of research, Sanguisorba officinalis saponin I has been found to show strong pharmacological effects in anti inflammation, inducing tumor cell apoptosis and other aspects, especially in the treatment of triple negative breast cancer (TNBC) and other refractory diseases. Its mechanism of action involves the regulation of the p53 signaling pathway and the regulation of multiple key inflammatory and tumor related targets, such as interleukin-6 (IL-6), signal transduction and transcription activator 3 (STAT3), and nuclear factor kappa B (NF - κ B). This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of Diyu saponin I, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of Diyu saponin I is C41H66O13, with a molecular weight of 766.9660 Da. Its chemical structure belongs to pentacyclic triterpenoid saponins, and its aglycone is an Oleanane type triterpenoid, with sugar chains connected at positions C-3 and C-28, respectively. Typical glycosylation compositions include glucose, arabinose, etc., and this specific glycosylation modification has a decisive impact on their biological activity and water solubility.

According to the analysis of the parameters related to drug properties, the lipid water partition coefficient (LogP) of Diyu saponin I is 2.6332, indicating that it has a certain degree of lipophilicity, but not high hydrophobicity. Its topological polar surface area (TPSA) is as high as 215.8300 Å ², mainly attributed to multiple hydroxyl groups and oxygen atoms on the sugar ring in the molecule, indicating strong molecular polarity. The water solubility value is 0.0330 mg/mL, belonging to the category of slight solubility, which is consistent with its saponin structural characteristics, that is, it has both hydrophilic (glycosyl) and lipophilic (triterpenoid glycoside) parts. These physical and chemical properties determine its absorption and distribution characteristics in living organisms. For example, higher TPSA and molecular weight may pose challenges to its oral bioavailability. In addition, the predicted data shows that its ability to cross the blood-brain barrier is low, which limits its direct effect on central nervous system diseases, but may also reduce the potential risk of neurotoxicity. In terms of preliminary safety prediction, Diyu saponin I did not show hERG potassium channel inhibitory activity (low risk of arrhythmia), and the Ames test predicted a value of 0.0, suggesting that it may not have direct genetic toxicity.

Plant sources and extraction methods

Diyu saponin I mainly comes from the plant Diyu in the Rosaceae family, genus Diyu（Sanguisorba officinalis L. Dry roots. As a traditional Chinese medicine, Eucommia ulmoides has the effects of cooling blood, stopping bleeding, detoxifying and healing sores. Its chemical composition is complex, and in addition to Eucommia ulmoides saponin I, it also contains various active ingredients such as Eucommia ulmoides saponin II, tannins, flavonoids, etc.

The extraction of saponins I from plant materials is usually carried out using solvent extraction combined with modern separation and purification techniques. The standard procedure is as follows:
1. Preprocessing and Extraction After drying and crushing the roots of Eucommia ulmoides, methanol, ethanol, or ethanol water mixed solvents are often used for reflux extraction or ultrasound assisted extraction. The alcohol extraction method can effectively dissolve saponin components.
2. Preliminary enrichment After the extraction solution is concentrated under reduced pressure, the obtained extract can be suspended in water and then extracted sequentially with organic solvents such as petroleum ether and ethyl acetate to remove fat soluble impurities and some moderately polar components. Diyu saponin I mainly exists in the subsequent n-butanol extraction site or water layer (enriched by macroporous adsorption resin treatment).
3. Separation and Purification: The parts enriched in saponins are further separated by column chromatography, and commonly used fillers include silica gel, reverse silica gel (such as ODS), dextran gel (Sephadex LH-20), etc. By gradient elution using chloroform methanol water or methanol water systems with different ratios, combined with thin-layer chromatography (TLC) or high-performance liquid chromatography (HPLC) monitoring, the monomer compounds are gradually separated.
4. appraisal The final purified Diyu saponin I needs to be structurally confirmed by spectroscopic techniques such as nuclear magnetic resonance (NMR, including 1H-NMR, 13C-NMR, 2D-NMR), mass spectrometry (MS), and infrared spectroscopy (IR). High performance liquid chromatography-mass spectrometry (HPLC-MS) is also commonly used for qualitative and quantitative analysis of this component during the extraction process.

Optimizing the extraction process (such as solvent ratio, temperature, time) and adopting new preparation techniques such as high-speed countercurrent chromatography can help improve the extraction efficiency and purity of Diyu saponin I.

Pharmacological activity research

The pharmacological activity research of Diyu saponin I has expanded from the initial field of skin care to multiple biomedical fields such as anti-tumor and anti-inflammatory, demonstrating multifaceted therapeutic potential.

1. Skin protection and anti wrinkle activity This is one of the earliest discovered activities of Diyu saponin I. Research has confirmed that saponins from Eucommia ulmoides can significantly promote the synthesis of type I collagen in human skin fibroblasts. Type I collagen is the main structural protein of the dermis layer of the skin, and its reduced content and structural damage are key factors in skin aging and wrinkle formation. Diyu saponin I enhances skin elasticity by upregulating collagen gene expression, thereby exerting anti wrinkle and anti-aging effects, making it a highly promising active ingredient in functional cosmetics.

2. Antitumor activity Sanguisorba officinalis saponin I can inhibit proliferation and induce apoptosis of many tumor cells, especially in the study of triple negative breast cancer (TNBC). TNBC lacks estrogen receptor, progesterone receptor, and HER2 expression, resulting in limited treatment options and poor prognosis. Experiments have shown that saponins I from Eucommia ulmoides can effectively inhibit the vitality of TNBC cells (such as MDA-MB-231 cells), and its mechanism is closely related to the activation of tumor suppressor protein p53, which leads to cell cycle arrest (such as G1 phase arrest) and the initiation of mitochondrial dependent apoptosis pathway. In addition, it has also shown certain anti-tumor effects on other types of cancer such as liver cancer, colon cancer, etc.

3. anti-inflammatory activity Diyu saponin I has a wide range of anti-inflammatory effects. In macrophage or animal inflammation models induced by inflammatory stimuli such as lipopolysaccharides (LPS), saponins I from Eucommia ulmoides can significantly inhibit the excessive production of pro-inflammatory mediators. These mediators include nitric oxide (NO, induced by NOS2), prostaglandin E2 (PGE2, involved in PTGS1/COX-1 and PTGS2/COX-2), tumor necrosis factor - α (TNF - α), and interleukin-6 (IL-6). Its anti-inflammatory effect has been validated in animal models such as acute lung injury and colitis, indicating its potential value in treating diseases related to excessive inflammatory response.

4. Other activities Some studies also suggest that saponins from Eucommia ulmoides may have auxiliary activities such as antioxidant and antibacterial properties, which complement their anti-inflammatory and tissue repair promoting effects.

Mechanism of action and molecular targets

The multiple pharmacological activities of Diyu saponin I stem from its regulation of multiple key signaling pathways within cells, and its mechanism of action is complex, involving the following core targets and pathways:

1. P53 dependent cell cycle and apoptosis pathway (core anti-tumor mechanism)In tumor cells, dioscin I can stabilize and activate p53 protein. As the "guardian of the genome", p53 upregulates the expression of cyclin dependent kinase inhibitors (CDKI) such as p21 upon activation, leading to cell cycle arrest (such as in G1 phase) and preventing cell proliferation; On the other hand, p53 can promote the expression of pro apoptotic proteins (such as Bax, PUMA) and inhibit the function of anti apoptotic proteins (such as Bcl-2), leading to increased mitochondrial outer membrane permeability, release of cytochrome c, and activation of caspase cascade reactions (such as CASP3), ultimately executing the cell apoptosis program. This is an important molecular basis for its resistance to triple negative breast cancer and other p53 wild-type or functional recoverable tumors.

2. NF - κ B and STAT3 inflammatory signaling pathway (anti-inflammatory core mechanism)：

   • NF - κ B pathway NF - κ B is a core transcription factor that regulates the expression of inflammatory genes. Diyu saponin I can inhibit the activity of I κ B kinase (IKK), prevent the phosphorylation and degradation of I κ B protein, thereby causing NF - κ B (mainly composed of p50/p65 dimer) to remain in the cytoplasm and unable to enter the nucleus to initiate the transcription of many pro-inflammatory cytokines and enzyme genes such as IL-6, TNF, NOS2, PTGS2, etc.
   • STAT3 pathway STAT3 is another important pro-inflammatory and pro cancer signaling hub. After binding to receptors, cytokines such as IL-6 activate JAK kinase, leading to STAT3 phosphorylation, dimerization, and translocation into the nucleus. Diyu saponin I can inhibit the production of upstream IL-6 or directly interfere with the JAK/STAT3 phosphorylation process, block STAT3 signaling, and thus inhibit its mediated inflammatory response and tumor cell survival and proliferation.

3. Other related targets：

   • Cyclooxygenase (PTGS1/COX-1 and PTGS2/COX-2)Diyu saponin I can inhibit the expression and activity of COX-2 and reduce the production of inflammatory mediator PGE2.
   • Inflammatory bodies and CASP1 There are studies suggesting that it may inhibit the activation of NLRP3 inflammasome, reduce the activation of caspase-1 (CASP1), and thus inhibit the release of mature inflammatory factors such as IL-1 β.
   • Ion channels (TRPV1, TRPA1)These channels are involved in pain and neurogenic inflammation. Diyu saponin I may exert analgesic and anti neuroinflammatory effects by regulating the activity of these channels.
   • TNF signal Reduce inflammatory damage by inhibiting the production of TNF - α or interfering with its downstream signals.

In summary, the action of Diyu saponin I through multiple targets and pathways forms a synergistic anti-inflammatory and anti-tumor network, which provides advantages for its treatment of complex diseases.

Evaluation of drug properties and pharmacokinetics

Although dioscin I has shown good biological activity in vitro and some animal models, its drug like and pharmacokinetic (PK) properties are the key factors determining its successful development as a drug.

1. Analysis of drug properties parameters As mentioned earlier, the molecular weight of Diyu saponin I is close to 767, exceeding the standard of 500 in the Rule of Five; The TPSA value is relatively high (>140 Å ²). These parameters indicate the possibility of poor oral absorption and low bioavailability. Its slightly soluble properties may also affect formulation development and in vivo absorption. However, its LogP value is within the ideal range and there is no hERG inhibition or genotoxicity warning, which has certain advantages in terms of safety starting point.

2. Current status of pharmacokinetic research At present, there are relatively limited reports on the pharmacokinetic studies of the Diyu saponin I system, which is usually a bottleneck stage for the clinical development of natural product monomers. Based on its saponin structure, possible PK characteristics can be inferred:

   • absorb After oral administration, hydrolysis may occur in the gastrointestinal tract due to the action of acids, enzymes, and gut microbiota (removing some glycosides), converting them into secondary glycosides or aglycones. The absorption of these metabolites may be better than that of the prototype drug. The prototype drug itself may have poor passive diffusion absorption due to polarity and molecular weight issues.
   • distribution Predict low blood-brain barrier permeability, mainly distributed in the blood and peripheral tissues. The binding rate between it and plasma proteins is not yet clear and needs to be experimentally determined.
   • Metabolism The liver may be its main metabolic site, involved in phase I (such as CYP450 enzyme catalyzed redox) and phase II (such as glucuronic acid binding, sulfation) metabolic reactions. The structure of the sugar moiety may also make it a substrate for certain glycosidases.
   • excretion The prototype drug and its metabolites may be mainly excreted through bile and kidneys.

3. Formulation strategy and structural optimization In order to improve the pharmacological properties of Diyu saponin I, future research may consider:

   • New drug delivery system Develop formulation technologies such as nanoparticles, liposomes, microemulsions, and solid dispersions to improve their solubility and oral bioavailability, or develop transdermal drug delivery formulations for skin related indications.
   • Prodrug design By chemical modification (such as esterification, preparation of more easily absorbable prodrugs), their lipid solubility and membrane permeability are improved, and then converted into active forms in vivo.
   • Simplification of structure and screening of analogues On the basis of clarifying the pharmacophore, synthesize derivatives or analogues with simpler structures and better physicochemical properties, and conduct structure-activity relationship studies.

Comprehensive in vivo pharmacokinetics, tissue distribution, excretion studies, and toxicological evaluations (acute toxicity, chronic toxicity, reproductive toxicity, etc.) are necessary steps to advance its preclinical development.

Clinical application prospects and prospects

The diverse biological activities of Diyu saponin I have brought broad clinical application prospects in multiple therapeutic fields, but also face challenges.

1. Potential application areas：

   • Tumor therapy adjuvant drugs or candidate drugs Especially in the treatment of triple negative breast cancer, Sanguisorba officinalis saponin I induces apoptosis by activating the p53 pathway, which provides a new strategic idea for this kind of refractory breast cancer lacking targets. It is possible to explore its combination application with chemotherapy drugs to enhance efficacy or reduce chemotherapy dosage and side effects. It also has potential value for other malignant tumors with normal p53 function.
   • Treatment of inflammatory diseases Suitable for chronic or acute inflammatory diseases driven by excessive activation of pathways such as NF - κ B and STAT3, such as rheumatoid arthritis, inflammatory bowel disease (such as ulcerative colitis), acute lung injury, dermatitis, etc. Its multi-target anti-inflammatory properties may have more regulatory advantages than single target drugs.
   • Medical skincare products and dermatological medications As an active ingredient with clear efficacy, it is used in cosmetics, medical dressings or topical drugs for anti-aging, anti wrinkle, promoting wound healing and repairing skin barriers.
   • pain management By acting on channels such as TRPV1/TRPA1, it is possible to develop topical formulations for the treatment of neuropathic pain or inflammatory pain.

2. challenges faced：

   • Drug resistance and PK bottleneck As mentioned earlier, its large molecular weight and polarity may lead to low oral bioavailability, which is the main obstacle to its development as a systemic drug.
   • Depth and selectivity of mechanism of action Although it is known to act on multiple targets, further research is needed to determine the binding affinity, precise mode of action, and dominant mechanisms in complex disease networks for each target. Attention should also be paid to the unexpected side effects that may arise from its multi-target nature.
   • Natural source restrictions The cost of extracting and isolating from plants is relatively high, and the content is affected by factors such as place of origin and season. We need to develop sustainable supply methods, such as chemical total synthesis, semi synthesis, or biosynthesis (synthetic biology).
   • Complete preclinical and clinical data missing At present, most research is still at the stage of cell and animal models, lacking comprehensive preclinical safety evaluations (GLP toxicology) and human clinical trial data that comply with new drug development standards.

3. Future research directions：

   • Strengthen the research on precise mechanisms based on targets and the integration analysis of signal networks.
   • Focus on solving delivery problems and optimize its PK/PD characteristics using advanced drug delivery technology.
   • Conduct systematic preclinical development research, including comprehensive assessment of ADMET (absorption, distribution, metabolism, excretion, and toxicity).
   • Explore its use as a "drug lead compound" for structural modification and optimization to obtain derivatives with greater potential for development.
   • Consider developing it as one of the core quality markers for compound traditional Chinese medicine or herbal medicine, leveraging the advantages of holistic treatment with traditional Chinese medicine.

Conclusion

Diyu saponin I, as an active triterpenoid saponin derived from traditional Chinese medicine Diyu, has become a highlight molecule connecting traditional medicine and modern life science research due to its multiple pharmacological effects such as promoting collagen synthesis, anti-inflammatory, and inducing tumor cell apoptosis. Its potential in skin health, anti-tumor (especially triple negative breast cancer) and anti-inflammatory treatment is remarkable. The study of its mechanism of action revealed its multi-target characteristics by regulating key pathways such as p53, NF - κ B, STAT3, etc. However, the potential challenges of drug formation caused by its large molecular weight, high polarity, and other physicochemical properties, especially the issue of oral bioavailability, are the core challenges that must be overcome in future translational research. Through interdisciplinary strategies such as modern medicinal chemistry, pharmacy, and systems biology, in-depth exploration of its structural optimization, novel delivery systems, and complete preclinical development paths is expected to promote the gradual development of Diyu Saponin I from a promising natural active ingredient into a new drug or high-end efficacy product that can be used for clinical treatment, providing new choices for patients with related diseases and further interpreting the scientific connotation of modernization and internationalization of traditional Chinese medicine.