Product name: Zingiberensis saponin I
Synonym name:
Catalogue No.: BP3407
Cas No.: 91653-50-8
Formula: C₅₁H₈₂O₂₂
Mol Weight: 1047.2
Botanical Source:
Physical Description:
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
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

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

HPLC of Zingiberensis saponin I

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

Shield Leaf Glycoside: Molecular Analysis of Anti inflammatory Natural Saponins Derived from Dioscorea opposita

1. Overview

Zingiberensis saponin I is a natural steroidal saponin isolated from the traditional medicinal plant Dioscorea zingiberensis. Its CAS number is 91653-50-8, the molecular formula is C51H82O22, and the molecular weight is as high as 1047.2000 g/mol. It belongs to the complex structure of large molecule natural products. In the fields of natural product chemistry and drug discovery, steroidal saponins have attracted much attention due to their wide range of biological activities. As one of them, the research value of Dunye Xin Gan mainly focuses on its significant anti-inflammatory activity. Existing pharmacological studies have shown that it can intervene in the inflammatory signaling pathway by acting on multiple key inflammation related targets, such as TNF, PTGS2, NFKB1, IL6, and IL1B. Although the plant derived Dioscorea nipponica has long been used in traditional medicine, the systematic study of new saponins from Dioscorea nipponica as a single active ingredient, especially their precise molecular mechanisms and potential for medicinal development, remains a cutting-edge topic in modern natural medicine chemistry and pharmacology research. This article will provide a systematic professional interpretation of this compound from its chemical nature, origin, pharmacological mechanism, drug properties, and prospects.

2. Chemical structure and physicochemical properties

The molecular formula of Shield Leaf Glycoside is C51H82O22, with a molecular weight of 1047.2000 g/mol, and it is a typical steroid saponin compound. From its SMILES structural formula, it can be inferred that the core of its structure is the steroid mother nucleus (cyclopentane and phenanthrene structure), which is connected to multiple sugar groups (such as glucose) through glycosidic bonds, forming a complex sugar chain structure. The structural characteristics of these polyhydroxy and polysaccharide groups directly determine their physical and chemical properties.

According to the provided pharmacokinetic parameters, the logarithm of the lipid water partition coefficient (LogP) is 1.3896 and the LogD is 1.3894, indicating that the compound has a certain degree of lipophilicity under physiological pH conditions, but not highly lipophilic. Its topological polar surface area (TPSA) is as high as 335.0600 Å ², which is closely related to the presence of a large number of polar groups such as hydroxyl and ether bonds in its molecules. A high TPSA value usually indicates high molecular polarity and good water solubility, but limited transmembrane permeability. The calculated water solubility is 0.2269 mg/mL, belonging to the category of slight solubility, which is consistent with the expected portion of highly polar molecules. However, the complex structure may also lead to high crystal stacking energy, affecting the actual solubility.

The molecular weight far exceeds the limit of conventional small molecule drugs (500 Da), which poses the primary challenge for their oral absorption and bioavailability. Overall, Shield Leaf Glycoside is a highly polar and high molecular weight steroidal saponin, and its physicochemical properties lay the foundation for its subsequent biological activity and pharmacokinetic behavior.

3. Plant sources and traditional applications

The plant source of Dioscorea zingiberensis is Dioscorea zingiberensis C.H. Wright, commonly known as "yellow ginger", "fire vine root", etc. It is a perennial winding herbaceous plant of the Dioscoreaceae family and the Dioscorea genus. This plant is mainly distributed in the Yangtze River Basin and southern regions of China, such as Hubei, Sichuan, Shaanxi, and other places.

In traditional Chinese medicine practice, the rhizome of Dioscorea opposita (often referred to as "yellow ginger") has a long history of application. It is warm in nature, bitter and pungent in taste, and belongs to the liver and spleen meridians. Traditionally used for dispelling wind and dampness, promoting blood circulation and unblocking collaterals, reducing swelling and relieving pain. Commonly used for the treatment of rheumatism, joint discomfort, injuries from falls, abscesses, and other conditions. These efficacy descriptions are often related to "inflammation" and "pain", implying that they contain a substance basis for anti-inflammatory activity. Modern plant chemistry research has confirmed that Dioscorea opposita is rich in various steroidal saponins, which are considered the main carriers of its pharmacological activity. Dunyexin glycoside is one of the many active saponins isolated and identified from this plant. The traditional application experience has pointed out the direction for modern research, which is to search for effective anti-inflammatory and analgesic ingredients from this plant, and the discovery of shiitabine is the result of this approach.

4. Pharmacological activity and mechanism of action

The core pharmacological activity of Shield Leaf Glycoside is concentrated in anti-inflammatory Function. Its mechanism of action is not through a single target, but through the intervention of multiple targets and pathways in the complex inflammatory network. The existing target information suggests that it mainly acts on five key inflammatory mediators and signaling molecules: TNF, PTGS2, NFKB1, IL6, and IL1B.

1. Regulation of pro-inflammatory cytokines (TNF, IL6, IL1B)：

   • Tumor necrosis factor alpha (TNF - α) It is one of the earliest and most important core pro-inflammatory cytokines in the inflammatory response, which can activate multiple downstream signaling pathways and amplify the inflammatory response. Dunyexin glycoside may exert inhibitory effects at the initial stage of the inflammatory cascade by inhibiting the production of TNF - α or blocking its binding to receptors.
   • Interleukin-6 (IL-6) and interleukin-1 β (IL-1 β) They are two other key pro-inflammatory cytokines involved in processes such as fever, acute phase protein synthesis, and immune cell activation. They often work synergistically with TNF - α to form an inflammatory cytokine storm. The inhibitory effect of Shield Leaf Glycoside on IL6 and IL1B contributes to the comprehensive downregulation of excessive pro-inflammatory state.

2. Intervention on key inflammatory enzymes and signaling pathways (PTGS2, NFKB1)：

   • Prostaglandin endoperoxide synthase 2 (PTGS2, also known as COX-2) It is a key rate limiting enzyme that catalyzes the production of prostaglandins (PGs) from arachidonic acid, especially inducing high expression at the site of inflammation. The PGE2 produced is the main mediator leading to inflammation, pain, and fever. The inhibitory effect of Shield Leaf Glycoside on PTGS2 is similar to the mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs), but may be more selective (targeting inducible COX-2), thereby reducing the risk of gastrointestinal side effects caused by inhibition of constitutive COX-1.
   • Nuclear factor kappa B1 (NF - κ B1, also known as p50) It is a core member of the NF - κ B transcription factor family. The NF - κ B pathway is the master switch that regulates the expression of numerous inflammation related genes, including TNF - α, IL-6, IL-1 β, COX-2, etc. In the resting state, NF - κ B binds to the inhibitory protein I κ B and exists in the cytoplasm; When stimulated by TNF - α and other factors, I κ B is phosphorylated and degraded, allowing NF - κ B (such as p50/p65 dimer) to enter the nucleus and initiate gene transcription. The targeting effect of Shield Leaf Glycoside on NFKB1 may indicate that it can intervene in the activation or nuclear translocation process of NF - κ B, thereby extensively inhibiting the expression of downstream inflammatory mediators at the transcriptional level. This is one of the core mechanisms by which it exerts multi-target anti-inflammatory effects.

Integrated explanation of mechanism of action Shield leaf glycoside may inhibit the overactivation of the NF - κ B signaling pathway directly or indirectly. The downregulation of NF - κ B activity leads to a decrease in the expression of downstream target genes such as TNF - α, IL-6, IL-1 β, and COX-2. Meanwhile, it may also independently inhibit the activity of COX-2 enzyme. In this way, from the transmission of inflammatory signals (NF - κ B pathway), the production of inflammatory mediators (TNF - α, ILs) to the synthesis of final effector molecules (prostaglandins), Shield Leaf Glycosides achieve multi-level and multi-target synergistic inhibition, thereby exerting strong anti-inflammatory effects. This multi-target characteristic makes it potentially advantageous in the treatment of complex chronic inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and inflammatory bowel disease.

5. Evaluation of drug properties

Based on the provided pharmacological parameters and in combination with classic standards such as the Lipinski Rule of Five (Ro5), a preliminary evaluation of the pharmacological potential of Shield Leaf Glycoside can be conducted. The Lipinski rule is commonly used to predict the absorption and permeability of small molecule oral drugs, with core criteria being: molecular weight MW<500, LogP<5, number of hydrogen bond donors HBD<5, and number of hydrogen bond acceptors HBA<10.

• Molecular weight (MW)：1047.1950 Da， Far exceeding the 500 Da upper limit of Ro5. This is one of the biggest obstacles to its development as an oral drug, as large molecules often have difficulty crossing the intestinal epithelial cell membrane through passive diffusion.
• Fat solubility (LogP/LogD)Approximately 1.39, within the reasonable range of Ro5 (<5), but considering its high TPSA, its overall properties are more hydrophilic.
• Polarized surface area (TPSA)335.06 Å ², extremely high. It is generally believed that oral absorption of TPSA>140 Å ² is poor. A very high TPSA means that there are numerous hydrogen bonding sites on the molecular surface, which strongly bind water molecules and are not conducive to crossing lipid bilayer biofilms.
• Permeability and absorption：
  • Caco-2 permeability: 0.4241 (low value), the model simulating intestinal absorption shows poor permeability, consistent with predictions of high MW and high TPSA.
  • Effective permeability (Peff)0.4379, also in the low range, further confirms its difficulty in oral absorption.
  • Blood-brain barrier (BBB) penetrability Evaluated as' low '. This is unfavorable for the treatment of central nervous system diseases, but for their main anti-inflammatory indications (mostly peripheral inflammation), it may actually reduce central side effects, which is a beneficial characteristic.
• Protein binding rate (PPB)62.63%, belonging to the moderate level, means that more than one-third of the drugs in the blood exist in free form and can be distributed to tissues to exert their effects.
• Preliminary assessment of toxicity risk：
  • Genotoxicity The Ames test value is 0.3 (usually>1.0 is considered to have mutagenic risk), indicating a low risk in this testing system; Chromosome aberration test is' none '.
  • cardiotoxicity HERG inhibition is' no ', preliminarily ruling out the serious risk of QT interval prolongation and arrhythmia.
  • Hepatotoxicity The indicators of serum alkaline phosphatase (Ser_LK) and aspartate aminotransferase (Ser_ST) show "yes", indicating that changes in biomarkers related to liver function may be observed under experimental conditions, and close attention should be paid to their potential risk of liver injury. However, the values of γ - glutamyltransferase (Ser_GGT) and alanine aminotransferase (Ser_LT) are 'no', and the results need to be interpreted comprehensively.
  • Other toxicities Skin sensitization, respiratory sensitization, phototoxicity, etc. are all negative, and MRTD (maximum recommended therapeutic dose) evaluation is "no", which may indicate that the treatment window or safety range needs to be further determined.

Comprehensive evaluation conclusion As a lead compound, Shield Leaf Glycoside Advantage It lies in a clear, multi-target anti-inflammatory pharmacological mechanism and relatively low initial genetic toxicity and cardiac toxicity risk. However, it Significant pharmaceutical defects Due to its excessive molecular weight (violating Ro5) and extremely high polar surface area, its expected oral bioavailability is extremely low, making it difficult to administer through conventional oral routes. This determines that it is unlikely to be directly developed as a traditional small molecule oral drug.

Future development strategies may need to shift towards:
1. New drug delivery system Such as nano formulations (liposomes, polymer nanoparticles), prodrug strategies, or transdermal delivery systems to improve their absorption and delivery.
2. Injection administration Develop intravenous or local injection formulations to bypass absorption barriers and directly exert systemic or local anti-inflammatory effects.
3. Research on the mechanism of action It can serve as an excellent molecular probe for in-depth research on the anti-inflammatory signaling network of steroidal saponins, or as a structural template for rational analysis Simplification or modification of structure While retaining the pharmacophore, reduce molecular weight and polarity, and optimize the properties of the drug.

6. Research Status and Application Prospects

At present, research on the new glycoside of shield leaves is still in progress Preclinical stage Mainly focused on plant chemistry (extraction, isolation, structural identification), in vitro pharmacological activity screening, and preliminary mechanism of action exploration. Previous studies have confirmed its anti-inflammatory activity and effects on multiple inflammatory targets, but further details on signaling pathways, in vivo pharmacological validation (in animal disease models), comprehensive pharmacokinetics (absorption, distribution, metabolism, excretion), and toxicological evaluation are still insufficient.

Application Prospects Mainly reflected in the following aspects:

1. As a natural anti-inflammatory lead compound Its multi target action characteristics conform to the network pharmacology concept of modern treatment of complex inflammatory diseases (such as rheumatoid arthritis, atherosclerosis). Through structural optimization, it is expected to develop anti-inflammatory drugs with novel mechanisms of action.
2. Developed as a plant-based medicine or injection: In view of its poor oral absorption, it may be a faster transformation path to develop it directly as a traditional Chinese medicine injection or local topical preparation (such as gel or patch for arthritis treatment). This requires strict adherence to drug registration requirements and completion of systematic pharmaceutical, pharmacological, toxicological, and clinical research.
3. Functional food or cosmetic additives Under the premise of ensuring safety, dioscin or its extract from Dioscorea opposita, which is rich in this ingredient, can be used to develop health foods or high-end skincare products with anti-inflammatory and soothing functions.
4. Scientific research tools As specific steroidal saponin molecules, they can be used to study the interactions between such compounds and biological membranes and receptor proteins, enriching the research content of natural product chemistry and glycobiology.

Future research directions It should include: ① Using gene knockout/knockdown techniques, reporter gene systems, etc., to accurately elucidate the specific molecular links involved in their intervention in pathways such as NF - κ B at the cellular level; ② Establish a suitable animal model of inflammation and evaluate its in vivo efficacy and dose-response relationship; ③ Conduct systematic ADMET (absorption, distribution, metabolism, excretion, and toxicity) research to identify development bottlenecks and solutions; ④ Conduct in-depth structure-activity relationship research and obtain derivatives with better activity and drug properties through chemical synthesis or semi synthesis methods.

In summary, Shield Leaf Glycoside is a natural steroidal saponin with clear anti-inflammatory activity, and its multi-target mechanism of action endows it with unique value. Despite facing significant challenges in drug formulation, it is still expected to occupy a place in the prevention and treatment of inflammatory diseases in the future through innovative drug chemistry strategies and dosage form design, or at least provide valuable structural insights and biological understanding for the design of new generation anti-inflammatory drugs.