Product name: Ternatumoside II
Synonym name:
Catalogue No.: BP4614
Cas No.: 1473419-87-2
Formula: C₂₇H₃₀O₁₅
Mol Weight: 594.522
Botanical Source:
Type of Compound: Flavonoids

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.

HPLC of Ternatumoside II

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

Introduction/Overview

Flavonoids, as one of the largest and most biologically active families of natural products, are widely distributed in the plant kingdom and have long been of great concern due to their diverse pharmacological activities. Kaempferol, as a common flavonol glycoside, often exhibits enhanced bioavailability and unique biological activity in its glycosylated derivatives. Ternatumoside II (CAS number: 1473419-87-2) is one of its members, which is a novel flavonoid glycoside. In its molecular structure, the kaempferol glycoside is connected to a disaccharide chain composed of glucose and rhamnose through a hydroxyl group at position 3. This compound was initially isolated from the medicinal plant R. crenulata, and preliminary studies have revealed its significant immunomodulatory and antioxidant activities, particularly its ability to stimulate interferon - γ (IFN - γ) expression, making it potentially valuable in the fields of anti-inflammatory, antiviral, and immune related disease treatment. Meanwhile, its clear free radical scavenging ability suggests its potential in combating oxidative stress-related diseases such as neurodegenerative and cardiovascular diseases. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, medicinal properties, and clinical application prospects of Ternatumosis II, in order to provide comprehensive scientific references for the in-depth research and development of this natural product.

Chemical structure and physicochemical properties

The molecular formula of Ternatumoside II is C27H30O15, with a molecular weight of 594.5220. Its core structure is Kaempferol (4 ′, 5,7-trihydroxyflavonol) glycoside. Unlike many flavonol glycosides, glycosylation occurs on the 3-hydroxyl group of the aglycone, connected by a disaccharide chain. This disaccharide chain is composed of one molecule of β - D-glucose and one molecule of α - L-rhamnose connected by glycosidic bonds. Usually, the end of glucose is connected to rhamnose to form structures such as Rutinose or Neohesperidose. The specific connection method needs to be accurately identified by spectroscopic techniques such as nuclear magnetic resonance, but the name "glucose rhamnose" suggests its disaccharide composition.

Its physical and chemical properties are closely related to its structure. The logarithm of the calculated lipid water partition coefficient (LogP) is -0.3638, indicating that the compound has strong hydrophilicity, which is consistent with the presence of multiple hydroxyl and sugar groups on the molecule. The topologically polar surface area (TPSA) is as high as 249.2000 Å ², further confirming its high polarity characteristics, which affect its transmembrane permeability. The theoretically calculated water solubility value is 2.9215 (usually measured in mg/mL or logS, indicating moderate to high solubility), indicating good solubility in aqueous media, which is beneficial for formulation development. However, high polarity and large TPSA also result in a predicted "low" blood-brain barrier (BBB) permeability, meaning it may be difficult to enter the central nervous system through passive diffusion. In addition, preliminary pharmacological screening showed no inhibitory activity on hERG potassium channels (hERG inhibition: no), indicating a low potential risk of cardiac toxicity; The Ames test result is 1.2 (usually a value close to 1 indicates no mutagenicity), preliminarily indicating no genetic toxicity risk. These physicochemical and early safety parameters laid the foundation for its subsequent research.

Plant sources and extraction methods

The main plant source currently reported for Ternatumosis II is the Chinese cabbage genus in the family Saxifragaceae R. crenulata(usually referring to thick leaved rock cabbage or similar species). Chinese cabbage plants are commonly used in traditional medicine to treat cough, bronchitis, and inflammatory diseases, and their active ingredients are based on various phenolic compounds including flavonoid glycosides.

The extraction and separation of Ternatumoside II from plant materials usually follow the conventional process of natural product chemistry, but optimization is needed for its polarity characteristics:
1. Extract Medium polarity solvent systems are often used for extraction to balance the polarity and extraction efficiency of flavonoid glycosides. Common methods include:
* Alcohol extraction method Use methanol, ethanol, or water alcohol mixed solvents with different ratios (such as 70% -80% ethanol) for hot reflux extraction or ultrasound assisted extraction. This method is highly efficient and can simultaneously extract multiple flavonoid glycosides.
* Water extraction method Considering its good water solubility, hot water extraction is also an option, but it may extract more impurities such as polysaccharides and proteins.
2. Enrichment and Separation After vacuum concentration, the crude extract is usually preliminarily enriched using the polarity characteristics of flavonoid glycosides.
* solvent partitioning Ternatumoside II is commonly used for liquid-liquid distribution of ethyl acetate, n-butanol, and water. Due to its strong hydrophilicity, Ternatumoside II is mainly enriched in the n-butanol layer or water layer.
* column chromatography This is a crucial step in separation and purification. Large pore adsorption resins (such as D101, AB-8) are commonly used for column chromatography, with water ethanol gradient elution to preliminarily separate different polar components. Subsequently, further fine separation and purification were carried out by silica gel column chromatography (eluent such as chloroform methanol water system), reverse phase silica gel column chromatography (such as ODS, C18, eluent such as methanol water or acetonitrile water system) or Sephadex gel column chromatography. Among them, reverse phase chromatography is an effective method for obtaining high-purity monomers due to its high polarity matching with flavonoid glycosides.
3. appraisal The isolated pure compounds need to be structurally identified using modern spectroscopic techniques, including ultraviolet spectroscopy (UV), mass spectrometry (MS, such as ESI-MS to determine molecular weight), and one-dimensional and two-dimensional nuclear magnetic resonance spectra (1H NMR, 13C NMR, HSQC, HMBC, COSY, etc.), to accurately determine their planar structure and the connection positions and configurations of sugar groups.

Pharmacological activity research

Although the pharmacological activity research of Ternatumosis II is still in its early stages, it has shown multiple biological effects, mainly focusing on immune regulation and antioxidant aspects.

1. Immune regulatory activity：

   • Stimulate IFN - γ expression This is one of the most prominent activities of Ternatumosis II. Interferon - γ (IFN - γ) is mainly produced by activated T lymphocytes (Th1 cells) and natural killer (NK) cells, and is a core regulatory factor of cellular immune response. It plays a key role in antiviral, anti intracellular bacterial infection, anti-tumor immune surveillance, and immune regulation. Research has shown that Ternatumosis II can significantly stimulate immune cells (such as spleen cells and peripheral blood mononuclear cells) to produce IFN - γ. This activity suggests that it may serve as an immunomodulatory agent or adjuvant for the treatment of diseases associated with insufficient secretion of IFN - γ or low Th1 response, such as certain chronic viral infections, immunodeficiency states, or tumors.

2. antioxidant activity：

   • Free radical scavenging ability Ternatumosis II exhibits clear in vitro free radical scavenging activity. Experimental data showed that its half maximal inhibitory concentrations (IC50) for 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical and 2,2 '- diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) cationic radical were 260.5 μ M and 320.2 μ M, respectively. Although its activity intensity may be weaker than some classic antioxidants such as vitamin C and quercetin glycosides, its clear clearing effect cannot be ignored. The antioxidant capacity of flavonoid glycosides is usually attributed to their phenolic hydroxyl structure, which can neutralize free radicals by providing hydrogen atoms or electrons, interrupting oxidative chain reactions. This antioxidant activity is the basis for its downstream effects such as anti-inflammatory and protection of cells from oxidative damage.

3. Potential associated activity(Based on the activity speculation of its core structure kaempferol and similar flavonoid glycosides):

   • anti-inflammatory activity Many kaempferol glycosides have been shown to inhibit inflammatory signaling pathways such as NF - κ B and MAPK, downregulate the expression of COX-2 and iNOS, and the production of pro-inflammatory cytokines such as TNF - α and IL-6. The immunomodulatory properties of Ternatumosis II suggest that it may also have anti-inflammatory potential.
   • Cardiovascular protection Antioxidant activity is usually associated with cardiovascular protective effects such as protection of vascular endothelial cells, inhibition of LDL oxidation, and anti atherosclerosis.
   • neuroprotection Although its BBB permeability is low, it may have an impact on neuroinflammation by regulating peripheral immunity or indirect effects. Its antioxidant properties may also play a role in preventing peripheral neuropathy.

Mechanism of action and molecular targets

At present, there is insufficient research on the precise molecular mechanism of action of Ternatumosis II, but based on its known IFN - γ stimulatory activity and the commonality of flavonoid glycosides, its potential pathways and targets can be explored.

1. Possible mechanism of stimulating IFN - γ production：

   • Regulating T cell differentiation and activation IFN - γ is mainly produced by Th1 cells and NK cells. Ternatumosis II may promote the secretion of cytokines such as IL-12 by antigen-presenting cells (such as dendritic cells) by affecting their function, thereby driving the differentiation of initial CD4+T cells towards Th1 direction. It may also directly act on T cells or NK cells by activating their internal signaling pathways (such as the JAK-STAT pathway, especially the activation of STAT4, which is crucial for Th1 differentiation and IFN - γ production), upregulating the expression of T-bet (Th1 cell specific transcription factor), thereby promoting the transcription and secretion of IFN - γ genes.
   • Affects signal pathways The common targets of flavonoids include mitogen activated protein kinase (MAPK, such as p38, JNK, ERK), nuclear factor kappa B (NF - κ B), and the JAK-STAT pathway mentioned above. Ternatumosis II may converge to the transcriptional activation of IFN - γ genes by regulating the phosphorylation status or nuclear translocation of these key signaling nodes.
   • Epigenetic regulation Emerging research suggests that some natural products can regulate gene expression by affecting histone modifications or DNA methylation. Whether Ternatumosis II affects the accessibility of IFN - γ gene loci through such mechanisms is worthy of future research.

2. Mechanism of antioxidant action：

   • Directly eliminate free radicals As mentioned earlier, the phenolic hydroxyl group in its molecule is a direct electron/hydrogen donor.
   • Activate endogenous antioxidant system Many flavonoids can exert their effects by activating the nuclear factor E2 related factor 2 (Nrf2) signaling pathway. Nrf2 is a key regulatory factor in cellular antioxidant response, which is activated and transferred to the nucleus. It binds to antioxidant response elements (ARE) and initiates a series of phase II detoxifying enzymes and antioxidant proteins, such as heme oxygenase-1 and HO-1; NAD (P) H: Quinone oxidoreductase 1, NQO1; Superoxide dismutase, SOD; Expression of glutathione peroxidase (GPx). Whether Ternatumosis II exerts indirect and more persistent antioxidant protection through the Keap1-Nrf2-ARE pathway is an important direction for future mechanism research.

3. Potential molecular targets：

   • The specific protein targets have not yet been identified. Possible targets include pattern recognition receptors on the cell surface (such as Toll like receptors, TLRs), intracellular kinases (such as members of the MAPK family mentioned earlier) JAKs）、 Transcription factors (such as STATs, NF - κ B, Nrf2) and related epigenetic regulatory enzymes. Systematic exploration is needed using chemical biology methods such as affinity fishing, molecular docking binding point mutation verification, proteomics, etc.

Evaluation of drug properties and pharmacokinetics

Based on calculations and preliminary experimental data, a preliminary evaluation of the pharmacological properties of Ternatumoside II is conducted

1. Prediction and Challenges of Absorption, Distribution, Metabolism, and Excretion (ADME)：

   • absorb Medium molecular weight (~595) and good water solubility are beneficial for its dissolution in the gastrointestinal tract. However, high polarity (low LogP, high TPSA) may limit its passive diffusion across intestinal epithelial cell membranes, leading to potentially lower oral bioavailability. It may be a substrate for intestinal efflux transporters (such as P-glycoprotein), further affecting absorption. The sugar groups in the structure may be enzymatically hydrolyzed by gut microbiota, releasing the glycoside kaempferol, which has different absorption and metabolic characteristics, forming a possible "prodrug" feature after oral administration.
   • distribution The predicted blood-brain barrier permeability is low, which limits its direct therapeutic application for central nervous system diseases. Its distribution may be more concentrated in tissues such as blood, liver, and kidneys.
   • Metabolism As a flavonoid glycoside, its metabolic pathway may include: ① hydrolysis Under the action of β - glucosidase in the gut microbiota or tissues, glycosides are hydrolyzed to produce kaempferol glycosides. Glycosides undergo further II binding reactions (glucuronidation, sulfation, methylation). ② Direct combination Prototype glycosides may also undergo direct glucuronidation or sulfation. Metabolites are usually more polar and easily excreted.
   • excretion The prototype and its metabolites are mainly excreted through the kidneys (urine) and bile (feces).
   • Experimental requirements Urgent pharmacokinetic studies are needed to determine the blood concentration time curves, absolute bioavailability, tissue distribution, major metabolites, and excretion pathways after oral and intravenous administration.

2. Preliminary evaluation of safety：

   • HERG inhibition negative Reducing the risk of QT interval prolongation and apical torsion ventricular tachycardia is a favorable safety signal.
   • Ames test negative(Result 1.2): Preliminary results indicate no mutagenicity and low risk of genetic toxicity.
   • Subsequent actions are required Acute toxicity testing, repeated dose toxicity testing (14 days, 28 days), and more comprehensive toxicology screening (such as reproductive toxicity, carcinogenicity pre-test) to comprehensively evaluate its safety.

3. Formulation development considerations：

   • Given its potentially low oral bioavailability, formulation strategies may consider: ① Improve solubility and permeability Using cyclodextrin to encapsulate and prepare solid dispersions, nanocrystals, or liposomes. ② Prodrug modification Modify sugar or phenolic hydroxyl groups appropriately to improve lipid solubility. ③ Developing non oral dosage forms Such as injections (utilizing their water solubility), transdermal patches, or inhalants, bypassing the first pass effect.

Clinical application prospects and prospects

Ternatumosis II, as a natural flavonoid glycoside with unique immune regulation and antioxidant activity, its clinical application prospects mainly depend on the results of subsequent in-depth research, and potential directions include:

1. Immune modulators or immune adjuvants：

   • Antiviral infection Ternatumosis II may be used as an adjuvant therapy to enhance the body's specific immune response against viruses that rely on cellular immunity (especially Th1 response and IFN - γ) clearance, such as hepatitis B virus (HBV), human papillomavirus (HPV) persistent infections, and certain herpes virus infections.
   • Tumor immunotherapy adjuvant In the tumor microenvironment, IFN - γ is crucial for activating effector immune cells, inhibiting regulatory T cell (Treg) function, and upregulating MHC-I molecule expression in tumor cells. Ternatumosis II may be used in combination with other immune checkpoint inhibitors, chemotherapy, or radiation therapy to transform "cold tumors" into "hot tumors" and enhance anti-tumor immune effects.
   • vaccine adjuvant Developing new vaccine adjuvants to enhance Th1 type immune response is an important direction. Its natural origin and relative safety make it a potential plant derived immunostimulatory adjuvant.

2. Oxidative stress-related diseases：

   • Metabolic diseases In type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), oxidative stress is the core pathological link. Its antioxidant activity may help improve insulin resistance, alleviate liver steatosis and inflammation.
   • cardiovascular disease As an antioxidant, it may be used for the prevention or auxiliary treatment of atherosclerosis.
   • Inflammatory diseases Many chronic inflammations, such as arthritis and inflammatory bowel disease, are accompanied by oxidative stress. Its potential anti-inflammatory and antioxidant effects may bring benefits.

3. Challenges faced and future research directions：

   • Deep analysis of mechanism It is necessary to clarify the precise molecular targets and signaling pathways that stimulate IFN - γ production, as well as whether its antioxidant effects are mediated through key pathways such as Nrf2.
   • Systematic pharmacodynamic evaluation It is necessary to validate its in vivo activity and determine the effective dose in more relevant animal models of diseases, such as viral infection models, tumor models, and oxidative stress injury models.
   • Comprehensive ADME and toxicology research This is an insurmountable step in advancing its clinical translation.
   • structural optimization Based on structure-activity relationship research, structural modifications are made to the glycosyl portion or aglycone to improve its pharmacokinetic properties while maintaining or enhancing its activity (such as increasing oral bioavailability and regulating distribution characteristics).
   • Multi component collaborative research As a member of natural extracts, studying their synergistic effects with other components in plants, such as other flavonoids and phenolic acids, helps to understand the overall pharmacological substance basis of traditional medicinal materials.

Conclusion

Ternatumoside II, also known as kaempferol-3-O-glucose rhamnoside, is a flavonoid glycoside compound with clear immunostimulatory and antioxidant activity isolated from the traditional medicinal plant R. crenulata. Its unique chemical structure endows it with good water solubility and preliminary safety characteristics. Although current research is still in its early stages, its core activity of stimulating IFN - γ expression provides remarkable lead compounds for the development of novel immunomodulators, antiviral adjuvants, or vaccine adjuvants. Meanwhile, its free radical scavenging ability provides the possibility for intervening in oxidative stress-related diseases. However, in order to translate this potential into practical clinical applications, there is still a lot of basic and translational research work that urgently needs to be carried out, including in-depth elucidation of its molecular mechanism of action, systematic evaluation of its in vivo efficacy and pharmacokinetic characteristics, completion of preclinical safety assessments, and exploration of possible formulation optimization strategies. With the gradual answers to these scientific questions, Ternatumosis II is expected to demonstrate its unique value in the field of natural product drug development, providing new candidate molecules for the treatment of immune imbalances and oxidative stress-related diseases.