Product name: Quercetin 3-O-β-D-xylopyranoside
Synonym name:
Catalogue No.: BP3340
Cas No.: 549-32-6
Formula: C₂₀H₁₈O₁₁
Mol Weight: 434.353
Botanical Source:
Physical Description: Yellow powder
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
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 Quercetin 3-O-β-D-xylopyranoside

HNMR of Quercetin 3-O-β-D-xylopyranoside

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

Introduction/Overview

Flavonoids, as one of the most widely distributed plant secondary metabolites in nature, have long been of great concern due to their extensive biological activities. Quercetin, as a typical representative of flavonol compounds, has been extensively studied for its anti-inflammatory, antioxidant, and anti-tumor pharmacological effects. However, quercetin itself has drug defects such as poor water solubility and low oral bioavailability, which limits its clinical application. Nature has ingeniously generated various quercetin glycoside derivatives through glycosylation modification, which often exhibit unique advantages in improving solubility, enhancing stability, and regulating biological activity. Quercetin 3-O - β - D-xylopyroside (Q3X) is one of the important monoglycosides.

Q3X, CAS number 549-32-6, is an O-glycoside formed by the glycosidic bond between the hydroxyl group at position 3 of the C-ring of quercetin and the β - D-xylopyranose group. Compared with common glucosides or rhamnoides, the xylose groups connected to it have special structures and properties, which may bring differentiated biological effects. This compound was originally derived from the leguminous plant Mimosa pudica（Mimosa pudica L. It was isolated and subsequently discovered in various other medicinal plants. In recent years, with the advancement of natural product separation and identification technology and the deepening of molecular pharmacology research, Q3X has surpassed the unique pharmacological activity of its parent nucleus quercetin, especially in its potential for antioxidant and related disease intervention, gradually becoming a research hotspot. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, medicinal properties, and clinical application prospects of Q3X, 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 Quercetin-3-O - β - D-xyloside is C20H18O11, with a molecular weight of 434.35 g/mol. Its core structure is the classic 2-phenylchromatone-4-one skeleton, also known as the quercetin mother nucleus. Quercetin itself is a pentahydroxyflavonoid, with two phenolic hydroxyl groups at positions 5,7-on its A ring, two adjacent phenolic hydroxyl groups at positions 3 ', 4' - on its B ring, and one alcohol hydroxyl group at position 3 on its C ring. The structural feature of Q3X is that the hydroxyl group at position 3 of its C-ring forms a glycosidic bond with a molecule of β - D-xylopyranose.

Xylose is a five carbon aldose (pentose), and its pyran ring form is connected to quercetin in a β configuration in Q3X. Compared with common six carbon sugar glucosides, the xylose group lacks a - CH2OH group, resulting in smaller molecules and slightly different hydrophilicity. This structural modification has a decisive impact on the physicochemical properties of the compound. The calculated lipid water partition coefficient (LogP) is 0.4784, indicating that the compound has moderate lipophilicity, but compared to quercetin (LogP of approximately 1.5-2.0), its hydrophilicity is significantly enhanced. The topologically polar surface area (TPSA) is as high as 190.28 Å ², mainly attributed to the numerous hydrogen bond acceptors (oxygen atoms) in the molecule. The theoretical water solubility value is 0.7123, which confirms that its solubility in water is better than that of quercetin. These physicochemical parameters suggest that Q3X may have better fluid solubility and formulation processing performance.

The presence of glycosidic bonds also affects the chemical stability of compounds. 3-glycosylation protects the hydroxyl group at that position, which may alter the sensitivity of the molecule to oxidative degradation. At the same time, as a glycoside, it is easily hydrolyzed by glycosidases in the intestine and blood in the body, which may generate secondary glycosides, which is one of the key characteristics of its pharmacokinetic behavior.

Plant sources and extraction methods

Q3X is not universally present in the plant kingdom, but has been identified in multiple families of plants, demonstrating a certain degree of distribution specificity.
1. Main plant sources：
* Fabaceae (Fabaceae)It is the earliest and most famous source. Mimosa plant（Mimosa pudica L. The whole grass or leaves of Q3X are classic raw materials for isolation. In addition, in some Astragalus species（Astragalus）It has also been detected in plants.
* Other families and genera Research reports that it is found in the Primulaceae family (such as Forsythia suspensa)Hypericum perforatum）It exists in some plants such as Asteraceae and Rosaceae, and often coexists with other flavonoid glycosides.

1. Extraction and Separation Methods：
   The extraction and separation of Q3X follows the general process of plant polyphenolic components, but optimization is needed for its polarity and stability.
   • Extract Methanol, ethanol, or their aqueous solutions (such as 70-80% ethanol) are commonly used for reflux extraction or ultrasound assisted extraction. Ethanol aqueous solution is commonly used for large-scale preliminary extraction due to its low cost and low toxicity. Modern technologies such as microwave-assisted extraction and pressurized solvent extraction can help improve extraction efficiency and save time.
   • Separation and purification The crude extract is initially defatted and segmented using solvents such as petroleum ether and ethyl acetate, and the portion rich in polar flavonoid glycosides (usually present in n-butanol or aqueous layers) is the target. Further purification is highly dependent on chromatographic techniques.
     • Column chromatography Silica gel column chromatography, polyamide column chromatography, or reverse phase silica gel (such as ODS-C18) column chromatography are commonly used for preliminary separation. Macroporous adsorption resins (such as D101, AB-8) are also commonly used for enrichment and decolorization.
     • High performance liquid chromatography Prepa HPLC is the most critical step in obtaining high-purity Q3X monomers. Usually, a reverse phase C18 chromatography column is used, with methanol water or acetonitrile water (often containing a small amount of formic acid or acetic acid to adjust pH) as the mobile phase for gradient elution. Monitor the characteristic absorption wavelength of flavonoids (such as around 254 nm or 360 nm) using a UV detector.
   • appraisal The structural identification of compounds mainly relies on spectroscopic methods. UV spectroscopy can indicate the flavonoid mother nucleus and hydroxyl substitution mode. Mass spectrometry (MS, especially ESI-MS or HR-MS) can provide precise molecular weight and fragment ion information of glycosidic bond cleavage. Nuclear magnetic resonance spectroscopy (NMR, including 1H NMR, 13C NMR, HSQC, HMBC, etc.) is the gold standard for analyzing its planar and three-dimensional structure, which can clarify the chemical shifts of protons and carbons on the quercetin mother nucleus, as well as the connection position (3rd position) and glycosidic bond configuration (β - type) of the xylose group.

Pharmacological activity research

A large number of in vitro and in vivo studies have shown that Q3X inherits some of the biological activities of quercetin and exhibits new characteristics due to its unique glycosylation modification. Its core pharmacological activity revolves around strong antioxidant effects and extends to multiple related fields.

1. Core antioxidant activity The antioxidant capacity of Q3X is its most prominent characteristic. The phenolic hydroxyl group in its molecule (especially the ortho dihydroxy group in the B ring) is an active group that provides electrons and can effectively scavenge free radicals such as DPPH radicals, ABTS ⁺ radicals, superoxide anions (O ₂⁻ •), and hydroxyl radicals (• OH). Research has shown that its ability to scavenge free radicals is comparable to or even stronger than quercetin in certain systems, which may be related to the introduction of sugar groups that alter the electron distribution of molecules and their reactivity with free radicals. In cell models, Q3X can significantly reduce the levels of reactive oxygen species (ROS) induced by hydrogen peroxide (H ₂ O ₂), lipopolysaccharide (LPS), or other stimuli, protecting cells from oxidative stress damage.

2. anti-inflammatory effect Oxidative stress is closely linked to inflammatory response. Q3X indirectly exerts anti-inflammatory effects through its antioxidant properties. Research has shown that it can inhibit the excessive production of nitric oxide (NO) and prostaglandin E2 (PGE2) in macrophages (such as RAW264.7) stimulated by lipopolysaccharide (LPS), and downregulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, it also has inhibitory effects on the secretion of various pro-inflammatory cytokines such as TNF - α, IL-1 β, IL-6.

3. Skin protection and anti photoaging Based on its antioxidant and anti-inflammatory properties, Q3X has attracted much attention in dermatopharmacology. Research has shown that it can inhibit the activity of tyrosinase (TYR), suggesting its potential whitening effect. More importantly, in the UV induced skin photoaging model, Q3X can inhibit the overexpression of matrix metalloproteinases (such as MMP-1, MMP-3) by clearing ROS. MMPs are key enzymes that degrade collagen and elastin in the dermis of the skin, and their activity is activated by UV through the ROS pathway. Therefore, Q3X has the potential to be applied in functional cosmetics and topical medications for the skin by protecting the extracellular matrix and delaying photoaging through antioxidant inhibition of the MMPs pathway.

4. Neuroprotective potential Although its blood-brain barrier permeability is low, some studies suggest that it may have a protective effect on neurodegenerative disease-related models. In neuronal injury models induced by oxidative stress or β - amyloid protein, Q3X can increase cell survival rate and reduce apoptosis. The mechanism may be related to the activation of the intracellular antioxidant defense system.

5. Other potential activities: Preliminary research also suggests that Q3X may have anti diabetes (by protecting pancreatic beta cells from oxidative damage), cardiovascular protection (by reducing endothelial cell oxidative damage) and other activities, but research in these fields is still in its infancy and needs more evidence to support.

Mechanism of action and molecular targets

The pharmacological effects of Q3X are not simply the direct quenching of free radicals, but involve a complex regulatory network with multiple targets and pathways. Its core mechanism revolves around regulating cellular redox balance.

1. Direct antioxidant and enzyme inhibition：

   • free radical scavenging As a hydrogen donor, it directly neutralizes various free radicals.
   • Metal ion chelation The adjacent phenolic hydroxyl group can chelate transition metal ions such as Fe ² ⁺ and Cu ² ⁺, inhibit the Fenton reaction, and prevent the generation of • OH.
   • Direct enzyme inhibition It can directly bind to the active center of tyrosinase (TYR), competitively inhibit its catalytic activity, and reduce melanin synthesis. Similarly, the activity of MMPs may be influenced through direct interactions.

2. Activate endogenous antioxidant defense system - NRF2/ARE pathway This is the core molecular mechanism by which Q3X exerts cell protective effects. Nuclear factor E2 related factor 2 (NRF2, encoded by NFE2L2 gene) is a key transcription factor that regulates cellular antioxidant stress response. At rest, NRF2 binds to the cytoplasmic chaperone protein Keap1 and is degraded by ubiquitination. When subjected to oxidative stress or certain compounds (such as Q3X), NRF2 dissociates from Keap1, translocates to the nucleus, binds to antioxidant response elements (ARE), and initiates the transcriptional expression of downstream phase II detoxifying enzymes and antioxidant proteins.

   • Key target genes Q3X significantly upregulates the expression of key antioxidant enzymes such as heme oxygenase-1 (HMOX1), superoxide dismutase (SOD1, SOD2), catalase (CAT), and glutathione peroxidase (GPX1) by activating NRF2. The induction of HMOX1 is considered a hallmark event of NRF2 activation, and its products bilirubin and CO have strong antioxidant and anti-inflammatory effects. SOD, CAT, and GPX constitute a cascade enzyme system for cell clearance of ROS. This systematic upregulation fundamentally enhances the cell's ability to resist oxidative damage.

3. Inhibition of inflammatory signaling pathway The anti-inflammatory effect of Q3X is closely related to its inhibition of classic pro-inflammatory signaling pathways such as NF - κ B and MAPK. It can inhibit the degradation of I κ B α and nuclear translocation of NF - κ B p65 subunit, thereby blocking the transcriptional activity of NF - κ B and reducing the expression of iNOS, COX-2, and various inflammatory cytokines. Meanwhile, it can also inhibit the phosphorylation activation of kinases such as JNK and p38 MAPK.

4. Inhibition of extracellular matrix degradation In the skin photoaging model, Q3X inhibits UV induced activation of AP-1 transcription factor through the aforementioned antioxidant and anti-inflammatory mechanisms, thereby downregulating the transcription and expression of its target genes MMP-1 and MMP-3, thereby protecting collagen and maintaining skin structural integrity.

In summary, the mechanism of action of Q3X is a three-dimensional network that involves direct antioxidant activity, activation of endogenous defense, and regulation of downstream inflammation and matrix metabolic pathways. NRF2 is a key hub molecule that plays a core protective role.

Evaluation of drug properties and pharmacokinetics

Although Q3X exhibits excellent activity in vitro, it still needs to cross the threshold of drug development to become a drug. Based on computational parameters and limited experimental data, a preliminary evaluation of its pharmacological properties can be conducted.

1. Preliminary analysis of the five principles of generic drugs：

   • molecular weight 434.35, slightly higher than the ideal value (<500), but still within an acceptable range.
   • LogP 0.48 indicates good hydrophilic and lipophilic balance, which is conducive to absorption.
   • Hydrogen bond donor/acceptor The molecule contains multiple hydrogen bond donors (phenolic hydroxyl groups) and acceptors (carbonyl, ether bonds), with a high TPSA value (190.28), which is usually unfavorable for passive transmembrane diffusion, especially through the blood-brain barrier.
   • Number of rotatable keys Moderate, does not affect molecular rigidity.

2. Key pharmacological parameters：

   • Water solubility Theoretical values and experiments have shown that its water solubility is significantly better than quercetin, which is beneficial for making oral, injection or topical preparations.
   • Blood-brain barrier permeability Predicted as' low '. This is consistent with its higher TPSA and polarity, indicating that it is difficult to enter the central nervous system, which is disadvantageous for the treatment of central target diseases, but may also reduce the risk of central nervous system side effects.
   • Cardiac safety (hERG inhibition)A prediction of 'no' indicates a lower potential risk of cardiac toxicity, which is an important safety advantage.
   • Genotoxicity (Ames test)The predicted value is 1.2, and it is generally considered negative if it is less than 1.5, indicating a low risk of mutagenicity.

3. Pharmacokinetic prediction and challenges：

   • absorb As a highly polar glycoside, its absorption in the small intestine may involve active transport (such as glucose transporter SGLT1) or passive diffusion, but the efficiency is usually lower than that of aglycones. Glycosidases in the gut microbiota may hydrolyze it into quercetin and xylose, which are then absorbed. This is a common metabolic pathway for flavonoid glycosides.
   • distribution Due to its high polarity, it is predicted that its plasma protein binding rate may be moderate, and its tissue distribution may be biased towards organs with abundant blood flow such as the kidneys and liver, making it difficult to widely distribute to adipose tissue and the central nervous system.
   • Metabolism In addition to possible intestinal hydrolysis, it may undergo phase II binding reactions (glucuronidation, sulfation) in the liver. The presence of xylose groups may affect their metabolic patterns and rates.
   • excretion It is speculated that it is mainly excreted through the kidneys and bile.
   • bioavailability Taking into account factors such as absorption and metabolic first pass effects, the oral absolute bioavailability of most flavones may not be high, which is a common challenge faced by most flavones. Formulation technologies such as nanocrystals, phospholipid complexes, and cyclodextrin inclusion complexes may be key to improving their bioavailability.

At present, there is a severe lack of research data on the pharmacokinetics of the Q3X system, which is a gap that must be filled in future translational studies.

Clinical application prospects and prospects

Based on its unique pharmacological activity and relatively good safety prediction, Q3X has potential application value in multiple fields.

1. Dermatology and cosmetics field This is currently the most promising direction for direct application.

   • Functional cosmetic additives As a highly effective natural antioxidant and tyrosinase inhibitor, it can be used to develop high-end skin care products such as essence, lotion and facial mask that can resist aging, whitening and light damage.
   • external medication Can be used to treat or assist in the treatment of skin diseases related to oxidative stress and inflammation, such as photodermatitis, skin photoaging, post inflammatory pigmentation, etc. It can be developed into cream, gel and other dosage forms.

2. Adjuvant treatment for chronic inflammatory diseases: In view of its anti-inflammatory and antioxidant effects, Q3X or plant extracts containing Q3X may be used as dietary supplements or auxiliary drugs to manage chronic low-grade inflammatory diseases such as arthritis, atherosclerosis, metabolic syndrome, etc. Further animal models and clinical studies are needed for validation.

3. Prevention of neurodegenerative diseases Although BBB has poor permeability, its metabolite quercetin may be able to pass through BBB. In addition, after modification through pharmaceutical methods such as targeted delivery with nanocarriers, it may be used for preventive intervention research in diseases such as Alzheimer's disease and Parkinson's disease.

4. Challenges faced and future research directions：

   • Systematic pharmacodynamic and pharmacokinetic studies It is urgent to validate its in vivo activity in animal models (especially disease models) and conduct complete ADME studies to clarify its in vivo fate.
   • Deep exploration of the mechanism of action Using omics techniques (transcriptomics, proteomics, metabolomics) to comprehensively reveal its functional network and discover new targets of action.
   • Structural optimization and derivative development Using it as a lead compound, improve its pharmacokinetic properties through chemical modifications (such as preparing prodrugs, synthesizing more lipophilic derivatives), especially enhancing oral bioavailability and tissue targeting.
   • Formulation technology development Explore nano delivery systems (liposomes, polymer nanoparticles), microemulsions, transdermal penetration enhancement techniques, etc., to overcome their limitations in solubility, stability, and absorption.
   • Preclinical safety evaluation Conduct systematic GLP compliance studies on acute toxicity, chronic toxicity, reproductive toxicity, etc., laying the foundation for clinical research application.
   • Resources and Sustainable Production Plant extraction is influenced by season and place of origin, and chemical or biological synthesis (such as microbial fermentation and synthetic biology) is the future direction to ensure stable and sustainable supply.

Conclusion

Quercetin-3-O - β - D-xyloside, as a naturally occurring quercetin xyloside, exhibits enhanced hydrophilicity and unique biological effects due to its unique chemical structure, while inheriting the broad-spectrum biological activity of quercetin. Its strong antioxidant capacity, especially by activating the NRF2/ARE pathway to enhance the core mechanism of cellular defense system, provides a solid scientific basis for its application in oxidative stress-related diseases, especially skin photoaging and chronic inflammation. Despite facing common challenges such as oral bioavailability and blood-brain barrier permeability in drug development, its good water solubility, predicted low cardiac toxicity, and genetic toxicity have laid a safe foundation for its development. In the future, through in-depth pharmacological mechanism research, systematic pharmacokinetic evaluation, and advanced formulation technology and structural modification strategies, Quercetin-3-O - β - D-xyloside is expected to gradually move from a potential natural product molecule to clinical applications, providing important candidate substances for the development of new antioxidant, anti-inflammatory, skin protective drugs or functional products.