Product name: Quercetin 3-gentiobioside
Synonym name:
Catalogue No.: BP1477
Cas No.: 7431-83-6
Formula: C₂₇H₃₀O₁₇
Mol Weight: 626.52
Botanical Source:
Physical Description:
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.

Description:

Quercetin-3-gentiobioside may show significant inhibitor on AR and AGEs formation activities.

References:

Biomed Res Int. 2017;2017:7375615.    

Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds.    

Blocking the polyol pathway plays an important role preventing diabetic complications. Therefore, aldose reductase (AR) and advanced glycation endproducts (AGEs) formation has significant effect on diabetic complications. Artemisia iwayomogi has long been used as treatment of various diseases in Korea. However, no literatures have reported on AR and AGEs formation inhibitory activities of A. iwayomogi. 

METHODS AND RESULTS:

For these reasons, we aimed to assess that A. iwayomogi had potential as anti-diabetic complications agents. We led to isolation of two coumarins (1 and 2), nine flavonoids (3-11), five caffeoylquinic acids (12-16), three diterpene glycosides (17-19), and one phenolic compound (20) from A. iwayomogi. Among them, hispidulin (4), 6-methoxytricin (6), arteanoflavone (7), Quercetin-3-gentiobioside (10), 1,3-di-O-caffeoylquinic acid (13), and suavioside A (18) were first reported on the isolation from A. iwayomogi. Not only two coumarins (1 and 2), nine flavonoids (3-11), and five caffeoylquinic acids (12-16) but also extracts showed significant inhibitor on AR and AGEs formation activities. We analyzed contents of major bioactive compounds in Korea's various regions of A. iwayomogi. 

CONCLUSIONS:

Overall, we selected Yangyang, Gangwon-do, from June, which contained the highest amounts of bioactive compounds, as suitable areas for cultivating A. iwayomogi as preventive or therapeutic agent in the treatment of diabetic complications.    

HPLC of Quercetin 3-gentiobioside

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 attracted much attention in pharmacological research due to their diverse biological activities. Quercetin and its glycoside derivatives are the most representative members, showing great potential in antioxidant, anti-inflammatory, anti-tumor, and metabolic disease intervention. Quercetin 3-gentiobinoside (CAS: 7431-83-6) is a glycoside compound formed by the combination of quercetin and gentian disaccharide (linked by a β -1,6 glycosidic bond between two molecules of glucose) at the C-3 position. Compared with quercetin aglycone, its glycosylation modification significantly changes the physicochemical properties and bioavailability, and endows it with a unique pharmacological activity spectrum. Recent studies have revealed that this compound is not only a powerful aromatase inhibitor (Ki=46.77 nM), but also a dual inhibitor of aldose reductase and advanced glycosylation end products, which has laid a solid scientific foundation for its application in the prevention and treatment of hormone dependent breast cancer, diabetes and its complications. 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 Quercetin-3-gentian glycoside, in order to provide comprehensive theoretical references for the deep development and transformation research of this natural product.

Chemical structure and physicochemical properties

The molecular formula of Quercetin-3-Gentianacide is C27H30O17, with a molecular weight of 626.5200. Its core structure is the flavonoid skeleton composed of the A and C rings of quercetin (3,5,7,3 ', 4' - pentahydroxyflavone), and its characteristic 3-hydroxy site is connected to Gentiobiose through O-glycosidic bonds. Gentian disaccharide is a rare disaccharide with a β - D-glucosyl - (1 → 6) - β - D-glucose linkage. This structure is different from common rutin or glucoside, and may affect its interaction with target proteins and metabolic fate in vivo.

In terms of physicochemical properties, the introduction of highly hydrophilic gentian disaccharide groups significantly altered the polarity of the compound. Its theoretical distribution coefficient (LogP) is -1.0535, indicating its high hydrophilicity. The topological polar surface area (TPSA) is as high as 289.6600 Å ², further confirming its strong polarity characteristics. The predicted value of water solubility is 4.3091, which belongs to the soluble range, which is beneficial for its development in water-based formulations. However, high polarity and high molecular weight also pose challenges to its biofilm permeability, and it is predicted that its blood-brain barrier permeability is low, mainly affecting the peripheral system. The preliminary drug risk assessment shows that the hERG channel inhibition risk is negative, and the Ames test value is 1.2 (usually considered>1.5 as potential mutagenicity positive, which needs to be judged based on specific experiments), indicating that its cardiac toxicity and genetic toxicity risks are low, and it has a relatively good safety starting point.

Plant sources and extraction methods

Quercetin-3-gentian glucoside has a relatively specific distribution in the plant kingdom, mainly found in certain medicinal and edible plants. According to literature reports, it is Ginkgo leaf、Gynostemma pentaphyllum、Sea buckthorn leaves And some Rhododendron family The content is relatively abundant in plants. In addition, it is also detected in some traditional herbs used to treat diabetes or inflammation, suggesting that its biological activity may be related to the traditional efficacy of plants.

Its extraction and separation usually follow the conventional process of natural product chemistry. Firstly, methanol, ethanol, or ethanol water mixed solvents are used for extraction or ultrasound assisted extraction of dried plant materials to fully obtain flavonoid components. After filtration and concentration, the crude extract was preliminarily enriched and purified using macroporous adsorption resins (such as AB-8, D101). Through gradient elution with different concentrations of ethanol aqueous solutions, quercetin glycosides were mainly concentrated in the elution sites with medium to high concentrations of ethanol. Further separation and purification rely on chromatographic techniques, including silica gel column chromatography, polyamide column chromatography, and high-performance liquid chromatography (HPLC) preparative chromatography. A reverse phase C18 chromatographic column combined with water methanol or water acetonitrile (often containing small amounts of formic acid or acetic acid to improve peak shape) gradient elution is an effective method for separating this compound. Its identification mainly relies on mass spectrometry (MS, providing molecular weight and fragment ion information) and nuclear magnetic resonance spectroscopy (NMR, especially 1H-NMR and 13C-NMR, which can accurately analyze the position and configuration of sugar linkage). In recent years, efficient preparation techniques such as high-speed countercurrent chromatography have also been applied to the rapid separation of such compounds.

Pharmacological activity research

Quercetin -3- Gentianobioside shows many pharmacological activities, mainly focusing on anti-tumor, anti diabetes complications and antioxidant.

1. Antitumor activity (especially for breast cancer)One of its most prominent activities is as a potent aromatase inhibitor. Aromatase is a key rate limiting enzyme in estrogen biosynthesis, which can convert androgen into estrogen and plays a central role in the occurrence and development of hormone dependent breast cancer. Quercetin-3-gentianobioside can competitively inhibit aromatase activity with an affinity of nanomolar level (Ki=46.77 nM), thereby reducing the production of estrogen in the local tumor, theoretically inhibiting the proliferation of estrogen dependent breast cancer cells. This activity makes it a potential candidate molecule for chemoprevention or adjuvant therapy of breast cancer.

2. Anti diabetes and its complications：

   • Aldose reductase inhibition Under hyperglycemic conditions, the polyol pathway is overactivated, with aldose reductase (AR) converting glucose to sorbitol being the key first step. Sorbitol accumulation leads to oxidative stress and cell damage, which is an important mechanism of diabetes neuropathy, cataract and other complications. This compound exhibits significant inhibitory activity against AR (IC50=10.60 μ M) and can effectively block this pathological pathway.
   • Inhibition of advanced glycation end product formation Long term hyperglycemia leads to non enzymatic glycosylation of proteins, lipids, etc., forming irreversible late glycation end products (AGEs). The accumulation of AGEs through their receptors (RAGE) triggers inflammation and oxidative stress, leading to vascular and organ damage. This compound can inhibit the formation of AGEs (IC50=109.46 μ M), which is helpful to delay the progress of chronic complications such as diabetes nephropathy, retinopathy and atherosclerosis.

3. Antioxidant and anti-inflammatory activities As a derivative of quercetin, it has direct free radical scavenging ability. More importantly, studies have shown that it can upregulate the gene expression of downstream antioxidant enzymes and phase II detoxifying enzymes, such as superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPX1), and heme oxygenase-1 (HMOX1), by regulating the nuclear factor E2 related factor 2 (NRF2/NFE2L2) signaling pathway, thereby enhancing the endogenous antioxidant defense system of cells. At the same time, it can also inhibit the expression of matrix metalloproteinases (such as MMP1, MMP3), which play an important role in inflammation and tissue remodeling. The potential inhibitory effect on tyrosinase (TYR) also suggests its potential application in skin pigmentation related diseases.

Mechanism of action and molecular targets

The multiple pharmacological activities of Quercetin-3-Gentianacide stem from its regulation of multiple key molecular targets, forming a multi-target network.

1. Direct enzyme inhibition：

   • Aromatase (CYP19A1)By binding to the active site of the enzyme through its flavonoid structure, it competitively inhibits the binding of the substrate androstenedione to the heme iron atom, thereby blocking estrogen synthesis.
   • Aldehyde reductase (AKR1B1)The phenolic hydroxyl group in its molecule may form hydrogen bonds or interact with the active center amino acid residues of the enzyme, inhibiting the conversion of glucose to sorbitol.
   • AGEs formation related proteins May interfere with glycosylation reactions by binding to amino or carbonyl intermediates of proteins.

2. Signal pathway regulation：

   • NRF2/KEAP1 pathway This compound may dissociate NRF2 from the KEAP1 complex and translocate it to the nucleus by modifying cysteine residues on the KEAP1 protein. It binds to antioxidant response elements and initiates transcription of genes such as SOD, CAT, GPX1, HMOX1, systematically enhancing the cell's antioxidant stress resistance.
   • NF - κ B pathway Its anti-inflammatory effect may be partially achieved by inhibiting the activation of NF - κ B, thereby reducing the expression of downstream inflammatory factors and MMPs. The inhibition of MMP1 and MMP3 is directly related to the pathological process of anti photoaging and anti atherosclerotic plaque instability.

3. Indirect antioxidant In addition to directly clearing free radicals and activating the NRF2 pathway, upregulated antioxidant enzymes (such as SOD, CAT, GPX1) can work synergistically to convert reactive oxygen species such as superoxide anions and hydrogen peroxide into harmless water and oxygen, forming a strong cell protective barrier. The upregulation of HMOX1 not only has antioxidant effects, but also produces carbon monoxide and biliverdin, exerting anti-inflammatory and cell protective effects.

Evaluation of drug properties and pharmacokinetics

Although Quercetin-3-gentiopicroside exhibits excellent biological activity in vitro, its pharmacological properties, especially its pharmacokinetic properties in vivo, are the key to determining its successful development.

• Absorption and distribution As a highly polar glycoside compound, its oral absorption may be limited. It is speculated that its absorption site is mainly in the small intestine, possibly through sodium dependent glucose transporter 1 (SGLT1) or passive diffusion (after deglycosylation). The blood-brain barrier permeability of the prototype drug or metabolite is low, which is consistent with its predicted physicochemical properties. This means that its direct effect on central nervous system related diseases is limited, but it also reduces the potential risk of central side effects.
• Metabolism After glycoside compounds enter the body, they are easily hydrolyzed by β - glucosidase in the gut microbiota or intestinal mucosal epithelial cells, releasing quercetin glycosides and gentian disaccharides or glucose. Quercetin glycosides can then be absorbed and undergo extensive phase II metabolism, such as glucuronidation, sulfation, and methylation, to form various metabolites. Therefore, its in vivo activity is likely the result of the combined action of the prototype drug, aglycones, and their metabolites (the "prodrug" effect). The structure of gentian disaccharides may affect their hydrolysis rate and site, thereby altering their bioavailability.
• excretion Metabolites are mainly excreted through urine and bile.
• Challenges and optimization of drug development The main challenge is that the oral bioavailability may be low. Future formulation strategies may consider: 1) Development Predrug or structural modification For example, preparing liposomes, nanoparticles, phospholipid complexes, or performing appropriate esterification modifications to improve their lipid solubility and membrane permeability; 2) Utilize New drug delivery system, such as self microemulsions, solid dispersions, or cyclodextrin inclusion complexes, to improve their solubility and stability; 3) Explore Non oral administration route For topical application (for skin diseases) or injection administration (to address issues of water solubility and stability). The good preliminary safety data of hERG and Ames provide support for its further development, but comprehensive preclinical toxicology studies still need to be conducted.

Clinical application prospects and prospects

Based on its unique pharmacological mechanism of action, Quercetin-3-gentiopicroside has broad development prospects in multiple disease fields:

1. Adjuvant treatment and prevention of breast cancer As a highly effective and natural aromatase inhibitor, it is expected to be developed as an adjuvant drug for endocrine therapy of breast cancer or used for chemoprevention of high-risk groups. Combined with existing synthetic aromatase inhibitors such as itraconazole and anastrozole, it may produce synergistic effects or reduce their side effects.
2. Prevention and treatment of complications of diabetes Its dual inhibition of the formation of AR and AGEs makes it a potential multi target drug for the prevention and treatment of diabetes neuropathy, nephropathy, retinopathy and cardiovascular complications. It can be considered to develop as plant medicine or functional food additive for chronic complications of diabetes.
3. Antioxidant and anti-aging related products The strong NRF2 activation ability makes it promising in the fields of cosmetics or topical drugs for antioxidant, anti-aging, and anti skin inflammation (such as dermatitis). Inhibition of MMPs is also applicable for preventing skin collagen degradation caused by ultraviolet radiation.
4. Combination therapy and multi-component drug development Given its multi-target nature, it may be considered to be used in combination with drugs with other mechanisms of action (such as metformin, antioxidants), or to develop compound formulations with other natural products with synergistic effects (such as resveratrol, curcumin) for the treatment of complex diseases such as metabolic syndrome and chronic inflammation.

Future research should focus on: 1) further elucidating its in vivo metabolic profile and main active forms; 2) Use animal models (such as breast cancer transgenic mice, diabetes complication models) to verify its efficacy and safety in vivo; 3) Carry out systematic pharmaceutical research to overcome its bioavailability bottleneck; 4) Explore its interactions with other targets such as inflammasomes and autophagy pathways to expand its new indications.

Conclusion

As a natural flavonoid glycoside, quercetin-3-gentianobioside, with its unique gentianobiose group, not only optimizes the physical and chemical properties of quercetin mother nucleus, but also endows it with powerful aromatase inhibition and dual inhibition ability against key pathways of diabetes complications (AR and AGEs). Its multi-target mechanism of action, especially the activation of the NRF2 antioxidant defense system, constitutes the molecular basis of its antioxidant, anti-inflammatory, anti-tumor, and metabolic regulatory activities. Although there are challenges in developing drug properties such as oral absorption, these obstacles can be overcome through the optimization of modern medicinal chemistry and formulation methods. With the in-depth study of its pharmacological mechanism and in vivo process, quercetin-3-gentianoside is expected to develop from a potential lead compound into an innovative drug or functional product with important value in the fields of adjuvant treatment of breast cancer, prevention and control of diabetes complications and oxidative stress related diseases, fully demonstrating the eternal charm of natural products as a treasure house of drug discovery.