Synonym name: Genistein 4'-glucoside
Catalogue No.: BP1326
Cas No.: 152-95-4
Formula: C₂₁H₂₀O₁₀
Mol Weight: 432.381
Botanical Source: Sophora japonica and Piptanthus nepalensis

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

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

HPLC of Sophoricoside

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

Introduction/Overview

Natural products have always been an important source of innovative drug discovery, among which isoflavone compounds have attracted much attention due to their wide range of biological activities. Sophoricoside, also known as 5,4 '- dihydroxyflavone-7-O - β - D-glucopyranoside, is an isoflavone glycoside isolated from the traditional medicinal plant Sophora japonica L. Since its discovery, research has revealed its significant potential in anti-inflammatory, anticancer, and immune regulation, making it a hot topic in pharmacological research. In recent years, with the increasingly clear role of oxidative stress in the occurrence and development of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and cancer, natural compounds with antioxidant activity have shown great potential for application. Huaijiao glycoside regulates the antioxidant defense system centered on nuclear factor E2 related factor 2 (NRF2, encoded by NFE2L2 gene), exerting its antioxidant damage effect, laying a theoretical foundation for its prevention and treatment of oxidative stress-related diseases. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, especially the mechanism and molecular targets of antioxidant damage of sophora flavescens, and to prospect its pharmacological properties and clinical application prospects.

Chemical structure and physicochemical properties

The molecular formula of sophora japonica glycoside is C21H20O10, with a molecular weight of 432.3810. Its chemical structure is based on isoflavones as the mother nucleus, specifically composed of the 7th hydroxyl group of 5,7,4 '- trihydroxyflavone (genistein) connected to a molecule of β - D-glucose through glycosidic bonds. This glycosidic structure significantly affects its physicochemical properties.

From the perspective of pharmacological parameters, the theoretical lipid water partition coefficient (LogP) of sophocarpine is 0.1579, indicating its good hydrophilicity. Its topological polar surface area (TPSA) is as high as 170.0500 Å ², mainly attributed to the numerous hydrogen bond acceptors (oxygen atoms) in the molecule. The higher TPSA and lower LogP together determine its good water solubility, with a calculated value of approximately 1.1047 mg/mL. These properties suggest that the absorption and distribution of sophora flavescens glycosides in the body may face challenges, especially as their blood-brain barrier permeability is predicted to be "low", which limits their direct effects on central nervous system diseases. However, its good water solubility is beneficial for formulation development. In terms of preliminary safety evaluation, sophora flavescens has no significant inhibitory effect on hERG potassium channels (hERG inhibition: No), indicating a low risk of causing QT interval prolongation in the heart. The Ames test result was 1.2, indicating that no significant mutagenicity was observed under the experimental conditions, providing preliminary safety evidence for its further development.

Plant sources and extraction methods

Sophora japonica L., a legume plant, is the main source of Sophora japonica glycosides. Its flower buds (Sophora japonica) and fruits (Sophora japonica) are the main medicinal parts. As a traditional Chinese medicine, Sophora japonica has a bitter and slightly cold taste, and belongs to the liver and colon meridians. It has the effects of cooling blood, stopping bleeding, clearing liver and purging fire, and is commonly used to treat symptoms such as rectal bleeding, hemorrhoids, dysentery, diarrhea, liver heat, and blurred vision. Huaijiao glycoside is one of the key active ingredients that exert pharmacological effects in Huaihua and Huaijiao.

The extraction of sophocarpin from plant materials is usually carried out using solvent extraction method. Common solvents include methanol, ethanol, or their aqueous solutions. In order to improve extraction efficiency, modern extraction techniques such as ultrasound assisted extraction, microwave-assisted extraction, and supercritical fluid extraction have been widely used. For example, using a 70% ethanol solution for ultrasonic extraction can effectively shorten the extraction time and improve the yield of sophocarpin. After filtration and concentration, the extraction solution is usually preliminarily enriched and purified using macroporous adsorption resin column chromatography. Commonly used resins such as AB-8 and D101 have good adsorption and desorption properties for sophocarpin. Further purification can be achieved through techniques such as silica gel column chromatography and preparative high-performance liquid chromatography to obtain high-purity sophoricoside monomers for in-depth pharmacological and mechanistic studies.

Pharmacological activity research

Sophora japonica glycoside exhibits diverse pharmacological activities, mainly including the following aspects:

1. Antioxidant damage activity This is one of the core pharmacological activities of sophora flavescens glycoside. Numerous in vitro studies have shown that sophora flavescens can effectively scavenge free radicals such as DPPH and ABTS, and alleviate cellular oxidative damage caused by hydrogen peroxide (H ₂ O ₂), lipopolysaccharide (LPS), or other oxidative stress inducers. In various cell models such as endothelial cells, neuronal cells, and liver cells, pre-treatment with sophocarpine can significantly improve cell survival rate, reduce intracellular reactive oxygen species (ROS) levels, decrease the production of lipid peroxidation product malondialdehyde (MDA), and enhance the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX).

2. anti-inflammatory effect Inflammation is closely related to oxidative stress. Huaijiao glycoside exerts anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators such as tumor necrosis factor - α, interleukin-6, and nitric oxide, as well as downregulating the expression of inducible nitric oxide synthase and cyclooxygenase-2. It has also demonstrated good anti-inflammatory effects in animal models such as mouse ear swelling, arthritis, and colitis models.

3. anticancer activity Sophoroside can inhibit the growth and induce apoptosis of many cancer cell lines (such as breast cancer, liver cancer, colon cancer and lung cancer). Its anti-cancer mechanism involves cell cycle arrest, induction of apoptosis, inhibition of invasion and metastasis, etc. It is worth noting that its antioxidant activity may play a dual role in anti-cancer: on the one hand, it protects normal cells by clearing ROS; On the other hand, in some cancer cells, cancer cell death may be promoted by regulating the redox balance.

4. Immune regulatory effect Huaijiao glycoside has been reported to have immunosuppressive activity, which can inhibit the excessive proliferation of T lymphocytes and B lymphocytes, regulate cytokine secretion, making it potentially valuable in the treatment of autoimmune diseases such as rheumatoid arthritis.

5. Other activities The study also suggests that sophocarpine has certain effects in protecting bone density (anti osteoporosis) and improving insulin resistance.

Mechanism of action and molecular targets

The various pharmacological activities of sophora flavescens, especially its core antioxidant damage effect, are closely related to its regulation of specific molecular signaling pathways and targets. The core of its mechanism of action network is the NRF2/ARE pathway.

• Core pathway: NRF2/ARE signaling pathway
  NRF2 is a central regulatory factor of cellular antioxidant response. In the resting state, NRF2 binds to its negative regulatory protein Keap1 and is degraded by ubiquitination, maintaining low levels. When stimulated by oxidative stress or activators such as sophora flavescens, NRF2 dissociates from Keap1, translocates to the nucleus, and binds to antioxidant response elements (ARE), initiating the transcriptional expression of a series of downstream phase II detoxifying enzymes and antioxidant proteins.
  The function of sophora flavescens glycoside Research has shown that sophocarpine can effectively activate the NRF2 signaling pathway. It may interfere with the Keap1-NRF2 interaction by modifying cysteine residues on Keap1, thereby stabilizing the NRF2 protein and promoting its nuclear translocation. The activated NRF2 further upregulates the expression of a series of genes with cell protective effects.

• Key downstream target genes and proteins：

  1. NFE2L2/NRF2 This is the core target gene/protein of the pathway itself. Sophora japonica glycoside activates and stabilizes NRF2, initiating the entire antioxidant defense program.
  2. HMOX1 (heme oxygenase-1)This is one of the most important target genes of NRF2. HMOX1 catalyzes the degradation of heme into biliverdin, carbon monoxide, and iron ions. Bilibilin and its reduced product bilirubin are potent endogenous antioxidants. Sophora japonica glycoside significantly induces the expression of HMOX1, which is a key effector molecule for its antioxidant and anti-inflammatory effects.
  3. SOD1 (superoxide dismutase 1, cytoplasmic type) and SOD2 (superoxide dismutase 2, mitochondrial type)These two enzymes are the first line of defense against superoxide anion radicals (O ₂⁻·), converting them into H ₂ O ₂. Sophora japonica glycoside upregulates the expression of SOD through pathways such as NRF2, enhancing the cell's ability to clear superoxide.
  4. CAT (catalase)Responsible for catalyzing the decomposition of H ₂ O ₂ into water and oxygen, it is the main enzyme for removing H ₂ O ₂. Huaijiao glycoside can enhance the activity of CAT.
  5. GPX1 (Glutathione Peroxidase 1)The use of reduced glutathione (GSH) to reduce H ₂ O ₂ and organic peroxides to harmless alcohols and water is another key enzyme that maintains intracellular redox balance. Sophora japonica glycoside can upregulate the expression of GPX1 and promote the synthesis of GSH.

• Interaction with other pathways：
  The antioxidant effect of sophora japonica glycoside does not exist in isolation. The NRF2 pathway has extensive cross-talk interactions with signaling pathways such as NF - κ B, MAPK, and PI3K/Akt. For example, the anti-inflammatory effect produced by the activation of the NRF2/HMOX1 pathway by sophocarpine can inhibit the excessive activation of NF - κ B, thereby synergistically reducing the inflammatory response. In addition, its anti-cancer activity may also be partially derived from regulating the proliferation and apoptosis signals of cancer cells by modulating the redox state.

In summary, sophora flavescens systematically enhances the entire endogenous antioxidant defense network, including SOD, CAT, GPX, and HMOX1, by targeting and activating the "main switch" NRF2. This is the fundamental molecular mechanism for its resistance to oxidative damage and multiple pharmacological activities.

Evaluation of drug properties and pharmacokinetics

Although sophocarpine has shown good 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.

• Absorption, distribution, metabolism, excretion (ADME)：

  • absorb As a glycoside compound, the oral bioavailability of sophoroside may be limited. β - glucosidase in the intestine may hydrolyze it into aglycones (genistein) and glucose, which have higher lipid solubility and may be absorbed. Therefore, sophora flavescens may act in two forms in vivo: prototype and aglycone, which increases the complexity of its pharmacokinetics.
  • distribution As mentioned earlier, its high polarity and TPSA result in low blood-brain barrier permeability, mainly distributed in peripheral tissues and organs.
  • Metabolism Sophora japonica glycoside and its aglycones mainly undergo phase II metabolic reactions in the liver and intestine, such as glucuronidation and sulfation, forming more water-soluble complexes that are excreted through bile and urine.
  • excretion The prototype drug and its metabolites are mainly excreted through the kidneys.

• Challenges and Strategies in Drug Development：

  1. bioavailability Improving oral bioavailability is the main challenge. The strategy includes developing prodrugs (such as esterification modification), using absorption enhancers, or preparing them into novel drug delivery systems such as liposomes, polymer nanoparticles, solid dispersions, etc., to enhance their solubility and intestinal permeability.
  2. Targeted delivery To address the issue of poor blood-brain barrier permeability, if central nervous system diseases need to be treated, it is possible to consider designing nanocarriers targeting the brain (such as modified blood-brain barrier penetrating peptides).
  3. structural optimization Based on the active skeleton of sophoricoside, rational structural modification is the direction of medicinal chemistry research to improve its ADME properties while retaining or enhancing its pharmacological activity.

At present, there are relatively limited research reports on the pharmacokinetics of sophoricoside system. In vivo ADME research and formulation exploration are necessary steps to promote its clinical application.

Clinical application prospects and prospects

Huaijiao glycoside, as a natural active molecule with multiple targets and functions, has shown broad application prospects in the prevention and treatment of various oxidative stress-related diseases.

1. Potential therapeutic areas：

   • cardiovascular disease: It may be used as an adjuvant treatment for atherosclerosis, hypertension and other diseases through antioxidant, anti-inflammatory and protection of vascular endothelial function.
   • Metabolic diseases Oxidative stress is the key pathogenic factor in nonalcoholic fatty liver disease, diabetes and its complications (such as diabetes nephropathy and neuropathy). The NRF2 activation effect of sophocarpine may provide protection.
   • Neurodegenerative diseases Although BBB permeability is poor, its potential in Alzheimer's disease and Parkinson's disease is worth exploring through improved formulation techniques or for preventing indirect effects of peripheral inflammation on the central nervous system.
   • Inflammatory and autoimmune diseases Such as rheumatoid arthritis, inflammatory bowel disease, etc.
   • Cancer chemoprevention As a dietary supplement or functional food ingredient, long-term low-dose use may reduce cancer risk by maintaining the body's redox homeostasis.

2. Research and Development Prospects：

   • In depth mechanism research Further elucidate the precise molecular details of the interaction between sophora flavescens glycoside and Keap1-NRF2, and discover other potential direct targets.
   • Preclinical systematic review Conduct standardized pharmacological, toxicological, and pharmacokinetic system studies to clarify their therapeutic window and safety.
   • Formulation innovation Vigorously develop a new drug delivery system that can overcome its drug weakness.
   • Exploration of combination therapy Research on the combined use of sophora flavescens glycoside and existing drugs (such as chemotherapy drugs and anti-inflammatory drugs) may produce synergistic effects and reduce side effects.
   • Source quality control Optimize the sustainable plant extraction or biosynthesis process of sophora flavescens glycosides to ensure stable supply and uniform quality of raw materials.

Conclusion

Sophora flavescens glycoside is an important research value isoflavone glycoside discovered from traditional Chinese medicine Sophora flowers. It precisely activates the NRF2 signaling pathway, upregulates the expression of key antioxidant enzymes such as HMOX1, SOD, CAT, GPX, and constructs a powerful cellular defense system, effectively combating oxidative damage, and thus deriving multiple pharmacological activities such as anti-inflammatory, anticancer, and immune regulation. Despite facing challenges in terms of bioavailability and target tissue distribution for drug development, these challenges are gradually being transformed into innovative opportunities with the continuous development of modern pharmaceutical chemistry, pharmacology, and molecular biology technologies. In the future, through in-depth basic research, systematic preclinical development, and innovative formulation strategies, sophoricoside is expected to develop from a promising lead compound into an innovative drug or functional health product for the prevention and treatment of oxidative stress-related chronic diseases, fully reflecting the unique value of natural products in modern medicine.