Product name: Cirsimaritin
Synonym name: Scrophulein；Skrofulein；6,7-Dimethoxyscutellarein
Catalogue No.: BP4489
Cas No.: 6601-62-3
Formula: C₁₇H₁₄O₆
Mol Weight: 314.293
Botanical Source: Abrus precatorius L.
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 Cirsimaritin

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

Introduction/Overview

In the vast treasure trove of natural products, flavonoids have attracted much attention for their diverse biological activities and extensive pharmacological effects. Cirsimaritin, as a naturally occurring methoxyflavonoid, has gradually entered the field of researchers in recent years and demonstrated unique pharmacological value. Binjihuang, also known as 5,4 '- dihydroxy-6,7-dimethoxyflavone, is a secondary metabolite with a typical flavonoid core structure. It is widely present in various medicinal plants, such as the Lamiaceae and Asteraceae families. Its name originates from the original species of thistle in the genus Cirsium（Cirsium）It is named "Binjihuang" because of its separation and identification.

The pharmacological activity spectrum of Bin Ji Huang is relatively broad, covering multiple fields such as central nervous system, antiviral, anti-inflammatory, antioxidant, etc. Of particular note is that research has found that astaxanthin can target the benzodiazepine (BZD) site on gamma aminobutyric acid type A (GABAA) receptors with relatively weak affinity, which makes it potentially have anti anxiety, anti depression, and anti seizure effects. Compared with classic benzodiazepines such as diazepam, Binjihuang, as a natural ligand, may have different binding modes and pharmacological effects, providing a new lead compound for the development of novel, low side effect anti anxiety/antidepressant drugs.

In addition, Binjihuang has demonstrated remarkable activity in the field of antiviral therapy. Research has shown that it has a certain inhibitory effect on various viruses, including herpes simplex virus (HSV), human immunodeficiency virus (HIV), etc. Its antiviral mechanism may involve multiple targets, such as myeloperoxidase (MPO), viral DNA polymerase helper protein (UL42), DNA polymerase catalytic subunit (UL54), viral protein ICP27, thymidine kinase (TK), glycoprotein D (gD), as well as host cell chemokine receptors CCR5 and CXCR4. This multi-target characteristic of action gives Bin Ji Huang a potential advantage in combating viral drug resistance.

Despite exhibiting many promising biological activities, the pharmacological potential of Bin Ji Huang as a drug candidate molecule still needs to be comprehensively evaluated. Its molecular weight is moderate (314.2930 Da), lipid water partition coefficient (LogP) is 2.2994, and topological polar surface area (TPSA) is 89.1300 Å ². These physicochemical parameters suggest that it has certain oral absorption potential. However, its poor water solubility (0.0386 mg/mL) and low blood-brain barrier penetration ability may limit its application in certain central nervous system diseases. Preliminary toxicological evaluation shows that Binjihuang has no significant inhibitory effect on hERG potassium channels (hERG inhibition: No), and the Ames test result (0.6) suggests a low genetic toxicity risk, but further verification is needed.

This article aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of Bin Ji Huang, in order to provide comprehensive scientific basis for the in-depth research and development of this natural product.

Chemical structure and physicochemical properties

Cirsimaritin belongs to the flavonoid class of compounds, and its chemical structure has a typical flavonoid nucleus (2-phenylchromenone). Specifically, its chemical name is 5,4 '- dihydroxy-6,7-dimethoxyflavone. The structural features are as follows: the C-5 position of ring A is connected to a hydroxyl group (- OH), and the C-6 and C-7 positions are each connected to a methoxy group (- OCH ∝); The C-4 'position of the B ring is connected to a hydroxyl group. This substitution mode endows Bin Ji Huang with unique physicochemical properties and biological activity.

From the molecular formula, the molecular formula of Binjihuang is C ₁₇ H ₁₄ O ₆, with a molecular weight of 314.2930 g/mol. Its molecular weight is moderate and meets the requirement of molecular weight less than 500 in Lipinski's Rule of Five, which provides a basis for the development of its oral medication. The lipid water partition coefficient (LogP) is an important parameter for measuring the lipophilicity of compounds. The LogP of Binjihuang is 2.2994, indicating its moderate lipophilicity, which is beneficial for transmembrane transport and interaction with biological targets. The topological polar surface area (TPSA) is 89.1300 Å ², which reflects the total surface area of polar atoms (such as oxygen and nitrogen) and their connected hydrogen atoms in the molecule. Generally, compounds with a TPSA of less than 140 Å ² have good oral absorption and intestinal permeability, and the TPSA value of Bin Ji Huang is within this range, indicating that its oral bioavailability may be good.

However, the water solubility of Bin Ji Huang is poor, with a water solubility parameter of only 0.0386 mg/mL. This characteristic may become a challenge in the development of its formulations, as low water solubility often limits the dissolution rate and absorption of drugs in the body. To improve its water solubility, it may be necessary to use formulation techniques such as solid dispersions, nanoparticles, liposomes, or cyclodextrin inclusion complexes.

In terms of stability, Bin Ji Huang, as a flavonoid compound, is relatively stable under acidic conditions, but is prone to degradation under alkaline conditions. In addition, light exposure, high temperature, and oxidative environment may also affect its stability. Therefore, appropriate measures such as light avoidance, low temperature, and oxidation prevention need to be taken during storage and formulation.

Regarding the blood-brain barrier (BBB) penetration ability, existing data indicates that the BBB penetration ability of berberine is relatively low. This characteristic has a dual significance: on the one hand, for antidepressant, anti anxiety, and anticonvulsant activities that require action in the central nervous system, lower BBB penetration may limit their efficacy; On the other hand, for antiviral and anti-inflammatory activities that require peripheral action, lower BBB penetration may reduce central nervous system side effects. How to improve its BBB penetration through structural modification or optimization of drug delivery routes is an important direction for future research.

Plant sources and extraction methods

Binjihuang, as a natural flavonoid compound, is widely present in various medicinal plants, especially in Lamiaceae and Asteraceae plants, where its content is relatively abundant. Common plant sources include:

1. Cirsium plants（Cirsium spp.）Like Little Ji（Cirsium setosum）Da Ji（Cirsium japonicum）Wait, Bin Ji Huang was initially isolated and identified from this genus of plants.
2. Scutellaria baicalensis plants（Scutellaria spp.）Like Scutellaria baicalensis（Scutellaria baicalensis）Half branch lotus（Scutellaria barbata）Wait, these plants are a rich source of flavonoids, among which astaxanthin is one of the active ingredients.
3. Perilla plants（Perilla spp.）Like perilla（Perilla frutescens）The leaves and seeds also contain astaxanthin.
4. Plants of the Elsholtzia genus（Elsholtzia spp.）Like fragrant lotus（Elsholtzia ciliata）Wait.
5. Other plants Like marigold flowers（Calendula officinalis）Sage（Salvia spp.）、 Niuzhi（Origanum vulgare）It has also been reported to contain astaxanthin.

Due to the significant differences in the content of astaxanthin in different plants and its frequent coexistence with other structurally similar flavonoids, it is crucial to choose appropriate plant sources and efficient extraction and separation methods.

extraction method Traditional extraction methods include solvent extraction, such as cold soaking, percolation, or reflux extraction using methanol, ethanol, acetone, or their aqueous solutions. Due to the lipophilicity of Bin Ji Huang, 70% -95% ethanol or methanol is usually selected as the extraction solvent. In order to improve extraction efficiency and selectivity, some modern extraction techniques have been widely applied in recent years, such as ultrasound assisted extraction, microwave-assisted extraction, enzyme assisted extraction, and supercritical fluid extraction. These methods can shorten extraction time, reduce solvent usage, and improve the extraction rate of target compounds.

Separation and purification methods The crude extract obtained from extraction usually contains various impurities, which require further separation and purification to obtain high-purity Bin Ji Huang. Common separation and purification techniques include:

1. Column chromatography method This is the most commonly used method. Common stationary phases include silica gel, polyamide, macroporous adsorption resin (such as D101, AB-8), dextran gel (such as Sephadex LH-20), etc. By selecting appropriate elution systems (such as chloroform methanol, ethyl acetate methanol, etc. in different proportions), effective separation of astaxanthin from other flavonoids can be achieved.
2. Preparation type high-performance liquid chromatography method For high-purity requirements or separation of trace components, preparative HPLC is an efficient method. By optimizing chromatographic conditions (such as stationary phase, mobile phase, flow rate, detection wavelength, etc.), high-purity Bin Ji Huang can be quickly obtained.
3. High-speed countercurrent chromatography This is a chromatographic technique based on the liquid-liquid distribution principle, which does not require the use of a solid stationary phase, avoids irreversible adsorption, and is suitable for the separation of flavonoids.

During the separation process, it is usually necessary to combine thin layer chromatography (TLC) or HPLC for real-time monitoring to determine the elution position of the target compound. Finally, the isolated compound was structurally identified using spectroscopic techniques such as nuclear magnetic resonance (NMR) and mass spectrometry (MS), confirming its identity as astaxanthin.

Pharmacological activity research

Binjihuang, as a multifunctional natural flavonoid, has been studied for its pharmacological activities in multiple fields including central nervous system, antiviral, anti-inflammatory, antioxidant, and anti-tumor.

1. Central nervous system activity

One of the most notable activities of Bin Ji Huang is its effect on the central nervous system. Research has found that Bin Ji Huang can bind to the benzodiazepine site on GABAA receptors with low affinity, thereby exerting its pharmacological effects. GABAA receptors are the main inhibitory neurotransmitter receptors in the central nervous system, and their activation can cause neuronal hyperpolarization, reduce neural excitability, and produce effects such as anti anxiety, sedation, and anticonvulsant.

• Anti anxiety effect Animal experiments have shown that astaxanthin can significantly reduce anxiety like behavior in mice in anxiety models such as elevated cross maze and light dark box. Its mechanism of action is related to the partial activation of GABAA receptors and may not produce significant sedative or muscle relaxant side effects, which is different from classical benzodiazepines such as diazepam.
• Antidepressant effect In depression models such as forced swimming and tail suspension experiments, Binjihuang can significantly shorten the immobility time of mice and exhibit antidepressant like effects. The mechanism may involve regulating the levels of monoamine neurotransmitters such as serotonin and norepinephrine, as well as affecting the function of the hypothalamic pituitary adrenal axis.
• Anticonvulsant effect Binjihuang has a certain protective effect on seizure models induced by chemical convulsants such as pentylenetetrazole and strychnine, which can prolong the latency of seizures and reduce the severity of seizures. Its anticonvulsant effect is closely related to the activation of GABAA receptors.

2. Antiviral activity

Binjihuang also exhibits broad-spectrum activity in the field of antiviral, especially in inhibiting herpes virus and HIV virus.

• Anti herpes simplex virus (HSV) effect In vitro experiments have shown that astaxanthin can inhibit the replication of HSV-1 and HSV-2. The mechanism may involve multiple targets: inhibiting the activity of virus DNA polymerase helper protein UL42 and DNA polymerase catalytic subunit UL54, thereby blocking the synthesis of virus DNA; Inhibit the function of viral protein ICP27 and interfere with the expression of viral genes; Inhibiting the activity of thymidine kinase (TK) and affecting viral nucleotide metabolism; And inhibit the function of virus glycoprotein D (gD), interfere with the virus's adsorption and invasion of host cells.
• Anti human immunodeficiency virus (HIV) effect Binjihuang also has an inhibitory effect on HIV-1 replication. Its potential targets may include: inhibiting the activity of HIV-1 protease (HIV1-PR), thereby preventing the maturation of viral particles; Inhibiting the activity of integrase (INT) and blocking the process of viral DNA integration into the host cell genome; In addition, Binjihuang can also block the entry of HIV virus into target cells by downregulating the expression of chemokine receptors CCR5 and CXCR4 on the host cell surface. This multi-target anti HIV mechanism has potential advantages in addressing HIV drug resistance.

3. Anti inflammatory and antioxidant activity

• anti-inflammatory effect Binjihuang can inhibit the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in macrophages induced by lipopolysaccharide (LPS). The mechanism may be related to the inhibition of the activation of the nuclear factor kappa B (NF - κ B) signaling pathway, thereby downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Binjihuang can also inhibit the release of pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and interleukin-1 β (IL-1 β).
• Antioxidant effect Binjihuang has strong free radical scavenging ability and can effectively scavenge 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) radicals, hydroxyl radicals, and superoxide anion radicals. Its antioxidant activity is closely related to the phenolic hydroxyl groups (C-5 and C-4 'positions) in its molecular structure, which can provide hydrogen atoms, neutralize free radicals, and protect cells from oxidative stress damage.

4. Other activities

In addition to the main activities mentioned above, Binjihuang has also been reported to have anti-tumor, hepatoprotective, hypoglycemic, antibacterial and other effects. For example, Bin Ji Huang can inhibit the proliferation of various cancer cells and induce apoptosis, and its mechanism may be related to regulating the cell cycle and activating apoptotic signaling pathways. In terms of liver protection, Binjihuang can alleviate chemical liver damage, reduce serum transaminase levels, and its effects are closely related to antioxidant and anti-inflammatory activities.

Mechanism of action and molecular targets

The pharmacological activity of Bin Ji Huang is derived from its interactions with various molecular targets. Its mechanism of action exhibits the characteristics of multi-target and multi pathway.

1. Central nervous system target: GABAA receptor benzodiazepine site

The effect of Bin Ji Huang on the central nervous system is mainly attributed to its regulation of GABAA receptors. GABAA receptor is a pentameric ligand gated chloride ion channel with diverse subunit compositions, among which receptors containing the γ 2 subunit are sensitive to benzodiazepines. Benzodiazepine drugs bind to the interface between the alpha and gamma subunits (i.e. the benzodiazepine site), increasing the affinity of GABA for receptors through allosteric regulation, thereby enhancing the opening frequency of chloride ion channels and producing inhibitory effects.

Compared with classic benzodiazepines such as diazepam, Binjihuang has a lower affinity for this site and belongs to partial or weak agonists. This characteristic may result in weaker anti anxiety and anticonvulsant effects, while avoiding side effects such as excessive sedation, muscle relaxation, tolerance, and dependence that may occur with complete agonists. Further research is needed to investigate the selectivity of Binjihuang towards different subtypes of GABAA receptors, which may be the key to its unique pharmacological effects.

2. Antiviral targets

The antiviral activity of Bin Ji Huang involves multiple viral and host targets, reflecting its multi mechanism antiviral characteristics.

• Virus target：

  • UL42 and UL54 UL42 is an auxiliary protein of HSV DNA polymerase, and UL54 is the catalytic subunit of DNA polymerase. Binjihuang may inhibit the activity of these proteins by binding to them, thereby blocking the replication of viral DNA.
  • ICP27 ICP27 is an immediate early protein of HSV, involved in transcriptional regulation of viral genes and nuclear export of mRNA. Binjihuang may interfere with the function of ICP27 and inhibit the expression of viral genes.
  • TK Thymidine kinase is a key enzyme in viral nucleotide metabolism, responsible for phosphorylating thymidine to thymidine acid. Binjihuang may inhibit TK activity, thereby affecting the synthesis of viral DNA.
  • gD Glycoprotein D is the main glycoprotein on the envelope of HSV virus, responsible for binding to host cell receptors and mediating virus invasion. Binjihuang may block virus adsorption to host cells by binding to gD.
  • HIV1-PR and INT HIV-1 protease is responsible for cleaving viral precursor proteins into mature proteins, while integrase is responsible for integrating viral DNA into the host genome. Binjihuang may inhibit the activity of these two enzymes, thereby suppressing the replication and integration of HIV.

• Host target：

  • CCR5 and CXCR4 CCR5 and CXCR4 are the two main chemokine receptors required for HIV-1 to enter target cells. Binjihuang may block the entry of HIV virus into cells by downregulating the expression of these receptors or directly binding to them.

3. Anti inflammatory and antioxidant mechanisms

• NF - κ B signaling pathway Binjihuang can inhibit the activation of NF - κ B. In the resting state, NF - κ B binds to the inhibitory protein I κ B and exists in an inactive form in the cytoplasm. When stimulated by LPS, TNF - α, etc., I κ B is phosphorylated and degraded, releasing NF - κ B, which enters the nucleus and initiates transcription of various inflammation related genes (such as iNOS, COX-2, TNF - α, IL-6, etc.). Binjihuang may exert anti-inflammatory effects by inhibiting the phosphorylation of I κ B or directly binding to NF - κ B, blocking this signaling pathway.
• free radical scavenging The phenolic hydroxyl groups (C-5 and C-4 'positions) in the molecule of Binjihuang can provide hydrogen atoms, which combine with free radicals to form stable semiquinone free radicals, thereby interrupting the chain reaction of free radicals and exerting antioxidant effects.

Evaluation of drug properties and pharmacokinetics

To develop Bin Ji Huang into a clinical drug, a comprehensive evaluation of its pharmacological properties, including physicochemical properties, pharmacokinetic characteristics, and safety, is required.

1. Physical and chemical properties and drug like properties

As mentioned earlier, the molecular weight (314.2930 Da), LogP (2.2994), and TPSA (89.1300 Å ²) of Binjihuang all comply with the "five rules of drug class", indicating its good oral absorption potential. However, its poor water solubility (0.0386 mg/mL) is the main factor limiting its oral bioavailability. In addition, its blood-brain barrier penetration ability is relatively low, which may limit the activity of the central nervous system.

2. Pharmacokinetic characteristics

At present, there is insufficient systematic research on the pharmacokinetics of Platycodon grandiflorus. However, based on its physicochemical properties and studies of similar compounds, possible pharmacokinetic characteristics can be inferred

• absorb The absorption of astaxanthin in the intestine may be limited by its low water solubility. In addition, as a flavonoid compound, it may undergo first pass metabolism, including phase II metabolic reactions such as glucuronidation and sulfation in the intestine and liver, resulting in lower oral bioavailability. Combined use with certain drugs (such as piperine) may increase their bioavailability by inhibiting metabolic enzymes.
• distribution Due to its moderate lipophilicity, astaxanthin may be widely distributed in tissues. But its lower BBB penetration ability may result in lower concentrations in the central nervous system.
• Metabolism Binjihuang is mainly metabolized in the liver and may undergo reactions such as O-demethylation, hydroxylation, glucuronic acid binding, and sulfate binding. Its metabolites may still have biological activity.
• excretion Binjihuang and its metabolites are mainly excreted through bile and urine.

3. Safety evaluation

The preliminary safety evaluation results showed that Binjihuang had no significant inhibitory effect on hERG potassium channels (hERG inhibition: No), indicating a low risk of cardiac toxicity. The Ames test result (0.6) indicates a low risk of genetic toxicity, but this value may indicate slight mutagenicity under specific conditions and requires more comprehensive genetic toxicity tests (such as in vivo micronucleus test, chromosome aberration test) to confirm. In addition, systematic toxicological studies on acute toxicity, subchronic toxicity, reproductive toxicity, etc. are needed to comprehensively evaluate their safety.

Clinical application prospects and prospects

Binjihuang, as a natural flavonoid with multi-target activity, has shown potential clinical application prospects in multiple therapeutic fields.

1. Diseases of the central nervous system

Binjihuang, as a weak agonist of GABAA receptors, is expected to be developed as a novel anti anxiety and antidepressant drug. Compared with existing benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), it may have the advantages of fast onset and fewer side effects (such as no sedation, muscle relaxation, dependence, and sexual dysfunction). However, its lower BBB penetration is an obstacle that needs to be overcome. In the future, its BBB penetration ability can be improved through structural modification (such as introducing lipophilic groups or prodrug design) or the use of novel drug delivery systems (such as nanoparticles, liposomes, nasal delivery, etc.), thereby enhancing the efficacy of the central nervous system.

2. Antiviral therapy

The broad-spectrum antiviral activity of Bin Ji Huang, especially its inhibitory effect on HSV and HIV, makes it potential for development as an antiviral drug. Its multi-target mechanism of action is beneficial for reducing the development of viral drug resistance. For HSV infection, binjixanthin can be used as a candidate drug for local medication (such as cream, gel) or oral medication. For HIV infection, berberine can be used as an adjuvant drug in combination antiretroviral therapy (cART) to enhance the effectiveness of existing therapies by inhibiting virus replication and blocking virus entry. But further research is needed to determine the selectivity index between its antiviral activity and cytotoxicity to ensure its safety.

3. Inflammatory related diseases

The anti-inflammatory and antioxidant activities of Bin Ji Huang make it potentially valuable in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, asthma, etc. Its multi-target anti-inflammatory mechanism may have better efficacy and lower side effects than single target anti-inflammatory drugs.

4. Future research directions

Although some progress has been made in the study of astaxanthin, there are still many issues that need to be addressed:

1. In depth pharmacokinetic research A systematic study is needed to investigate the absorption, distribution, metabolism, and excretion processes of Bin Ji Huang in animals and humans, clarify its metabolites and their activities, and provide a basis for the design of clinical dosing regimens.
2. Research on Structural Optimization and Structure Performance Relationship By synthesizing a series of structurally similar compounds of Platycodon grandiflorus, studying the effects of different substituents on their biological activity, selectivity, pharmacokinetic properties, and toxicity, and searching for lead compounds with stronger activity, higher selectivity, and better drug properties.
3. In depth study of the mechanism of action Using molecular docking, surface plasmon resonance, X-ray crystallography and other techniques, clarify the specific binding mode and interaction details of Binjihuang with GABAA receptors, viral proteins and other targets.
4. Formulation research Develop appropriate formulation technologies, such as solid dispersions, nanoemulsions, liposomes, phospholipid complexes, etc., to address the issues of poor water solubility and low BBB penetration, in order to improve their bioavailability and targeting.
5. Toxicological evaluation of the system Conduct comprehensive preclinical toxicology studies, including acute toxicity, long-term toxicity, reproductive toxicity, genetic toxicity, etc., to provide assurance for the safety assessment of clinical trials.
6. clinical trial After completing sufficient preclinical research, conduct clinical trials to verify its efficacy and safety in humans.

Conclusion

Binjihuang, as a naturally occurring methoxy flavonoid, occupies a place in the field of natural product pharmacology due to its unique chemical structure and diverse pharmacological activities. It can act on GABAA receptors with weak affinity, exerting anti anxiety, anti depression, and anti seizure effects, as well as inhibiting the replication of various viruses through multi-target mechanisms. At the same time, it also has significant anti-inflammatory and antioxidant activities. These characteristics make it a highly promising natural drug lead compound for development.

However, the pharmacological properties of Binjihuang still face challenges, especially its low water solubility and low blood-brain barrier penetration ability, which limit its clinical application. Future research should focus on structural optimization, formulation innovation, and in-depth pharmacokinetic and toxicological evaluation to overcome these obstacles. With the continuous deepening of research, Bin Ji Huang and its derivatives are expected to play an important role in the treatment of central nervous system diseases, viral infections, and inflammation related diseases, and contribute to human health. The research road of Binjihuang from natural products to innovative drugs is still long, but the prospects are bright.