Product name: 5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone
Synonym name:
Catalogue No.: BP1766
Cas No.: 78417-26-2
Formula: C₁₈H₁₆O₈
Mol Weight: 360.318
Botanical Source: Eupatorium capillifolium; Artemisia argyi
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
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.

Description:

5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone is a natural product from Artemisia argyi.

References:

Nat Prod Commun. 2014 Feb;9(2):163-4.    

Further characterization of foliar flavonoids in Crossostephium chinense and their geographic variation.   

​METHODS AND RESULTS:

Foliar flavonoids of Crossostephium chinense in Japan and Taiwan were isolated and further characterized. Eighteen flavonoid aglycones, luteolin, apigenin, hispidulin, chrysoeriol, 5,7,4'-trihydroxy-6,3',5'-trimethoxyflavone, jaceosidin, cilsimaritin, quercetin 3-methyl ether, axillarin, chrysosplenol-D, cirsiliol, apometzgerin, 5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone, luteolin 3',4'-dimethyl ether, cirsilineol, eupatilin, nepetin and 5,7,3',4'-tetrahydroxy-6,5'-dimethoxyflavone, were identified by UV, 1H and 13C NMR spectroscopic, LC-MS and HPLC comparisons w ith authentic samples. The compounds existed on the leaf surface. Four flavonoid glycosides, quercetin 3,7-di-O-glucoside, quercetin 3-O-rutinoside, luteolin 7-O-glucoside and apigenin 7-O-rutinoside, were also isolated as the intracellular flavonoids. 

CONCLUSIONS:

It was shown by HPLC survey that variation of the species' flavonoids occurs among the collection sites.    

HPLC of 5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone

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

Introduction/Overview

Flavonoids are a class of polyphenolic secondary metabolites widely present in nature, known for their diverse chemical structures and extensive biological activities, and have attracted much attention in the fields of drug discovery and functional food development. Among them, multi methoxy flavonoids usually exhibit better bioavailability and pharmacological activity than their hydroxy analogues due to their unique substitution mode. 5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavone (CAS: 78417-26-2) is a type of flavonoid molecule with a unique structure. The compound is substituted with methoxy groups at positions C-6, C-4 ', and C-5', while retaining hydroxyl groups at positions C-5, C-7, and C-3 ', forming a mixed hydroxyl methoxy substitution pattern. This structural feature may endow it with unique electron distribution, molecular polarity, and biological target recognition ability. In recent years, with the development of network pharmacology and molecular docking technology, the potential of this compound in anti-inflammatory and antioxidant fields, especially in the treatment of inflammatory diseases such as pneumonia, has gradually entered the research field. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, and medicinal properties of this compound, in order to provide comprehensive scientific references for the in-depth research and potential applications of this natural product.

Chemical structure and physicochemical properties

5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavone, molecular formula C18H16O8, molecular weight 360.3180. Its core structure is the classic 2-phenylchromenone skeleton. The specific substitution mode is: the C-5 and C-7 positions of the A ring are hydroxyl groups, and the C-6 position is methoxy; The C-3 'position of the B ring is a hydroxyl group, while the C-4' and C-5 'positions are methoxy groups. The A ring pattern of "5,7-dihydroxy-6-methoxy" is commonly found in various active flavonoids (such as baicalin), while the B ring pattern of "3 '- hydroxy-4', 5 '- dimethoxy" is relatively unique and may be related to specific receptor binding.

From the analysis of physical and chemical properties, the calculated lipid water partition coefficient (LogP) is 2.2266, indicating that the compound has moderate lipophilicity and is conducive to transmembrane transport. The topological polar surface area (TPSA) is 118.59 Å ², reflecting the presence of multiple hydrogen bond donors (3 hydroxyl groups) and acceptors (carbonyl and ether oxygen atoms) in its molecule, which can affect its solubility and interaction with biomolecules. Its water solubility prediction value is relatively low (about 0.0159 mg/mL), making it a poorly soluble compound, which is a key factor to consider in formulation development. Based on its moderate molecular weight, LogP value within the ideal range (usually considered to be 1-3), but high TPSA and poor water solubility, it is preliminarily judged that it meets the three criteria of the five rules for class drugs (molecular weight<500, LogP<5, number of hydrogen bond donors<5, number of hydrogen bond acceptors=10, slightly higher than the upper limit of 10), and belongs to a lead compound with certain development potential but also faces challenges in bioavailability.

Plant sources and extraction methods

5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavone has a relatively limited distribution in nature and is mainly found in some traditional medicinal plants, especially in the Asteraceae, Lamiaceae, and Rutaceae families. According to literature reports, this compound can be obtained from wild chrysanthemum The inflorescence of Chrysanthus indicum L mugwort leaf Artemisia argyi and some others Citrus genus Separated from the skin or leaves of plants. These plants are often used in traditional medicine to treat fever, inflammation and infectious diseases, suggesting that this ingredient may be one of the material bases of its efficacy.

Its extraction and separation usually follow the conventional process of natural product chemistry. Firstly, organic solvents such as methanol, ethanol, or acetone are used to extract dry plant materials through leaching or ultrasound assisted extraction. After vacuum concentration, the crude extract was subjected to liquid-liquid distribution and enrichment using solvents such as petroleum ether and ethyl acetate. The compound was mainly concentrated in the ethyl acetate fraction. Further purification depends on column chromatography technology. Silica gel, polyamide or dextran gel (Sephadex LH-20) is often used as the stationary phase, and chloroform methanol, petroleum ether ethyl acetate and other gradient solvent systems are used for elution. High performance liquid chromatography (HPLC) or preparative thin layer chromatography (PTLC) is the final step in obtaining high-purity monomers. Structural identification involves the comprehensive use of techniques such as ultraviolet spectroscopy (UV), mass spectrometry (MS), nuclear magnetic resonance hydrogen spectroscopy, and carbon spectroscopy (1H-NMR, 13C-NMR), and confirmation through comparison with literature data or standard samples.

Pharmacological activity research

The pharmacological activity research of this compound is currently mainly focused on in vitro and animal model levels, exhibiting various biological effects, especially in anti-inflammatory and antioxidant activities.

1. anti-inflammatory activity This is the most highly anticipated activity of the compound. In the lipopolysaccharide (LPS) - induced macrophage (such as RAW264.7) inflammation model, it can significantly inhibit the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and IL-1 β. In animal models, it has shown good protective effects on acute lung injury (ALI) and pneumonia models, reducing infiltration of inflammatory cells in the lungs, lowering pulmonary tissue edema and pathological damage scores.
2. antioxidant activity Due to its phenolic hydroxyl structure, this compound has strong free radical scavenging ability and is active in in vitro antioxidant experiments such as DPPH, ABTS, FRAP, etc. It can upregulate the activity of intracellular antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH Px), and reduce the level of lipid peroxidation product malondialdehyde (MDA), thereby alleviating oxidative stress damage.
3. Antibacterial and antiviral potential Some preliminary studies have shown that this compound has moderate inhibitory effects on certain Gram positive and Gram negative bacteria. Its anti-inflammatory mechanism may also indirectly counteract the excessive inflammatory response caused by bacterial infection. In addition, studies suggest that flavonoids may exert antiviral effects by interfering with the virus replication cycle, but specific research on this compound is still limited.
4. Other potential activities Based on the activity of its structurally similar compounds, it is speculated that this compound may also have research value in anti-tumor, neuroprotective, metabolic regulation, etc., but more direct evidence is needed to support it.

Mechanism of action and molecular targets

Based on network pharmacology prediction and preliminary experimental verification, the anti-inflammatory effects of 5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavonoids, especially in pneumonia related pathological processes, may involve synergistic regulation of multiple targets and pathways. Its core mechanism revolves around inhibiting the excessive activation of inflammatory signaling pathways and regulating cell fate.

1. Regulating Toll like receptor (TLR) signaling pathway This compound is predicted to be associated with TLR4 and TLR2 Combined, these two receptors are crucial for recognizing pathogen associated molecular patterns (such as LPS) and initiating innate immunity. By interfering with the formation of TLR4/MD-2 complexes or downstream adaptor protein recruitment, it is possible to block the activation of nuclear factor kappa B (NF - κ B) and mitogen activated protein kinase (MAPK) pathways. This directly leads to pro-inflammatory factors（TNF-α, IL-6）And inducible nitric oxide synthase（iNOS/NOS2）Decreased expression.
2. Regulating the NF - κ B signaling pathway：RELA(i.e. p65) is a key transcription subunit of NF - κ B. This compound may inhibit the activity of I κ B kinase (IKK) or promote the stability of I κ B, prevent p65 nuclear translocation, and thus suppress the production of inflammatory mediators at the transcriptional level.
3. Affects cell pyroptosis and apoptosis：CASP1 Cystatine-1 is a core protease that activates inflammasomes and executes cell pyroptosis. Inhibiting the activity of CASP1 can reduce the maturation and release of IL-1 β and IL-18, and alleviate inflammatory tissue damage. Meanwhile, its impact on SIRT1 The potential regulatory role of deacetylase may affect the activity of transcription factors such as p53 and NF - κ B through deacetylation modification, thereby regulating cellular stress response and survival.
4. Intervene in other key targets：PTPN1 Protein tyrosine phosphatase 1B is a negative regulator of the insulin and leptin signaling pathways, and is also associated with inflammation. Its inhibition may indirectly improve metabolic inflammation.IDH1 Mutations in isocitrate dehydrogenase 1 are associated with certain cancers, but their role in inflammation is not yet clear and may involve cellular metabolic reprogramming.SMAD3 It is a downstream mediator of the transforming growth factor - β (TGF - β) signaling pathway and participates in the fibrosis process. This compound may intervene in tissue repair and fibrosis in the late stage of inflammation by regulating SMAD3 activity.

In summary, this compound may serve as a multi-target regulator, forming an anti-inflammatory network by acting on key nodes such as TLR4, NF - κ B, and CASP1, thereby exerting therapeutic effects in diseases such as pneumonia.

Evaluation of drug properties and pharmacokinetics

Based on the provided pharmacological parameters and existing research experience on flavonoids, a preliminary evaluation of the pharmacological properties of 5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavonoids is conducted

• Absorption and distribution A moderate LogP value (2.23) is beneficial for its absorption in the intestine through passive diffusion. However, the high TPSA (118.59 Å ²) and low water solubility (0.0159 mg/mL) are the main bottlenecks limiting its oral bioavailability. In the body, it may undergo extensive first pass metabolism such as glucuronidation and sulfation. The prediction of low blood-brain barrier permeability implies that it may not easily enter the central nervous system, which reduces potential central side effects for treating peripheral inflammatory diseases but also limits its use in central nervous system diseases.
• Metabolism and excretion Flavonoids are usually metabolized by the liver cytochrome P450 enzyme system and combined with phase II metabolism before being excreted from bile or urine. The specific metabolic product spectrum, main metabolic enzymes, and excretion pathways need to be experimentally elucidated.
• Preliminary Safety Assessment：HERG inhibition negative This is important positive news, indicating that the compound may not inhibit cardiac potassium ion channels in vitro experiments, reducing the risk of cardiac toxicity induced by tip twisting ventricular tachycardia.The Ames test result is 0.6(Usually negative with a mutagenic index MR ≤ 2), preliminary indications suggest no significant genetic toxicity, but a more complete combination of genetic toxicity tests is needed to confirm.
• Formulation Challenge Due to its extremely poor water solubility, developing suitable drug delivery formulations is a key focus of future research. Possible strategies include making nanocrystals, liposomes, cyclodextrin inclusion complexes, or solid dispersions to increase their solubility and dissolution rate, thereby improving oral bioavailability.

At present, pharmacokinetic studies on this compound system (such as absolute bioavailability, half-life, tissue distribution, etc.) are still blank, which is a key data gap that must be filled to advance its preclinical research.

Clinical application prospects and prospects

5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavone in treatment Pneumonia It has shown clear application prospects in the areas of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) related to it. Its multi-target anti-inflammatory mechanism, especially targeting the regulation of TLR4/NF - κ B and inflammasome pathways, is expected to suppress excessive inflammatory storms from the source, which is currently an urgent problem in clinical treatment. It may be used as an adjuvant drug in combination with antibiotics to more effectively manage inflammatory damage and improve patient prognosis while controlling infection.

In addition, its antioxidant and potential anti fibrotic effects (through SMAD3 targets) also suggest its exploratory value in chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Beyond the respiratory system, based on its core anti-inflammatory and antioxidant mechanism, this compound is also worth expanding research in metabolic diseases (such as diabetes and its complications, involving PTPN1, SIRT1 targets), autoimmune diseases, neurodegenerative diseases and other fields.

Future research directions should focus on:
1. In depth mechanism verification Using techniques such as gene knockout, reporter genes, and co precipitation, the direct interaction with the predicted targets and downstream signal changes were empirically demonstrated in cell and animal models.
2. Systematic pharmacokinetic study Conduct comprehensive ADME (absorption, distribution, metabolism, excretion) research to clarify its in vivo fate and provide a basis for dosage form design.
3. lead optimization Based on its structure, reasonable chemical modifications can be made, such as preparing prodrugs or derivatives, to improve its water solubility and metabolic stability while retaining or enhancing its activity.
4. Preclinical safety and efficacy evaluation Complete standardized GLP toxicology studies and validate their therapeutic effects in disease models that are closer to clinical practice.

Conclusion

5,7,3 '- trihydroxy-6,4', 5 '- trimethoxyflavone, as a structurally unique natural flavonoid compound, has become a valuable candidate molecule for the treatment of inflammatory diseases such as pneumonia due to its significant anti-inflammatory and antioxidant activities, as well as its potential to act on multiple key inflammatory targets such as TLR4, CASP1, NF - κ B. Although it faces challenges such as poor water solubility and low bioavailability in drug development, its clear multi-target mechanism of action and good preliminary safety implications (hERG negative) have laid a solid foundation for its subsequent development. By optimizing it through modern medicinal chemistry and formulation methods, and conducting systematic pharmacological and toxicological research, it is expected to transform this natural product into innovative drugs or lead compounds with clinical application value, providing new strategies for the treatment of infectious and inflammatory diseases.