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Product name: 5-O-Demethylnobiletin
Synonym name: 5-Hydroxy-3′,4′,6,7,8-pentamethoxyflavone
Catalogue No.: BP0088
Cas No.: 2174-59-6
Formula: C20H20O8
Mol Weight: 388.372
Botanical Source: Citrus reticulata Blanco
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:
5-O-Demethylnobiletin has anti-inflammatory activity, it may act through a direct inhibition of 5-LOX, without affecting the expression of COX-2.
References:
Planta Med. 2006 Feb;72(2):136-42.
Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum.
METHODS AND RESULTS:
We have studied the effect of 5-O-Demethylnobiletin( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neutrophils, but did not reduce the expression of cyclooxygenase-2 (COX-2) in murine RAW 264.7 macrophages.
CONCLUSIONS:
These experimental results suggest that 1 may act through a direct inhibition of 5-LOX, without affecting the expression of COX-2.
HPLC of 5-O-Demethylnobiletin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
100.8600
3.1200
3.1200
Low
null
No
No
No
Unknown
No
Unknown
No
Demethyl demethylnobiletin (5-O-Demethylnobiletin, CAS No.: 2174-59-6) is a polymethoxyflavonoid compound, mainly isolated from the tangerine peel of citrus species. As an important member of the flavonoid family, desmethyl Chuanchenretin, due to its unique chemical structure and remarkable biological activity, has attracted widespread attention in the field of natural product pharmacology in recent years. Especially in terms of anti-inflammatory effects, demethylated chenretin exhibits excellent activity, selectively inhibiting 5-lipoxygenase (5-LOX) without affecting cyclooxygenase-2 (COX-2) expression. This characteristic gives it potential application value in the treatment of inflammation-related diseases. In addition, demethylated chenzetin is associated with molecular targets for various diseases such as endometriosis, suggesting it may play an important role in drug development for gynecological diseases.
This paper systematically reviews the chemical structure and physicochemical properties of desmethyl Chuanchenebin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its potential clinical prospects, it aims to provide scientific basis and theoretical support for in-depth research and drug development of this natural product.
Demethyl Chuanchenepin belongs to the polymethoxyflavonoid class of compounds, with a molecular formula of C21H20O7 and a molecular weight of 388.37. Its core structure is a flavonoid backbone, characterized by demethylation at the 5 hydroxyl group positions, forming 5-hydroxy-substituted polymethoxyflavonoids. The compound has a LogP value of about 3.12, showing moderate lipid solubility, which is beneficial for cell membrane penetration and bioavailability. Its topological pole surface area (TPSA) is 100.86 Ų, indicating a good balance between polarity and nonpolarity, making it suitable for interacting with various biological targets.
Demethyl Chuanchenepepin contains eight hydrogen bond receptors, indicating that it may form stable complexes through hydrogen bonds when binding to proteins. Its low blood-brain barrier permeability suggests that this compound mainly acts on peripheral tissues, reducing potential side effects in the central nervous system. Additionally, desmethyl chenepepin carries low risks of hepatotoxicity and cardiotoxicity, and does not inhibit hERG channels, demonstrating good safety profiles.
Demethylated citrus is mainly found in the peel of citrus plants, especially Citrus reticulata Blanco and its related varieties. As a traditional Chinese medicinal material, Sichuan tangerine peel has long been used to regulate the spleen and stomach, regulate qi, and resolve phlegm. Its abundant polymethoxyflavonoid components provide important natural compound resources for pharmacological research.
Common methods for extracting demethylated Chuanchenebin include solvent extraction, liquid-liquid partitioning, and chromatographic separation techniques. Generally, ethanol or methanol is used as extraction solvents, and extraction efficiency is improved through ultrasound-assisted extraction or reflux extraction. After concentration, the extract is separated and purified using silica gel column chromatography or high-performance liquid chromatography (HPLC). In recent years, supercritical fluid extraction and membrane separation technologies have also been applied to improve extraction purity and yield. The purified demethylated chenepein is identified through mass spectrometry and nuclear magnetic resonance (NMR) methods to ensure the compound's purity and structural accuracy.
The pharmacological activity of demethylated chenzetin mainly focuses on anti-inflammatory effects, but it also involves multiple potential biological functions such as antioxidant, antitumor, and neuroprotective effects.
Numerous in vitro and in vivo studies have shown that demethylated chenpetin has significant anti-inflammatory effects. Its main mechanism is direct inhibition of 5-lipoxygenase (5-LOX) activity, with an IC50 value of about 0.1 μM, demonstrating strong enzyme inhibition ability. 5-LOX is a key enzyme in leukotriene biosynthesis, mediating the production of the inflammatory mediator leukotriene B4 (LTB4), which plays an important role in chemotactic and activating the inflammatory response. Demethylated chenretin significantly reduces LTB4 formation in rat neutrophils by inhibiting 5-LOX, thereby alleviating inflammatory responses.
Additionally, desmethyl chenetin can inhibit the release of elastase in human neutrophils, with an IC50 of about 0.35 μM, reducing tissue damage and inflammation spread. Notably, this compound had no significant effect on COX-2 expression, avoiding the gastrointestinal side effects commonly seen with traditional nonsteroidal anti-inflammatory drugs (NSAIDs).
In addition to anti-inflammatory effects, research on desmethyl Chuanchenetin's antioxidant, antitumor, and neuroprotective effects has also increased. Its polymethoxy structure gives it excellent free radical scavenging ability, helping to reduce cell damage related to oxidative stress. In tumor models, desmethyl Chuanchenetin demonstrated the potential to inhibit cancer cell proliferation and induce apoptosis, especially in certain hormone-related tumors. In terms of neuroprotective effects, preliminary studies suggest it may slow the progression of neurodegenerative diseases by regulating neuroinflammatory and oxidative stress pathways.
The main mechanism of action of demethylated chenretin is to directly inhibit the activity of 5-LOX enzyme, blocking the synthesis of leukotriene inflammatory mediators, thereby exerting anti-inflammatory effects. As a key enzyme in inflammatory responses, 5-LOX's activity regulation is crucial for the generation of mediators such as leukotriene B4 (LTB4). LTB4 not only promotes the chemotactic and activation of neutrophils, but also participates in the pathological processes of various inflammatory diseases.
In disease models such as endometriosis, demethylated chaffenzetin is potentially associated with multiple molecular targets, including monoamine oxidase A (MAOA), estrogen receptor β (ESR2), ATP cassette transporter B1 (ABCB1), DNA repair enzyme APEX1, ATP cassette transporter G2 (ABCG2), xanthine oxidase (XDH), estrogen receptor α (ESR1), adenosine receptor A3 (ADORA3) and telomerase reverse transcriptase (TERT), among others. These targets involve multiple signaling pathways including hormone regulation, apoptosis, oxidative stress, and drug transport, suggesting that demethylated chenetein may exert therapeutic effects through multi-target synergistic regulation.
Additionally, demethylated chenretin had no significant effect on COX-2 expression, indicating that its anti-inflammatory mechanism differs from traditional NSAIDs, offering the advantage of selective inhibition of 5-LOX and reducing the risk of side effects caused by COX-2 inhibition.
Demethyl Chuanchenepin exhibits relatively ideal drug development. Its molecular weight is 388.37, complying with Lipinski's "drug similarity rule," and a LogP value of 3.12 indicates moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. TPSA was 100.86 Ų, indicating moderate polarity that facilitates binding to target proteins.
In terms of safety, desmethyl chenetin carries low risks of hepatotoxicity and cardiotoxicity, and does not inhibit hERG channels, reducing safety risks such as arrhythmias. The blood-brain barrier has low permeability, reducing the risk of central nervous system toxicity, but also limiting its therapeutic potential for central nervous system diseases. Ames-induced mutagenic test results are still unclear, and further tests are needed to verify its genotoxicity.
Pharmacokinetic studies show that demethyl Chuanchenebepin is well absorbed orally, but its metabolic pathways and bioavailability still require systematic study. Preliminary data suggest that this compound may be widely metabolized by liver metabolic enzymes, and the activity and safety of these metabolites still require further investigation. In the future, through structural modification and formulation optimization, it is expected to improve its pharmacokinetic performance and enhance its clinical application value.
Demethylated Chuanchenetin, as a polymethoxyflavonoid, shows broad application prospects in the treatment of inflammatory diseases, especially endometriosis and other gynecological conditions, thanks to its selective inhibition of 5-LOX's anti-inflammatory mechanism. The pathological mechanism of endometriosis is complex, involving hormonal imbalance, inflammatory responses, and apoptosis. Demethylated chenetin is expected to become a novel, safe and effective therapeutic candidate drug through multi-target regulation.
Moreover, its antioxidant and antitumor activities make its applications possible in fields such as oncology and neurodegenerative diseases. In the future, combining modern drug design technologies to optimize its structure and formulations, and improve bioavailability and targeting, will help promote the clinical translation of demethylated chenepepin into clinical practice.
However, clinical research on demethylated chenretin is still in its early stages and lacks systematic clinical trial data. In the future, clinical evaluation of pharmacokinetics, safety, and efficacy should be strengthened, and indications and medication regimens should be clarified. At the same time, in-depth analysis of its molecular mechanisms and mechanisms of action will provide theoretical support for its clinical application.
Demethyl Chuanchenebin, a polymethoxyflavone derived from citrus plants, has become a hot topic in natural product pharmacology research due to its remarkable anti-inflammatory activity and good safety. Its unique mechanism of selectively inhibiting 5-LOX without affecting COX-2 expression provides new ideas for the development of novel anti-inflammatory drugs. Combined with its potential effects on various disease-related targets, demethylated chenzetin holds significant application prospects in the treatment of complex diseases such as endometriosis.
In the future, further systematic pharmacokinetics and clinical studies are needed to optimize its druggability and efficacy evaluation, and promote demethylated chaffenetin from the laboratory to clinical application. With further research, desmethyl Chuanchenebin is expected to become an important representative in the development of natural product drugs, bringing new breakthroughs in the treatment of inflammation and related diseases.
Shenshuai
Wenjing
Hedandan
