Product name: Eupatorin-5-methyl ether
Synonym name: 3'-Demethylsinensetin; 3'-Desmethylsinensetin；3'-Hydroxy-4',5,6,7-tetramethoxyflavone
Catalogue No.: BP5055
Cas No.: 21764-09-0
Formula: C19H18O7
Mol Weight: 358.346
Botanical Source:
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.
CNMR of Eupatorin-5-methyl ether
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Natural products, as an important source of drug discovery, hold an irreplaceable position in modern pharmacological research. Flavonoids, due to their diverse bioactivity and relatively good safety, have become a hot topic in pharmacological research of natural products. Eupatorin-5-methyl ether (TMF) is a flavonoid compound isolated from the medicinal herb Orthosiphon stamineus. In recent years, it has attracted widespread attention due to its significant anti-inflammatory activity and potential pharmacological effects. TMF can effectively inhibit nitric oxide (NO) production, with an IC50 value of 5.5 μM, demonstrating strong anti-inflammatory potential. Additionally, TMF has good drug compatibility and druggability parameters, demonstrating high clinical development potential.
This paper aims to systematically review the chemical structure and physicochemical properties of TMF, plant origins and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and to explore its prospects and challenges in clinical application, providing a theoretical foundation and reference for subsequent drug development and mechanistic studies.
Geranogenogenol-5-methyl ether (CAS No.: 21764-09-0) belongs to the flavonoid class of compounds, with a molecular formula of C20H18O6 and a molecular weight of 358.3460. Its structural feature is a typical flavonoid backbone, containing multiple hydroxyl and methoxy substituents, especially the methyl etherification modification at position 5, which gives it unique physicochemical properties and biological activity.
In terms of physicochemical properties, TMF has a LogP value of 2.5174, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 87.36 Ų, indicating moderate molecular polarity, which can balance water and lipid solubility, contributing to improved bioavailability. Its low water solubility (0.0051 mg/mL) may limit its oral absorption, but its leaching performance can be improved through appropriate formulation techniques. TMF also demonstrates a high blood-brain barrier penetration capacity, suggesting its potential role in central nervous system diseases. A negative hERG channel inhibition test indicates a low risk of cardiotoxicity. The Ames test result was 0.6, indicating a low genotoxicity risk and relatively good safety.
Osteosiphon 5-methyl ether is mainly isolated from Orthosiphon stamineus, a plant in the Lamiaceae family. Semidentium is widely distributed in Southeast Asia and is a commonly used traditional herbal material, possessing multiple effects including diuretic, anti-inflammatory, antibacterial, and antioxidant properties. The leaves and stems of this plant are the main accumulation sites for TMF.
Common methods for extracting TMF include solvent extraction and chromatographic separation. Generally, methanol or ethanol is used as the extraction solvent, and crude extracts are obtained by reflux extraction or ultrasound-assisted extraction. Subsequently, silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification. The purified TMF is structured by methods such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR). In recent years, supercritical fluid extraction and membrane separation technologies have also been used to improve extraction efficiency and purity, providing technical support for large-scale TMF preparation.
Pharmacological activity research on TMF mainly focuses on its anti-inflammation, antioxidant, anti-tumor, and neuroprotective aspects.
TMF exerts anti-inflammatory effects by significantly inhibiting NO production. NO is an important mediator in inflammatory responses; excessive production can lead to tissue damage and chronic inflammation. The IC50 of TMF is 5.5 μM, demonstrating strong inhibition capability. In vitro studies have shown that TMF can inhibit the expression of induced nitric oxide synthase (iNOS) in macrophages, reducing the release of inflammatory mediators. Additionally, TMF can inhibit the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor α (TNF-α), further exerting anti-inflammatory effects.
TMF has the ability to scavenge free radicals and can reduce oxidative stress levels. Its flavonoid framework structure gives it strong electron donor capabilities, enabling it to effectively capture reactive oxygen species (ROS) and nitrogen radicals, protecting cells from oxidative damage. Multiple in vitro antioxidant experiments, such as DPPH radical scavenging assays and ABTS methods, have confirmed the antioxidant potential of TMF.
Preliminary studies have shown that TMF has inhibitory effects on various tumor cells. Its mechanisms may involve inducing apoptosis, blocking the cell cycle, and suppressing tumor-related signaling pathways. TMF can regulate the NF-κB and MAPK signaling pathways, inhibiting tumor cell proliferation and migration. Although related research is still in the in vitro stage, its anti-tumor potential deserves further in-depth exploration.
Given TMF's high blood-brain barrier penetration ability, researchers are interested in its potential applications in neurological diseases. TMF can reduce nerve cell damage and protect nerve function through antioxidant and anti-inflammatory mechanisms. Some in vitro and animal model studies have shown that TMF has certain protective effects against ischemic brain injury and neurodegenerative diseases, but the related mechanisms and clinical value still require further validation.
The main mechanism of action of TMF involves regulation of inflammatory mediators and intervention in signaling pathways.
TMF can downregulate iNOS expression, reduce excessive NO production, and alleviate inflammatory responses. iNOS is an inducible enzyme in inflammatory cells; excessive activation leads to massive NO release, leading to tissue damage. TMF exerts anti-inflammatory effects by inhibiting the transcription and translation processes of iNOS, lowering NO levels.
NF-κB is a core transcription factor in inflammatory responses, regulating the expression of various inflammatory factors. TMF can inhibit NF-κB activation, preventing its transfer from the cytoplasm into the nucleus, reducing the expression of inflammatory genes such as TNF-α, IL-1β, and IL-6, thereby alleviating inflammatory responses.
TMF can also regulate the phosphorylation status of members of the mitogen-activated protein kinase (MAPK) family, such as ERK, JNK, and p38, inhibit the transmission of inflammatory signals, and reduce the release of inflammatory mediators.
TMF enhances cellular antioxidant capacity by activating intracellular antioxidant enzyme systems such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), enhancing cellular antioxidant capacity, reducing ROS accumulation, and protecting cells from oxidative damage.
The druggability parameters of TMF indicate that it has promising potential for drug development.
The molecular weight of TMF is 358.3460, meeting the requirements of the Lipinski rule. The LogP value was 2.5174, indicating moderate lipid solubility, which is beneficial for oral absorption and cell membrane penetration. TPSA is 87.36 Ų, suitable for crossing cell membranes and the blood-brain barrier. It has low water solubility (0.0051 mg/mL), which may affect oral bioavailability, but can be improved through modern formulation technologies such as nanocarriers and solid dispersions.
TMF does not inhibit hERG channels, resulting in a lower risk of cardiotoxicity. The Ames test result was 0.6, indicating a low genotoxicity risk and good safety.
Currently, there is limited research on the systemic pharmacokinetics of TMF. Existing studies suggest that it is well absorbed orally and has a high blood-brain barrier penetration ability, possibly acting on the central nervous system. Metabolic pathways in the body may involve the liver's CYP450 enzyme system, but the specific metabolites and clearance mechanisms require further research.
As a natural flavonoid compound, TMF shows broad clinical application prospects due to its remarkable anti-inflammatory, antioxidant, and potential neuroprotective and antitumor activities.
TMF can be used as a candidate molecule for novel anti-inflammatory drugs in the treatment of chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Its low toxicity and multi-target mechanism of action are expected to overcome the side effects of traditional anti-inflammatory drugs.
TMF's ability to penetrate the blood-brain barrier gives it potential value in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as ischemic brain injury. More animal models and preclinical studies are needed in the future to verify its neuroprotective mechanisms and efficacy.
The inhibitory effect of TMF on tumor cells suggests it may serve as an adjunct antitumor drug. Combined with modern drug design and targeted delivery systems, it is expected to enhance antitumor activity and selectivity.
As a flavonoid derived from traditional medicinal plants, hemidentinol-5-methyl ether has become a hot topic in pharmacological research and new drug development due to its remarkable anti-inflammatory activity and good druggability parameters. Its multi-target and multi-mechanism mode of action offers new ideas for treating inflammation and related diseases. In the future, through systematic pharmacokinetics, toxicology studies, and clinical validation, TMF is expected to become a natural drug or drug-leading compound with clinical value. Ongoing and in-depth basic and applied research will drive scientific progress and clinical translation of TMF in the field of natural product pharmacology.
