Product name: Diosmetin
Synonym name: 3',5,7-Trihydroxy-4'-methoxyflavone; Luteolin 4′-methyl ether; Salinigricoflavonol; Vitamin P
Catalogue No.: BP0506
Cas No.: 520-34-3
Formula: C₁₆H₁₂O₆
Mol Weight: 300.266
Botanical Source: Citrus limon (L.) Burm. f.
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.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

HPLC of Diosmetin

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

Introduction/Overview

Natural products have long been an important source of innovative drug discovery, with flavonoid compounds receiving much attention due to their broad biological activity and low toxicity. Diosmetin, also known as 5,7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -4H-phenylpyran-4-one, is an important monomethoxyflavonoid. As a 4 '- methyl ether derivative of luteolin, it is widely present in citrus fruits and various medicinal plants. Early research mainly focused on its antioxidant properties, but with the development of molecular pharmacology, the pharmacological activities of lignin in various aspects such as anti-tumor, anti-inflammatory, cardiovascular protection, and neuroprotection have gradually been revealed. Especially as an effective inhibitor of human cytochrome P450 1A (CYP1A) enzyme (IC50 of 40 μ M in HepG2 cells), it suggests its potential value in chemoprevention and drug interactions. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, and medicinal properties of lignin from fragrant leaves, and to explore its clinical application prospects as a candidate drug or functional ingredient.

Chemical structure and physicochemical properties

The molecular formula of lignin in fragrant leaves is C16H12O6, with a molecular weight of 300.2660. Its core structure is the flavonoid nucleus, characterized by the presence of two phenolic hydroxyl groups at positions 5 and 7 of the A ring, a hydroxyl group at position 3 'of the B ring, and a methoxy group at position 4'. This specific substitution pattern of hydroxyl and methoxy groups is the key structural basis for its biological activity, affecting its electron distribution, hydrogen bonding ability, and interaction with biomolecules.

In terms of physical and chemical properties, lignin exhibits typical flavonoid characteristics. The calculated lipid water partition coefficient (LogP) is 2.2286, indicating that it has moderate lipophilicity and is conducive to transmembrane transport. The topological polar surface area (TPSA) is 100.1300 Å ², reflecting the area occupied by polar functional groups (such as hydroxyl and carbonyl) in the molecule. Its water solubility is relatively low, about 0.0397 mg/mL, which to some extent limits its bioavailability. Fragrant leaf lignin is a light yellow crystalline powder at room temperature, with characteristic absorption peaks at around 250 nm and 350 nm in its UV absorption spectrum, which can be used for qualitative and quantitative analysis. The presence of catechol (ring A) and meta phenyltriphenylphenol (ring B) in its structure endows it with strong metal chelating ability and potential for free radical scavenging.

Plant sources and extraction methods

Fragrant lignin is widely distributed in nature and mainly comes from citrus plants in the Rutaceae family, such as lemon, lime, and citrus peel and leaves. In addition, there are also high levels in leguminous plants such as catnip, lip shaped plant rosemary, and olive leaves. In these plants, vanillin often exists in the form of free glycosides or its glycosides (such as Diosmin).

Organic solvent extraction is commonly used to extract lignin from plant materials. Polar solvents such as methanol, ethanol, and acetone are commonly used due to their good solubility in flavonoids. In order to improve extraction efficiency and selectivity, 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 enrich lignin from citrus peels. After extraction, further separation and purification steps are usually required, such as macroporous resin adsorption, silica gel column chromatography, preparative high-performance liquid chromatography, etc., to obtain high-purity lignin monomers. Its glycoside form, naringin, can be hydrolyzed and converted into naringin by gut microbiota in vivo, which is also one of the important pathways for its pharmacological effects.

Pharmacological activity research

Numerous in vitro and in vivo studies have confirmed that lignin from fragrant leaves has diverse pharmacological activities, making it a potential candidate molecule for multi-target therapy.

1. Antitumor activity: geranium lignin has growth inhibition and apoptosis promoting effects on a variety of cancer cell lines, including liver cancer, breast cancer, colon cancer, lung cancer and prostate cancer. Its function is not limited to inducing cell apoptosis, but also includes inhibiting cell proliferation, migration, invasion, and angiogenesis.
2. Antioxidant and anti-inflammatory activities Fragrant leaf lignin can effectively eliminate free radicals such as DPPH and ABTS, and enhance the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase in cells. In the lipopolysaccharide induced macrophage inflammation model, it can significantly inhibit the production of pro-inflammatory factors such as nitric oxide, prostaglandin E2, tumor necrosis factor alpha, and interleukin-6.
3. Cardiovascular protective activity Research has shown that lignin in fragrant leaves has vasodilatory effects, which may be achieved through endothelial dependent and non dependent pathways. In animal models, it has shown the role of reducing myocardial ischemia reperfusion injury, inhibiting atherosclerotic plaque formation and improving cardiac function.
4. Neuroprotective and Osteoprotective Activities Fragrant leaf lignin has been identified as an agonist of the tropomyosin related kinase B receptor, suggesting its potential for neural nutrition and neuroprotection, and may play a role in neurodegenerative diseases. In addition, it can maintain bone density in experimental osteoporosis models by regulating the activity of osteoblasts and osteoclasts.
5. Other activities Fragrant leaf lignin also has a wide range of biological activities such as antibacterial, antiviral, and hepatoprotective properties.

Mechanism of action and molecular targets

The various pharmacological activities of lignin in fragrant leaves stem from its regulation of multiple signaling pathways within cells and its interactions with multiple key target proteins.

In Mechanism of anti-tumor action In terms of function, the action of lignin in fragrant leaves is multi-target:
* Inducing cell apoptosis By downregulating the expression of anti apoptotic proteins B cell lymphoma 2 (BCL2) and myeloid leukemia 1 (MCL1), while upregulating pro apoptotic proteins, the mitochondrial apoptosis pathway is activated.
* Inhibit survival signals It can effectively inhibit the phosphorylation and activation of signal transduction and transcription activator 3 (STAT3), and block the transcription of downstream genes that promote survival and proliferation.
* Inhibit invasion and metastasis Downregulate the expression and activity of matrix metalloproteinase-2 (MMP2), thereby inhibiting the degradation and invasion of extracellular matrix by cancer cells.
* Interference with DNA metabolism and hypoxia response By inhibiting the activity of topoisomerase I (TOP1) and topoisomerase II alpha (TOP2A), it interferes with DNA replication and repair. At the same time, inhibiting the stability and transcriptional activity of hypoxia inducible factor-1 alpha (HIF1A) disrupts tumor hypoxia adaptation and angiogenesis.
* Regulating kinases and hormone pathways Inhibiting the activity of mitogen activated protein kinase 1 (MAPK1/ERK2) and affecting cell proliferation signaling. In addition, its regulatory effect on estrogen receptor alpha (ESR1) and aromatase (CYP19A1) may play an important role in the treatment of hormone dependent tumors (such as breast cancer).

its Anti inflammatory and antioxidant mechanisms Involved in inhibiting the activation of inflammation related transcription factors such as nuclear factor kappa B (NF - κ B) and activator protein-1 (AP-1), while activating the Nrf2/ARE antioxidant defense pathway.

Cardiovascular protection mechanism Related to promoting nitric oxide synthesis, inhibiting abnormal proliferation of vascular smooth muscle cells, and their inherent antioxidant stress resistance. But Neuroprotective effect It is mainly related to the activation of TrkB receptors, which in turn activate downstream survival pathways such as PI3K/Akt and MAPK/ERK.

Evaluation of drug properties and pharmacokinetics

Although the pharmacological activity of lignin in fragrant leaves is significant, its medicinal properties still need to be comprehensively evaluated.

• Absorption, distribution, metabolism, excretion The rapid but incomplete absorption of lignin after oral administration, as well as its low water solubility and first pass effect, are the main factors limiting its oral bioavailability. In the body, lignin undergoes extensive II binding metabolism, such as glucuronidation and sulfation. The prototype drug and metabolites are mainly excreted through urine and bile. It is worth noting that lignin from fragrant leaves has strong inhibitory activity against CYP1A enzyme (IC50 40 μ M), which suggests that it may interact with drugs metabolized by this enzyme and should be taken into consideration when used in combination therapy.
• Preliminary evaluation of safety According to the provided pharmacological parameters, vanillin has no significant inhibitory effect on hERG potassium channels, indicating a low risk of causing QT interval prolongation in the heart. The Ames test result is 0.6 (usually considered negative if the ratio is less than 2), indicating that it has no significant genetic toxicity. Its blood-brain barrier permeability is predicted to be "low", which is an unfavorable factor for the treatment of central nervous system diseases, but may also reduce its potential side effects on the central nervous system.
• Formulation and delivery strategy challenges In order to improve its bioavailability, researchers are exploring various strategies, including preparing its prodrug (such as quercetin), developing nano formulations (liposomes, nanoparticles, solid dispersions), and using techniques such as cyclodextrin inclusion. These technologies aim to increase their solubility, stability, and targeting.

Clinical application prospects and prospects

Fragrant leaf lignin exhibits broad potential for conversion from dietary supplements to therapeutic drugs.

1. As a functional food and dietary supplement Its rich natural sources and good safety profile make it very suitable for development as a functional food or health product for preventing chronic diseases such as cancer and cardiovascular disease.
2. As a chemical preventive agent Due to its antioxidant, anti-inflammatory, and carcinogenic activating enzyme (CYP1A) inhibiting properties, lignin can be used for chemoprevention in high-risk populations, such as reducing DNA damage caused by environmental carcinogens.
3. As an adjuvant therapy drug In the field of cancer treatment, the combination of lignin and conventional chemotherapy drugs (such as topoisomerase inhibitors) may produce synergistic effects, reduce chemotherapy dosage and toxic side effects, and reverse multidrug resistance. Its therapeutic value in cardiovascular disease, osteoporosis, and neurodegenerative diseases also deserves further exploration.
4. Future research directions：
   • structural optimization Improving its water solubility and metabolic stability through chemical modification, enhancing its bioavailability and targeting.
   • Deepening mechanism Using proteomics, metabolomics, and gene editing technologies to more accurately elucidate its multi-target action network and dominant mechanism.
   • Preclinical and clinical research It is necessary to conduct systematic long-term animal toxicity tests and design rigorous clinical trials to verify its effectiveness and safety in humans.
   • New delivery system Actively developing targeted delivery systems based on nanotechnology to improve their therapeutic efficacy.

Conclusion

Xiangye lignin, as a natural source of monomethoxyflavonoids, has become a star molecule in natural product pharmacology research due to its multifaceted pharmacological activities and multi-target mechanisms of action. From inhibiting CYP1A enzyme to regulating multiple key targets such as STAT3, BCL2, TrkB, its biological effects cover multiple major disease fields such as cancer, inflammation, cardiovascular and neurological diseases. Despite facing challenges such as low bioavailability in drug development, these obstacles are expected to be overcome through the modification and optimization of modern medicinal chemistry and pharmacology methods. In the future, with the continuous deepening of basic research and the continuous promotion of translational applications, lignin and its derivatives are expected to move from the laboratory to clinical practice, providing important lead compounds and scientific basis for the development of new, efficient, and low toxicity multi-target therapeutic drugs.