Product name: Methyl gallate
Synonym name:
Catalogue No.: BP3412
Cas No.: 99-24-1
Formula: C₈H₈O₅
Mol Weight: 184.147
Botanical Source:
Physical Description:
Type of Compound: Phenols

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.

HPLC of Methyl gallate

NMR of Methyl gallate

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

Introduction/Overview

Natural products have always been an important treasure trove for innovative drug discovery, among which plant phenolic compounds have attracted much attention due to their wide range of biological activities. Methyl gallate (MG), also known as 3,4,5-trihydroxybenzoic acid methyl ester, is a simple phenolic acid ester compound widely present in various medicinal plants. Its CAS number is 99-24-1 and it is a methylated derivative of gallic acid. Early research mainly focused on its role as a natural antioxidant, but with the deepening of modern pharmacological research, the pharmacological activities of MG in various aspects such as anti-cancer, anti-inflammatory, antibacterial, and even antiviral (such as anti-HIV-1) have gradually been revealed, showing great potential as a lead compound or therapeutic agent. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of methyl gallate, in order to provide comprehensive academic references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of methyl gallate is C8H8O5, with a molecular weight of 184.1470 g/mol. Its chemical structure consists of a methyl benzoate skeleton, with three hydroxyl groups replacing the 3, 4, and 5 positions of the benzene ring. This adjacent triphenylhydroxyl structure is the key pharmacophore for its strong antioxidant activity. This structure enables it to serve as both a hydrogen donor and a stable free radical through single electron transfer, which is the chemical basis for its many biological activities.

In terms of physicochemical properties, the lipid water partition coefficient (LogP) of MG is 1.2261, indicating that it has a certain degree of lipophilicity, but overall it still leans towards hydrophilicity. Its topological polar surface area (TPSA) is 86.99 Å ², reflecting the proportion of polar hydroxyl groups in its molecule. The water solubility data is 7.1270 (usually referring to logS or related solubility parameters, the specific unit depends on the model), indicating that it has a medium to high solubility in water, which is beneficial for its absorption and distribution in organisms. These basic physicochemical parameters provide a basis for its subsequent pharmacokinetic and pharmacological analysis.

Plant sources and extraction methods

Methyl gallate is widely distributed in nature and is a secondary metabolite of many plants. It is commonly found in the following families and genera of plants: Euphorbiaceae (such as Eucommia ulmoides and Phyllanthus urinae), Sapindaceae (such as mangoes and cashews), Rosaceae (such as roses and raspberries), Rosaceae (such as walnuts), and Theaceae (such as tea leaves). In these plants, MG often coexists with other polyphenolic compounds such as gallic acid and tannic acid.

The extraction of MG from plant materials mainly depends on its polarity and solubility. The conventional extraction methods include:
1. Solvent extraction method The most commonly used method is to use methanol, ethanol, acetone, or water alcohol mixed solvents for extraction, reflux, or ultrasound assisted extraction. Methanol and ethanol are commonly used due to their high extraction efficiency for phenolic substances.
2. Advanced Extraction Technology To improve extraction efficiency and selectivity, technologies such as microwave-assisted extraction (MAE), supercritical fluid extraction (SFE, commonly CO2 entraining modifier), and pressurized liquid extraction (PLE) have also been applied.
The crude extract after extraction usually requires further separation and purification steps, such as liquid-liquid extraction (enrichment with organic phases such as ethyl acetate), column chromatography (silica gel, Sephadex LH-20, macroporous adsorption resin, etc.), and high performance liquid chromatography (HPLC) preparation, to obtain high-purity MG monomers.

Pharmacological activity research

Numerous in vitro and in vivo studies have confirmed that methyl gallate has diverse and significant pharmacological activities.

1. antioxidant activity One of the core activities of MG. Its adjacent triphenylhydroxyl structure can effectively scavenge various free radicals such as DPPH, ABTS, superoxide anions, hydroxyl radicals, etc., and exhibits strong iron ion reduction ability. In cellular and animal models, it can significantly reduce oxidative stress markers such as ROS and MDA, and enhance the activity of endogenous antioxidant enzyme systems.

2. anti-inflammatory activity Research has shown that MG can effectively inhibit the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by macrophages (such as RAW 264.7) induced by stimuli such as lipopolysaccharide (LPS), and downregulate the expression of pro-inflammatory cytokines (such as TNF - α, IL-1 β, IL-6). It has shown good anti-inflammatory effects in animal inflammation models, such as carrageenan induced foot swelling and acetic acid induced increased vascular permeability in mice.

3. anticancer activity: MG has growth inhibition and apoptosis induction effects on a variety of human cancer cell lines, including breast cancer (MCF-7), lung cancer (A549), liver cancer (HepG2), prostate cancer (PC-3), colon cancer (HT-29), etc. Its function is not limited to inducing cell apoptosis, but also involves inhibiting cell proliferation, migration, invasion, and cell cycle arrest.

4. Antibacterial and antiviral activity MG has inhibitory effects on various Gram positive bacteria (such as Staphylococcus aureus) and Gram negative bacteria (such as Escherichia coli), and its mechanism may be related to the destruction of bacterial cell membrane integrity, inhibition of biofilm formation, or interference with bacterial enzyme systems. Of particular note is its antiviral potential, as studies have reported that MG can inhibit the activity of HIV-1 reverse transcriptase and integrase, thereby interfering with the replication cycle of HIV-1 virus.

5. Other activities In addition, the study also suggests that MG may have potential activities such as liver protection, neuroprotection, and anti diabetes complications, which are closely related to its core role of antioxidant and anti-inflammatory.

Mechanism of action and molecular targets

The multiple pharmacological activities of methyl gallate stem from its diverse regulation of cellular signaling pathways and its effects on specific molecular targets.

• Antioxidant and cellular defense pathways The antioxidant effect of MG is not only achieved through direct clearance of free radicals, but more importantly, through activation Nuclear factor E2 related factor 2 (NRF2, encoded by NFE2L2 gene) Signal pathway. MG can promote the dissociation and translocation of NRF2 from the cytoplasm to the nucleus, where it binds to antioxidant response elements, thereby upregulating the expression of a series of phase II detoxifying enzymes and antioxidant proteins, including Heme oxygenase-1 (HMOX1)、Superoxide dismutase (SOD1, SOD2)、Catalase (CAT) and Glutathione peroxidase 1 (GPX1) Wait, the system enhances the antioxidant defense ability of cells.

• Anti inflammatory and anti-cancer related pathways：

  • NF - κ B pathway MG can inhibit the degradation of I κ B α, prevent the nuclear translocation of NF - κ B p65 subunit, and thus downregulate the expression of downstream pro-inflammatory factors and pro survival genes.
  • MAPK pathway Research has shown that MG can regulate the phosphorylation levels of proteins such as ERK, JNK, and p38 MAPK, affecting cell proliferation, apoptosis, and inflammatory response.
  • Matrix metalloproteinases (MMPs)MG can inhibit MMP-1 (interstitial collagenase) and MMP-3 (matrix metalloproteinase-1) One of the key mechanisms by which it inhibits tumor cell invasion and metastasis is its expression and activity.
  • Tyrosinase (TYR)MG has an inhibitory effect on TYR, which is related to its antioxidant properties and may also play a role in regulating melanin production.
  • Apoptotic pathway MG can regulate the Bcl-2/Bax ratio, activate Caspase cascade reactions (such as Caspase-3, -9), and induce cell apoptosis through the mitochondrial pathway.

• Direct enzyme inhibition As mentioned earlier, MG can directly inhibit HIV-1 reverse transcriptase and integrase, as well as certain key enzymes required for bacterial growth, which are its direct targets for antiviral and antibacterial effects.

Evaluation of drug properties and pharmacokinetics

Based on its physicochemical properties and preliminary biological data, a preliminary evaluation of the pharmacological properties of methyl gallate is conducted

• Preliminary assessment of drug properties MG has a small molecular weight (<500), moderate LogP, and acceptable TPSA, meeting multiple criteria in Lipinski's "Five Rules" and possessing the basic chemical space to become an oral medication.
• Preliminary safety indicators：
  • HERG inhibition The data shows' no ', indicating a low risk of potential cardiac toxicity (causing QT interval prolongation), which is a favorable safety feature.
  • Genotoxicity (Ames test)The data is 0.6 (usually referring to the recovery mutation rate, the specific meaning needs to be determined based on the experimental system, but a lower value usually indicates a lower risk of mutagenicity), which preliminarily indicates that it has no obvious genetic toxicity.
  • Blood-brain barrier (BBB) permeability Predicted as' low ', it means that it may not easily enter the central nervous system, which can reduce central side effects for treating peripheral diseases, but is a disadvantageous factor for treating central nervous system diseases.
• Pharmacokinetic Challenge Despite their simple structure, phenolic compounds often face issues of rapid metabolism and elimination in the body. MG may undergo extensive II binding reactions (such as glucuronidation and sulfation) in the body, resulting in low oral bioavailability. In addition, its catechol structure may undergo oxidation under physiological conditions, affecting its stability. Therefore, future research needs to focus on its pharmacokinetic characteristics in vivo, including absorption, distribution, metabolism, and excretion processes, and may improve its pharmacokinetic properties through structural modifications such as prodrugs or analogues.

Clinical application prospects and prospects

Methyl gallate, as a natural small molecule with multiple targets and functions, has broad clinical application prospects but also faces challenges.

1. Potential application directions：

   • Auxiliary antioxidant/anti-inflammatory therapeutic agents Can be used as a functional food additive or health supplement ingredient for the prevention or adjuvant treatment of diseases related to oxidative stress and chronic inflammation, such as metabolic syndrome, early intervention of neurodegenerative diseases, etc.
   • Anticancer adjuvant therapy or chemopreventive agents Given its inhibitory effect on various cancer cells and relatively low toxicity to normal cells, it can be explored as an adjuvant chemotherapy drug to reduce side effects, or as a chemopreventive agent for high-risk populations.
   • Local medication: Use its antibacterial and anti-inflammatory properties to develop topical agents (such as cream and gel) for treating skin infections, acne or promoting wound healing.
   • Antiviral lead compound Its anti-HIV-1 activity provides valuable lead structures for the development of novel antiretroviral drugs.

2. Challenges and Prospects Faced：

   • Activity optimization and selectivity Through systematic structure-activity relationship research, its structure needs to be modified to enhance specific pharmacological activity (such as anti-cancer) while improving target selectivity and reducing off target effects.
   • Enhancement of medicinal properties Focus on addressing its potential low oral bioavailability and rapid metabolism issues. Nano drug delivery systems, such as liposomes and polymer nanoparticles, may be effective strategies for improving their stability, targeting, and bioavailability.
   • In depth mechanism research Although multiple targets have been identified, their core functional nodes in multi-path networks and the primary secondary relationships between different activities still need to be more accurately elucidated using omics techniques (proteomics, metabolomics) and gene editing tools.
   • Preclinical and clinical research At present, most research is still at the cellular and animal level, and there is an urgent need to conduct standardized preclinical safety evaluations (GLP toxicology) and subsequent clinical trials to verify its effectiveness and safety.

Conclusion

Methyl gallate, as a natural phenolic compound with simple structure but rich biological activity, has shown remarkable potential in various fields such as antioxidant, anti-inflammatory, anticancer, antibacterial and antiviral. Its mechanism of action involves the regulation of key signaling pathways such as NRF2, NF - κ B, MAPK, as well as the inhibition of specific targets such as MMPs and HIV-1 enzymes, reflecting the characteristics of multi-target action. Despite issues such as low blood-brain barrier permeability and potential metabolic challenges in drug development, its good preliminary safety indicators (low hERG inhibition, negative Ames test) have laid the foundation for further development. Future research should focus on improving its pharmacokinetic properties through medicinal chemistry and pharmacology, and conducting systematic preclinical and clinical studies. Methyl gallate is not only a promising candidate molecule in itself, but also an important lead compound, providing valuable structural and mechanistic insights for the development of novel drugs for the treatment of various human diseases.