Product name: Octyl gallate
Synonym name:
Catalogue No.: BP3279
Cas No.: 1034-01-1
Formula: C₁₅H₂₂O₅
Mol Weight: 282.336
Botanical Source:
Physical Description:
Type of Compound: Aliphatics

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.

NMR of Octyl gallate

HPLC of Octyl gallate

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

Introduction/Overview

In the field of natural product chemistry and pharmacology research, gallic acid and its ester derivatives have attracted much attention due to their extensive biological activities. Octyl gallate (OG), also known as Progallin O, with the chemical name 3,4,5-trihydroxybenzoic acid octyl ester, is an important alkyl gallate ester. Its CAS number is 1034-01-1. For a long time, OG has been widely used as an additive (E311) in the food and cosmetics industry worldwide due to its excellent antioxidant and antibacterial properties, to delay oil rancidity and product deterioration. However, recent studies have continuously revealed that the biological functions of OG go far beyond preservation and preservation. A large number of in vitro and in vivo studies have shown that OG exhibits significant activity in antiviral, anti-inflammatory, neuroprotective, and potential anti-tumor aspects, especially its antiviral effects against herpes simplex virus type 1 (HSV-1), vesicular stomatitis virus (VSV), and poliovirus, providing convincing evidence for its transformation from food additives to therapeutic drug molecules. In addition, its unique, selective, and sensitive fluorescence properties also provide the possibility for developing OG based molecular probes and biological imaging tools. This article aims to systematically review the chemical properties, sources, pharmacological activities, molecular mechanisms of action, pharmacological parameters, and clinical application prospects of octyl gallate, in order to provide comprehensive academic references for the in-depth development and utilization of this compound.

Chemical structure and physicochemical properties

The molecular formula of octyl gallate is C15H22O5, with a molecular weight of 282.3360 g/mol. Its chemical structure is composed of a core of gallic acid (3,4,5-trihydroxybenzoic acid) and an eight carbon straight chain alkyl group (octyl) connected by ester bonds. This structure cleverly combines the hydrophilicity of polyphenolic hydroxyl groups with the lipophilicity of long-chain alkyl groups.

The key physicochemical properties are as follows:
1. solubility OG exhibits typical parental characteristics. Three adjacent phenolic hydroxyl groups give it a certain degree of water solubility (about 0.1388 mg/mL), while the long chain of octyl gives it good lipid solubility. Its lipid water partition coefficient (LogP) is 4.4780, indicating that OG is more soluble in organic solvents and lipid environments, which facilitates its penetration into cell membranes.
2. Acidity and stability The three phenolic hydroxyl groups on the benzene ring give it weak acidity and facilitate the formation of intramolecular hydrogen bonds, which is closely related to its antioxidant activity. Under alkaline conditions, ester bonds may undergo hydrolysis, producing gallic acid and octanol.
3. Spectral characteristics One of the most distinctive properties of OG is its fluorescence properties. The conjugated system in its molecular structure enables it to emit fluorescence at specific excitation wavelengths, and this fluorescence signal has selectivity and sensitivity to the polarity, viscosity, and binding with specific biomolecules of the microenvironment, making it potentially applicable in the fields of biosensing and imaging.
4. Topological Polarity Surface Area (TPSA)Its TPSA is 86.99 Å ², which is relatively small. Combined with its moderate LogP value, it suggests that it may have good membrane permeability.

These physicochemical properties are the basis for its subsequent biological activity and pharmacokinetic behavior.

Plant sources and extraction methods

Octadecyl gallate is not a widely present major component in nature, but as a derivative of gallic acid, its natural precursor - gallic acid - is widely present in various plants, such as galls of galls in the Rhus family, tea, oak bark, pomegranate, grape, and various Chinese medicinal herbs (such as rhubarb and elm). At present, commercialization and laboratory acquisition of OG are mainly achieved through the following two channels:

1. Chemical Synthesis This is the most important and economical method for producing OG. Usually, gallic acid and n-octanol are used as raw materials and synthesized through esterification reaction in the presence of acidic catalysts (such as concentrated sulfuric acid, p-toluenesulfonic acid) or dehydrating agents (such as dicyclohexylcarbodiimide, DCC). In recent years, in pursuit of green chemistry, enzymatic catalysis (such as using lipase to catalyze in non-aqueous systems) has also been widely studied. This method has the advantages of mild conditions, high selectivity, and few by-products.
2. Plant Extraction and Separation Despite its low natural content, OG can still be directly isolated from certain plant materials. For example, it has been detected in the metabolites of pomegranate peel, certain lichens, and fungi. The extraction process usually uses organic solvents (such as methanol, ethanol, ethyl acetate) for extraction or ultrasound assisted extraction, followed by separation and purification through techniques such as silica gel column chromatography and preparative high-performance liquid chromatography (HPLC). However, due to its low natural abundance, this method is costly and mainly used for scientific research.

Pharmacological activity research

Numerous studies have confirmed that octyl gallate has diverse pharmacological activities, far exceeding its traditional understanding as an antioxidant.

1. antioxidant activity This is the most classic and core activity of OG. The three adjacent phenolic hydroxyl groups on its benzene ring are potent hydrogen donors that can effectively scavenge free radicals (such as superoxide anions, hydroxyl radicals, and peroxide radicals), interrupt the lipid peroxidation chain reaction, and protect cell membranes and biomolecules (such as DNA and proteins) from oxidative damage. Research has shown that the antioxidant capacity of OG is stronger than its parent gallic acid and some short chain alkyl esters (such as propyl ester and butyl ester), which is attributed to the enhanced dispersion and localization ability of octyl long-chain in the lipid phase, making it easier to approach the sites where lipid peroxidation occurs.

2. Antiviral activity OG exhibits broad-spectrum and significant antiviral potential. Research shows that OG can effectively inhibit Herpes simplex virus type 1 (HSV-1)The replication may occur by interfering with virus adsorption or entering the early stages of host cells. Correct Vesicular stomatitis virus (VSV)and Poliovirus， OG also exhibits strong inhibitory effects, which may be related to the destabilization of the viral envelope or capsid, or interference with the synthesis of viral RNA. These findings suggest that OG may serve as a lead compound for the development of novel antiviral drugs.

3. Antibacterial activity OG has inhibitory effects on various bacteria and fungi, including Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and some yeast. Its antibacterial mechanism may be related to the destruction of microbial cell membrane integrity, inhibition of key enzyme activity, and indirect impact of its antioxidant effect on microbial metabolism.

4. Anti inflammatory and immune regulatory activity In cellular and animal inflammation models, OG has been shown to inhibit the production of pro-inflammatory mediators such as nitric oxide, prostaglandin E2, tumor necrosis factor - α, interleukin-6, etc. This effect is closely related to its regulation of related signaling pathways.

5. Neuroprotective activity Based on its strong antioxidant and anti-inflammatory abilities, OG has shown protective effects in cellular and animal models of neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. It can alleviate neuronal damage caused by oxidative stress and inflammatory reactions, and improve cognitive and motor function deficits.

6. Other potential activities Preliminary studies also suggest that OG may have activities such as inhibiting the proliferation of certain tumor cells, protecting the liver from chemical damage, and regulating glucose and lipid metabolism, but further research is needed in these areas.

Mechanism of action and molecular targets

The multiple pharmacological activities of OG stem from its interactions with various biomolecules and signaling pathways. Its core mechanism revolves around anti-oxidative stress Expand and extend to multiple levels such as anti-inflammatory and antiviral.

1. Direct antioxidant and enzyme regulation：

   • Directly eliminate free radicals The phenolic hydroxyl group of OG can directly neutralize reactive oxygen/nitrogen species.
   • Activate Nrf2/ARE pathway This is the key mechanism by which OG exerts cellular protective effects. OG can promote Nuclear factor E2 related factor 2 (NRF2, encoded by NFE2L2 gene) Dissect from the cytoplasm and translocate to the nucleus. In the nucleus, NRF2 binds to antioxidant response elements (ARE), initiating the transcription of a series of phase II detoxifying enzymes and antioxidant proteins, including:
     • Heme oxygenase-1 (HMOX1)
     • Superoxide dismutase (SOD1, SOD2)
     • Catalase (CAT)
     • Glutathione peroxidase 1 (GPX1)
       The activation of this pathway systematically enhances the antioxidant defense ability of cells.

2. Anti inflammatory mechanism：

   • OG can inhibit the activation of pro-inflammatory signaling pathways such as nuclear factor kappa B (NF - κ B), thereby downregulating the expression of inflammatory factors.
   • The study also found that OG can inhibit Matrix metalloproteinases (such as MMP1, MMP3) Expression and activity. MMPs play a crucial role in inflammation, tissue remodeling, and tumor metastasis, and their inhibition helps alleviate tissue damage.

3. Antiviral mechanism：

   • For enveloped viruses such as HSV-1, the lipophilic octyl chain of OG may insert into the viral envelope, disrupting its integrity and preventing the fusion of the virus with the host cell membrane.
   • Inhibition may also be achieved by interfering with certain key enzymes in the virus replication cycle, such as proteases and polymerases, with specific targets still under investigation.

4. Inhibition of Tyrosinase (TYR)：

   • OG is an effective inhibitor of tyrosinase. Tyrosinase is the rate limiting enzyme in melanin biosynthesis and is also involved in the formation of neuromelanin in certain neurological diseases, such as Parkinson's disease. Therefore, the TYR inhibitory activity of OG is related to its potential applications in skin whitening products and neuroprotection.

Evaluation of drug properties and pharmacokinetics

Based on the provided pharmacological parameters and existing research, the preliminary evaluation of the pharmacological properties of OG is as follows:

• Molecular weight (282.34)Less than 500, meeting the requirements of Lipinski's "Five Rules" for oral drug molecules.
• Lipid water partition coefficient (LogP=4.48)This value is slightly higher than the ideal range (usually considered 2-3 to be better), indicating strong lipid solubility of OG. This is beneficial for its penetration through the cell membrane, but may result in poor water solubility (measured at 0.1388 mg/mL), affecting its dissolution and distribution in body fluids. This is one of the key parameters that need to be optimized for its development as a drug.
• Topological Polarity Surface Area (TPSA=86.99 Å ²)Less than 140 Å ² indicates good membrane permeability.
• Preliminary Safety Assessment：
  • HERG inhibition The data shows' no ', which is a positive signal indicating that OG may not inhibit the hERG potassium channel in the heart at conventional concentrations, reducing the risk of causing QT interval prolongation and arrhythmia.
  • Ames test (0.0)The Ames test results are usually expressed in terms of whether they induce mutations. The "0.0" data may indicate that no mutagenicity was observed under the test conditions, but it needs to be interpreted in conjunction with specific experimental reports. This provides preliminary favorable evidence for its genetic toxicity risk.
• Blood-brain barrier (BBB) permeability Predicted as' low '. Although its high LogP value is beneficial for BBB penetration, its TPSA value and polar groups in the molecule may limit its free diffusion. For the treatment of central nervous system diseases, structural modifications or delivery systems may be required to enhance their ability to enter the brain.

Pharmacokinetic study Relatively limited. Based on its ester bond structure, OG is likely to be rapidly hydrolyzed by esterases in vivo, producing gallic acid and octanol. Gallic acid can be absorbed and further metabolized into methylated or sulfated/glucuronic acid complexes, which are excreted through urine. Octanol can be oxidized and metabolized. Therefore, the oral bioavailability of OG may not be high, and its pharmacological effects may be partially attributed to its metabolite gallic acid. Future research needs to clarify the absorption, distribution, metabolism, and excretion (ADME) process of the prototype drug of OG in vivo.

Clinical application prospects and prospects

From a mature food additive to a therapeutic drug, octyl gallate has unique advantages and challenges.

Application Prospects：
1. Localized antiviral/antibacterial agents In view of its good skin permeability and anti HSV-1 activity, OG is expected to be developed into cream, gel and other topical preparations for the treatment of herpes labialis and genital herpes. Its antibacterial properties can also be used to treat skin bacterial or fungal infections.
2. Adjuvant therapy for inflammation related diseases As an antioxidant and anti-inflammatory agent, OG may be used as a dietary supplement or adjuvant medication for the adjuvant management of chronic inflammatory diseases such as arthritis and colitis.
3. Preventive agents for neurodegenerative diseases Its neuroprotective activity makes it potential for preventing or delaying the progression of Parkinson's disease and Alzheimer's disease, which may be applied in the form of functional foods or health products.
4. Functional cosmetic ingredients Combining its antioxidant, anti-inflammatory, and tyrosinase inhibitory activities, OG has been applied in anti-aging, whitening, and sun protection skincare products. In the future, its efficacy monitoring products based on fluorescence characteristics can be further developed.
5. Chemical preventive agent Continuous low-dose intake in food and health products may reduce the risk of oxidative stress-related diseases (such as cancer and cardiovascular disease) through their antioxidant mechanisms.
6. Biological probes and imaging agents Its selective fluorescence properties need to be further explored, or molecular probes can be developed for detecting specific redox states or metal ions within cells.

Challenges and Prospects：
1. Bioaccumulation and Formulation Optimization Improving oral bioavailability is key. The strategy includes developing prodrugs (such as preparing more easily hydrolyzed esters), using nanocarrier systems (liposomes, nanoemulsions, polymer nanoparticles) to package and improve solubility, stability, and targeting.
2. Deep analysis of the mechanism of action In particular, the specific molecular targets of its antiviral and potential anti-tumor effects need to be clarified to guide rational drug design.
3. System security evaluation Although it has a good safety record as a food additive, as a long-term medication, comprehensive preclinical toxicology studies (acute toxicity, long-term toxicity, reproductive toxicity, etc.) and standardized clinical trials are required.
4. Structural modification and development of analogues Using OG as the lead compound, by modifying the alkyl chain length and introducing other functional groups, it is expected to obtain new derivatives with stronger activity, higher selectivity, and better pharmacokinetic properties.

Conclusion

Octyl gallate is a bridging molecule that connects the food industry and the pharmaceutical industry. It is not only an efficient antioxidant preservative, but also a treasure compound with multiple pharmacological activities. From clearing free radicals to regulating the Nrf2 core defense pathway, from inhibiting herpes virus to protecting neurons, OG exhibits its versatile characteristics. Although there are still challenges in terms of bioavailability, target accuracy, and system safety on the road to mature therapeutic drugs, its clear mechanism of action, good safety substrate, and unique physicochemical properties (such as fluorescence characteristics) have laid a solid foundation for its deep development in multiple directions such as therapeutic drugs, functional products, and biological tools. Future research should focus on using modern pharmaceutical technologies to improve its delivery efficiency, and using chemical biology methods to further elucidate its interactions with disease-related targets, in order to fully unleash the therapeutic potential of this natural derivative and benefit human health.