Propyl gallate's primary mechanism of action is its antioxidant activity, involving free radical scavenging and metal ion chelation. It protects biological systems from oxidative damage by hydrogen peroxide and oxygen free radicals through a catalytic mechanism similar to superoxide dismutase. The compound also modulates heme oxygenase-1 (HO-1) activity and decreases lung cancer cell survival. It induces apoptosis in human leukemia cells and HeLa cells by increasing reactive oxygen species (ROS) levels and depleting glutathione (GSH). Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation.

In vitro, Propyl gallate demonstrates potent antioxidant activity by scavenging free radicals and chelating metal ions. It modulates heme oxygenase-1 (HO-1) activation and decreases lung cancer cell survival. The compound induces apoptosis in human leukemia cells and HeLa cells by increasing ROS levels and depleting GSH. It sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting HO-1 for TRC8-mediated degradation. Propyl gallate also inhibits the production of acrolein, glyoxal, and methylglyoxal, which are toxic carbonyl compounds formed during lipid peroxidation.

In vivo, Propyl gallate has been shown to possess anti-inflammatory, antitumor, and cardioprotective activities. It has been studied for its potential to protect against oxidative stress-related diseases. The compound's antioxidant properties contribute to its cardioprotective effects by reducing oxidative damage to cardiac tissues. Its anti-inflammatory activity is mediated through the modulation of inflammatory pathways. Propyl gallate has also been investigated for its potential chemopreventive effects in various cancer models.

The in vitro antioxidant activity of Propyl gallate is assessed using various free radical scavenging assays. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay involves mixing the compound with a DPPH solution and measuring the decrease in absorbance at 517 nm. The ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical cation decolorization assay measures the ability of the compound to scavenge the ABTS radical cation. The ferric reducing antioxidant power (FRAP) assay measures the compound's ability to reduce ferric ions to ferrous ions. For metal chelation studies, the compound is incubated with ferrous ions and Ferrozine, and the decrease in absorbance is measured.

For cellular assays, various cancer cell lines (e.g., HeLa, leukemia cells, lung cancer cells) are used. Cells are cultured in appropriate media and treated with various concentrations of Propyl gallate (typically 10-200 µM) for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by measuring caspase-3/7 activity, by flow cytometry using Annexin V/PI staining, or by Western blotting for cleaved caspases and PARP. ROS levels are measured using DCFH-DA fluorescence. GSH levels are measured using a colorimetric assay. The expression of HO-1 and other stress-response proteins is analyzed by Western blotting or qPCR.

In vivo studies with Propyl gallate are conducted in various animal models of disease. For cardioprotection studies, rodents are administered Propyl gallate (typically 10-100 mg/kg) orally or intraperitoneally, and cardiac function is assessed by echocardiography or by measuring markers of oxidative stress and inflammation in cardiac tissues. For antitumor studies, mice bearing tumor xenografts are treated with Propyl gallate (typically 50-200 mg/kg) daily, and tumor growth is monitored. For anti-inflammatory studies, animals are treated with Propyl gallate before or after the induction of inflammation, and inflammatory markers in serum and tissues are measured.

Absorption, Distribution and Excretion
Following oral administration to rats and rabbits, propyl gallate is rapidly metabolized and excreted. …In rats, most propyl gallate is excreted in feces as the orthoester. The orthoester and gallic acid were detected in urine and were completely excreted within 24 hours. In rabbits, 79% of the administered dose was excreted in urine, of which 72% was excreted as 4-methoxygallic acid glucuronide and 6.7% as unconjugated phenolic compounds. Minor metabolites include pyrophenols (free and conjugated) and free 4-methoxygallic acid. In rats, the orally administered propyl gallate is partially absorbed in the gastrointestinal tract. In vivo, the gallate ester is hydrolyzed to gallic acid and free alcohol. The free alcohol is metabolized via the Krebs cycle, and most of the gallic acid is converted to 4-O-methylgallic acid. Free gallic acid or its conjugated derivatives are excreted in urine. Large amounts of unmetabolized esters are excreted in rat feces.
Metabolism/Metabolites
Following oral administration to rats and rabbits, propyl gallate is rapidly metabolized and excreted. …After feeding to rats, most propyl gallate is excreted in feces as the orthoester. The orthoester and gallic acid are detected in urine and are completely excreted within 24 hours. In rabbits, after oral administration of gallate propionate, 79% of the administered dose is excreted in urine, of which 72% is excreted as 4-methoxygallate glucuronide and 6.7% as unconjugated phenolic compounds. Minor metabolites include pyrogallol (free and conjugated) and free 4-methoxygallate.
After oral administration of gallate propionate to rats, a portion of the dose is absorbed in the gastrointestinal tract. In vivo, gallate is hydrolyzed to gallic acid and free alcohol. The free alcohol is metabolized via the Klinefelter cycle, and most of the gallic acid is converted to 4-O-methylgallate. Free gallic acid or its conjugated derivatives (4-O-methylgallic acid) are excreted in the urine. Large amounts of unmetabolized esters are excreted in rat feces. Pig metabolism is similar to that of rats. Current evidence suggests that gallic esters are hydrolyzed to gallic acid in vivo. Most gallic acid is converted to 4-O-methylgallic acid. Free gallic acid or its conjugated derivatives (4-O-methylgallic acid) are excreted in the urine. 4-O-methylgallic acid has been shown to bind with glucuronic acid… In vitro incubation experiments were conducted using homogenates of liver, small intestinal mucosa, and cecal/colonic contents as sources of gut microbiota for propyl gallate, octyl gallate, and dodecyl gallate. The homogenates were incubated with the corresponding gallic esters at 37°C. Samples were taken at different time points over a period of up to 24 hours and analyzed by high-performance liquid chromatography (HPLC). All test substances were extensively metabolized by the intestinal mucosal homogenates. Furthermore, the contents of the cecum and colon also exhibited high metabolic capacity, particularly for propyl gallate. The amount of gallic acid detected during incubation was consistently much smaller than the total reduction in esters. This indicates that, in addition to ester bond hydrolysis, other biotransformation pathways are also crucial for the metabolism of these three gallic esters.
Propyl gallate is a small, lipophilic molecule with good oral bioavailability. It is rapidly absorbed after oral administration and distributed to various tissues. The compound is metabolized in the liver and excreted in urine. Its half-life is relatively short, typically a few hours. The compound is soluble in ethanol and lipids but has limited water solubility. It is stable under normal storage conditions but may degrade when exposed to light, heat, or alkaline conditions.

Propyl gallate is generally recognized as safe (GRAS) for use as a food additive at concentrations up to 0.02% of the fat content. However, some studies have raised concerns about its potential toxicity at high doses. The compound has been shown to cause skin and eye irritation and may be a sensitizer. In animal studies, high doses have been associated with liver and kidney effects. The compound is also known to cause contact dermatitis in sensitive individuals. Its use as a food additive is regulated in many countries, and maximum permitted levels are established for various food products.

[1]. Dual effects of propyl gallate and its methylglyoxal adduct on carbonyl stress and oxidative stress. Food Chem. 2018 Nov 1;265:227-232.

[2]. Scavenging of Acrolein by Food-Grade Antioxidant Propyl Gallate in a Model Reaction System and Cakes. J Agric Food Chem. 2019 Aug 7;67(31):8520-8526.

Propyl gallate is a white to off-white fine crystalline powder, odorless or slightly odorous, with a melting point of 150°C, insoluble in water, and a slightly bitter taste.
Propyl gallate is a trihydroxybenzoic acid.
Propyl gallate is currently being studied in the clinical trial NCT01450098 (LY2484595 in healthy subjects).
Propyl gallate has been reported to be found in corn (Zea mays), glandular wood (Alchornea glandulosa), and mango (Mangifera indica), and relevant data are available.
Propyl gallate is present in corn. Propyl gallate is an antioxidant commonly used in foods, especially animal fats and vegetable oils. It has a synergistic effect with other antioxidants such as butylated hydroxyanisole (DNB28-K) and 2,6-di-tert-butyl-4-methylphenol (HCH42-H). It is particularly effective in polyunsaturated fats. Propyl gallate is an antioxidant that can be indirectly used as a food additive, derived from paper or cardboard packaging, adhesives, and food contact polymers. It protects the body from oxidative damage by hydrogen peroxide and oxygen free radicals through a catalytic mechanism similar to superoxide dismutase. Propyl gallate, also known as propyl 3,4,5-trihydroxybenzoate, is an ester formed by the condensation of gallic acid and propanol. It is an antioxidant added to oily foods to prevent oxidation. [Citation needed] As a food additive, its E number is E310.
Studies have shown that propyl gallate has pro-oxidative and free radical scavenging functions (A7908, A7909).
It can be used as an antioxidant in foods, fats, oils, ethers, emulsions, waxes, and transformer oils.

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Mechanism of Action
This study aimed to evaluate the anti-inflammatory activity and potential mechanism of action of propyl gallate (propyl gallate). This study used two animal models—a mouse acetic acid-induced permeability model and a rat air sac model—to demonstrate the anti-inflammatory activity of n-propyl gallate. It inhibited nitric oxide production and the induction of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. It reduced the level of reactive oxygen species in LPS-stimulated RAW264.7 macrophages. It also inhibited the gelatinase activity of matrix metalloproteinase-9 in LPS-stimulated RAW264.7 macrophages. It inhibited the degradation of inhibitory κBα in stimulated macrophages and enhanced the activity of the NF-κB promoter. It inhibited the phosphorylation of c-Jun N-terminal kinase 1/2 (JNK1/2) and the activity of the c-Jun promoter in stimulated macrophages. In summary, n-propyl gallate exerts its anti-inflammatory activity by downregulating the NF-κB and JNK pathways. In this study, we demonstrated that propyl gallate (PG) reduces the viability of THP-1, Jurkat, and HL-60 leukemia cells and induces apoptosis in THP-1 cells. PG activates caspases 3, 8, and 9 and increases the levels of p53, Bax, Fas, and Fas ligands. PG activates mitogen-activated protein kinase (MAPK), inhibits the nuclear translocation of nuclear factor E2-associated factor 2 (Nrf-2), and induces intracellular glutathione (GSH) depletion. Furthermore, PG increases superoxide dismutase-1 expression and reduces intracellular reactive oxygen species levels. Our data suggest that an early event in PG-induced apoptosis is MAPK/Nrf-2-mediated GSH depletion, and that PG induces apoptosis in human leukemia cells through multiple pathways. PG may be a potential chemotherapy drug or nutritional supplement for human leukemia patients.
Propyl gallate is a widely used antioxidant in the food, cosmetic, and pharmaceutical industries. It is approved for use as a food additive in many countries, typically in combination with other antioxidants such as BHA and BHT to provide synergistic effects. The compound is used to prevent oxidative rancidity in fats, oils, and fat-containing foods. It is also used in cosmetic products as an antioxidant and preservative. In research, Propyl gallate is used as a model antioxidant and as a tool to study oxidative stress and apoptosis. Its applications extend to fluorescence microscopy as an anti-fade reagent to reduce photobleaching of fluorescent dyes.

C10H12O5

212.2

212.068

121-79-9

4947

White to off-white solid powder

1.4±0.1 g/cm3

448.6±40.0 °C at 760 mmHg

146-149 °C(lit.)

181.3±20.8 °C

0.0±1.1 mmHg at 25°C

1.596

2.6

3

5

4

15

206

0

ZTHYODDOHIVTJV-UHFFFAOYSA-N

InChI=1S/C10H12O5/c1-2-3-15-10(14)6-4-7(11)9(13)8(12)5-6/h4-5,11-13H,2-3H2,1H3

propyl 3,4,5-trihydroxybenzoate

NSC-2626; NSC 2626; Propyl gallate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~1178.13 mM)

Solubility in Formulation 1: ≥ 6.25 mg/mL (29.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 6.25 mg/mL (29.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 6.25 mg/mL (29.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)