IngredientsEthyl gallate (EG), also called ethyl 3,4,5-trihydroxybenzoate, is a secondary metabolite that occurs naturally and may be found in a variety of fruits, vegetables, nuts, and plants. It is the ethyl ester of gallic acid. Its chemical formula is C9H10O5. The compound is registered under CAS number 831-61-8. Polyphenol gallates are secondary metabolites of plant origin, consisting of gallic acid esters.
Structurally, EG is a low molecular weight triphenolic compound, possessing both carboxylic acid and phenol-like properties, which contribute to its antioxidant and anti-inflammatory effects. The hydroxyl groups are mainly responsible for its radical scavenging activity.
Ethyl gallate is a food additive with E number E313. It is classified under the antioxidant category of food additives. The gallates have been used as food preservatives since 1948 to prevent formation of peroxides (which lead to rancidity) in oils, fats, and fat-containing foods.
Though found naturally in a variety of plant sources including walnuts, Terminalia myriocarpa, or chebulic myrobolan (Terminalia chebula), ethyl gallate can also be found in wine.
Ethyl gallate is a phenolic compound that is isolated from walnut kernels, Euphorbia fischeriana, and Galla rhois. Galla Rhois extract is a mixture of polygalloyl esters of glucose that contains gallotannins such as ethyl gallate, methyl gallate, and gallic acid. Ethyl gallate is a natural polyphenol found in a large number of medicinal plants and organic foods.
Additional documented botanical sources include Pistacia integerrima, and Acacia nilotica. Terminalia chebula can exhibit various kinds of pharmacological activities due to the presence of various kinds of phytoconstituents such as gallic acid, methyl gallate, and ethyl gallate. Shanyin Chaihu is the dried root of Gypsophila licentiana Hand.-Mazz., a plant which has a wide history of folk medicine. It can treat hepatitis and liver fever, and is the main raw material of GanWeiKangPian (a registered Chinese drug). Ethyl gallate has been identified as an active constituent isolable from this species. Results from studies using cultured cells and animals show that ethyl gallate can activate the production of prostaglandin E2, and the compound is richly contained in longan fruit.
Ethyl gallate is produced from gallic acid and ethanol. In industrial practice, esterification of gallic acid with ethanol under acid catalysis is the standard synthetic route, yielding a compound that can serve as either an isolated natural product (from botanical extraction) or a synthetically produced food-grade antioxidant. The compound is available as a pure reference standard.
Ethyl gallate is not itself a traditional medicine; rather, it is a constituent of plants and plant-derived preparations with long histories of use across multiple medical traditions. Its most documented traditional vehicle is Terminalia chebula, known in Ayurveda as Haritaki. Terminalia chebula is a member of the Combretaceae family. Known as the "king of medicines," Harad is among the oldest medicinal plants. Various medical systems, including Ayurveda, Siddha, Unani, and traditional Chinese medicine, have highlighted its therapeutic benefits.
T. chebula has been extensively used in Ayurveda, Unani, and homoeopathic medicine. The fruit has been used as a traditional medicine for a household remedy against various human ailments. Traditionally, T. chebula is used to cure chronic ulcer, gastritis, and stomach cancers. An ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) technique has been developed to measure the plasma levels of nine active compounds, including ethyl gallate, following the oral administration of T. chebula fruit extracts in rats, confirming that ethyl gallate is orally bioavailable from the fruit's preparations.
Terminalia chebula is a native medicinal plant of South Asian biodiversity including India, China, Bhutan, Cambodia, Thailand, and Nepal. It is one of the most widely used medicinally active plants in the Indian systems of medicine (i.e., Ayurveda, Unani, and Siddha) along with the Amchi system of medicine. Evaluation of decoctions along with final processed fermented formulations highlighted an increase in the amount of gallic acid, chebulic acid, ethyl gallate, and ellagic acid, suggesting that traditional fermentation processes may concentrate ethyl gallate in the final medicine.
Arjunarishta is an Ayurvedic cardioprotective polyherbal formulation. It is prepared by fermenting the decoction of the bark of Terminalia arjuna, fruits of Vitis vinifera, and flowers of Madhuca indica using flowers of Woodfordia fruticosa. Ethyl gallate has been identified by HPLC analysis as a constituent of such fermented Ayurvedic preparations.
Gypsophila licentiana Hand.-Mazz (Shanyin Chaihu in traditional Chinese medicine) possesses a history of use for the treatment of various diseases, including hepatitis. Ethyl gallate, the natural pharmacologically active ingredient of Shanyin Chaihu, exerts obvious pharmacological effects against inflammation.
Euphorbia fischeriana Steud is a traditional Chinese medicine that is known to possess a variety of anticarcinogenic properties. Ethyl gallate has been identified as a major bioactive constituent extracted from its roots.
In Brazil, ethnopharmacological studies show that Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz is commonly used in folk medicine as an antifungal, antimicrobial, and anti-inflammatory. In the Amazon region, the dried fruit powder of L. ferrea is widely used empirically by the population in an alcoholic tincture as an antimicrobial mouthwash in oral infections, and the infusion is also recommended for healing oral wounds. Ethyl gallate has been identified as a key constituent of L. ferrea extracts responsible for part of these properties.
Ethyl gallate was isolated and characterized as a mycobacteria-specific antibiotic from Haematoxylon campechianum as early as 1953, with bacteriostatic and bactericidal studies on Mycobacterium tuberculosis published in that same period in the Journal of Bacteriology.
Ethyl gallate is itself the active molecule under investigation; it is not a complex botanical extract but rather a defined phenolic ester. A naturally occurring ester of gallic acid, ethyl gallate has attracted interest because of its diverse range of pharmacological activities, which include anti-inflammatory, antioxidant, antibacterial, antiviral, and anticancer effects. Ethyl gallate is a phenolic acid derivative which has various potentials to modulate the host response to pathogens, such as via antioxidant activity, antibacterial activity, and inhibition of the production of cell adhesion factors.
The primary antioxidant mechanism of ethyl gallate is free-radical scavenging, attributable to its three phenolic hydroxyl groups. Ethyl gallate inhibits squalene epoxidase with an IC50 value of 4.2 µM for the rat enzyme. It scavenges DPPH radicals in a cell-free assay (IC50 = 4.96 µg/ml).
The relationship of EG to inflammation is complex and context-dependent. Based on observations that certain natural phenolic compounds can serve as reducing cosubstrates for cyclooxygenases (COXs), ethyl gallate can activate the production of prostaglandin E2, a representative prostaglandin. Computational analysis indicates that ethyl gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as a reducing cosubstrate. The effect of ethyl gallate is abrogated by galangin, which is known to bind to the same peroxidase active sites as a competitive inhibitor. The findings offer support for a hypothesis that the proinflammatory as well as health-beneficial effects of longan may be partly attributable to the activation of COX-1 and COX-2 by ethyl gallate.
Conversely, multiple preclinical studies have documented anti-inflammatory effects of EG. Ethyl gallate has significant characteristics including anti-inflammatory, antioxidant, and antiviral properties, positioning it as a potential candidate for therapeutic applications across several different illnesses, such as inflammatory conditions, cancer, and viral illnesses like influenza and herpes simplex. Preclinical studies have shown that it has the capacity to modulate inflammation and oxidative stress, both of which play significant roles in a variety of pathological diseases.
Several mechanistic pathways underlying EG's anticancer activity have been elucidated in preclinical models:
Ethyl gallate effectively inhibited bovine viral diarrhea virus (BVDV) infection by co-treatment and post-treatment in MDBK cells with noncytotoxic doses. EG suppressed BVDV infection at an early stage of the viral life cycle by blocking entry and replication steps but not viral attachment and release. Moreover, EG strongly inhibited BVDV infection by promoting interferon-induced transmembrane protein 3 (IFITM3) expression, which localized to the cytoplasm.
EG significantly reduced the levels of whitening-associated proteins, p-CREB, and p-PKA; it dose-dependently inhibited the expression of TYR, TRP-1, TRP-2, and transcription factor MITF. In addition, EG downregulated melanogenetic gene expression and activated autophagy signals. Therefore, EG could serve as a novel functional cosmetic material with antimelanogenic and autophagy-enhancing activity.
In silico molecular docking revealed ethyl gallate as an agonist of the α7 nicotinic receptor (α7nAChR). In silico ADME analysis showed effective penetration of EG in the CNS. EG reversed cognitive deficits in diabetic rats by reducing oxidative stress. EG enhances cholinergic transmission via α7nAChR to improve antioxidant defense and cognitive performance in diabetes.
Molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (−6.2 kcal/mol) and matrix metalloproteinase-9 (−4.6 kcal/mol), and unstable binding with tumor necrosis factor-α (−7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.
Important overarching note on evidence strength: Despite promising in vitro and animal model results, the clinical use of ethyl gallate remains unknown. The lack of human clinical studies leaves a significant vacuum in our findings, particularly regarding its safety, efficacy, and comprehensive pharmacological mechanisms. All evidence reviewed below is preclinical (in vitro cell studies, animal models, or in silico computational analyses) unless explicitly stated otherwise.
Ethyl gallate's antioxidant properties are among its most consistently documented characteristics across multiple experimental systems. It scavenges DPPH radicals in a cell-free assay (IC50 = 4.96 µg/ml). The mechanism relies on the donation of hydrogen atoms from the three hydroxyl groups of the galloyl moiety to reactive oxygen and nitrogen species. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of the oxidative stress marker lipid peroxidation have been observed in animal wound healing models treated with 1% EG ointment.
Evidence strength: Well-established in cell-free assays and animal models. No human data exist.
A preclinical study published in PubMed (PMID 30499613) employed in vitro kinase assays, cell-based assays, and a patient-derived xenograft (PDX) in vivo model. EG was reported to be a novel ERK1/2 inhibitor that suppresses esophageal cancer growth in vitro and in vivo. EG suppressed anchorage-dependent and -independent esophageal cancer cell growth. The results of in vitro kinase assays and cell-based assays indicated that EG directly binds to and inhibits ERK1 and ERK2 activities and their downstream signaling. The use of a PDX model (patient-derived xenograft) is a methodological strength of this particular study as it is closer to clinical relevance than standard cell lines, though still not a human clinical trial.
In a study using Galla Rhois-derived EG, it was demonstrated that EG has anticancer activity against a human leukemia cell line. Mechanistic studies show that EG acts on mitochondrial-dependent pathways and the caspase cascade to activate the intrinsic apoptotic pathway through expression of caspases-8, -9, and -3; AIF; and endonuclease G. EG inhibits the proliferation of, and induces apoptosis in, HL-60 leukemia cells when used at a concentration of 100 µM.
Results showed ethyl gallate obviously decreased cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner. Highly invasive MDA-MB-231 cells were found to be highly sensitive to treatment. The mechanistic pathway identified was Akt/NF-κB signaling.
Evidence strength for anticancer activity overall: Preliminary and exclusively preclinical (in vitro and animal models). No human clinical trials have been conducted or reported for any cancer type.
Preclinical studies have shown that EG has the capacity to modulate inflammation and oxidative stress, both of which play significant roles in a variety of pathological diseases. In a murine acute lung injury (ALI) model, EG was reported to attenuate injury through Nrf2 signaling. In the context of liver injury, EG was able to significantly decrease the liver coefficient, reduce the levels of ALT and AST in serum, and attenuate the expression levels of ROS, F4/80, and LY6G in liver tissue of mice, consistent with hepatoprotective and anti-inflammatory effects mediated through the RAS pathway.
The dual relationship with COX enzymes requires attention: computational analysis indicates that ethyl gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as a reducing cosubstrate; the effect of ethyl gallate is abrogated by galangin, which is known to bind to the same peroxidase active sites as a competitive inhibitor. This means EG may under certain conditions stimulate rather than inhibit prostaglandin synthesis, a context-dependent effect that distinguishes it from conventional NSAIDs.
Evidence strength: Preliminary, confined to cell culture and rodent models. No human evidence.
Multiple biological activities of EG have been reported, including antioxidant activity, antibacterial capacity, inhibition of the production of cell adhesion factors, and induction of apoptosis in cancer cells. Ethanolic extract, gallic acid, and ethyl gallate have antimicrobial and antibiofilm activities. Gallic acid and ethyl gallate reduce acidogenicity and aciduricity of Streptococcus mutans. Gallic acid and ethyl gallate promoted downregulation of glucosyltransferase genes in a biofilm model with relevance to dental caries.
The antimicrobial activity of EG against Mycobacterium tuberculosis was among the earliest documented findings, with bacteriostatic and bactericidal studies published in 1953 in the Journal of Bacteriology following isolation from Haematoxylon campechianum.
EG exhibited considerably effective antifungal activity with MIC <1,000 µg/ml against dermatophytic fungi in studies using EG isolated from Caesalpinia mimosoides. The fungi tested included Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum, Malassezia furfur, and Candida albicans.
Evidence strength: Preclinical (in vitro MIC studies). Historically documented mycobactericidal activity (1953 era research, in vitro and microbiological models). No human clinical antimicrobial trials.
EG effectively inhibited BVDV infection by co-treatment and post-treatment in Madin-Darby Bovine Kidney (MDBK) cells with noncytotoxic doses. EG suppressed BVDV infection at an early stage of the viral life cycle by blocking entry and replication steps but not viral attachment and release. Moreover, EG strongly inhibited BVDV infection by promoting IFITM3 expression, which localized to the cytoplasm. Other gallate derivatives with antiviral activity have been reported, such as epigallocatechin-3-gallate (EGCG) with potent inhibition against hepatitis virus, porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, and influenza virus. However, there is little research on the antiviral activity of EG specifically.
Evidence strength: Very preliminary. Predominantly in vitro, one animal-adjacent cell model (MDBK). No human data.
It has yet to be directly tested in experimental models whether EG possesses the ability to impede atherosclerosis development, and little is known about its potential mechanisms-of-action. Lipid accumulation and inflammation are hallmarks of early atherosclerotic lesion development. In one study, whether ethyl gallate had effects on these factors was evaluated using in vitro RAW264.7 macrophage models and in vivo zebrafish models. Furthermore, apoE−/− mice, a model of early lesion development characterized by fatty streak formation, were employed to verify the anti-atherosclerosis effects of EG.
In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish, and apolipoprotein (apo) E-deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also reduced.
Evidence strength: Preliminary, in vitro and animal models only. No human cardiovascular trials.
Cognitive decline, an important comorbidity of type 2 diabetes (T2D), is attributed to oxidative stress and impaired cholinergic signaling in the brain. The α7 nicotinic acetylcholine receptor (α7nAChR) is densely distributed in the hippocampus and cortex, and exerts neuroprotective and procognitive actions. Ethyl gallate, a natural phenolic antioxidant compound, showed high in-silico binding affinity towards α7nAChR and brain penetrability.
In silico molecular docking revealed ethyl gallate as an agonist of α7nAChR. In silico ADME analysis showed effective penetration of EG in the CNS. EG reversed cognitive deficits in diabetic rats by reducing oxidative stress.
Evidence strength: In silico modeling and one rodent (diabetic rat) model. No human neurocognitive data exist.
A Frontiers in Pharmacology study (2023; PMC10311562) employed bioassay-guided fractionation to isolate EG from Caesalpinia mimosoides Lam. and evaluate its wound-healing potential. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson's trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of the oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues.
Evidence strength: In vitro scratch wound assay plus Wistar albino rat in vivo model, with supporting in silico data. No human wound-healing trials.
The Castanopsis cuspidata var. sieboldii plant grows predominantly in temperate regions of Asian countries, such as South Korea. Research on this species has so far concentrated on the nutritional analysis, antioxidant activity, and anti-inflammation properties of its branches. The isolation of compounds and structural elucidation of effective single molecules was further explored, with this study demonstrating the antioxidant and antimelanogenic activity of a single substance of ethyl gallate isolated from CCS branch extracts.
EG significantly reduced the levels of whitening-associated proteins, p-CREB, and p-PKA; it dose-dependently inhibited the expression of TYR, TRP-1, TRP-2, and transcription factor MITF. In addition, EG downregulated melanogenetic gene expression and activated autophagy signals. Therefore, EG extracted from CCS branches could serve as a novel functional cosmetic material with antimelanogenic and autophagy-enhancing activity.
Evidence strength: In vitro (B16F10 melanoma cells) with kinase and molecular docking support. No human skin depigmentation data.
A study in Journal of Ethnopharmacology (2021) evaluated EG and gallic acid isolated from Libidibia ferrea against Streptococcus mutans in a biofilm model relevant to dental caries. The ethanolic extract, gallic acid, and ethyl gallate were evaluated for antibiofilm activities, and the influence of gallic acid and ethyl gallate on the expression of glucosyltransferase genes in S. mutans biofilms was also evaluated. Ethanolic extract, gallic acid, and ethyl gallate have antimicrobial and antibiofilm activities. Gallic acid and ethyl gallate reduce acidogenicity and aciduricity of Streptococcus mutans. Gallic acid and ethyl gallate promoted downregulation of glucosyltransferase genes.
Evidence strength: In vitro biofilm model. No human oral health trials.
As of the available published literature, there are no established or clinically validated human dosages for ethyl gallate as an isolated supplement or therapeutic agent. All dosages below are from preclinical studies only and are reported solely as documented in those sources.
Ethyl gallate as a pure isolated compound is available in research-grade and reference-standard preparations. It has not been formulated into or approved as a dietary supplement at a defined dose by any major regulatory body based on published literature.
Ethyl gallate is a food additive with E number E313, added to food as an antioxidant. Its use is authorized in certain food categories in Europe and other jurisdictions as an antioxidant preservative.
Gallic acid esters or gallates are antioxidants used as preservatives in food and cosmetics. Few cases of gallates causing allergic contact dermatitis (ACD) have been reported in the literature. Propyl, octyl, and dodecyl gallates are commonly used antioxidant preservatives with reports of associated allergic contact dermatitis. The objectives of one systematic review were to investigate the role of gallates in allergic contact dermatitis and to explore products containing these preservatives. Seventy-four cases of gallate contact allergy have been reported. In addition, a variety of commercially available cosmetic products and foods contain gallate chemicals. Propyl gallate is the most commonly reported gallate contact allergen and often causes facial and/or hand dermatitis. The contact sensitization data pertain primarily to propyl gallate (E310); ethyl gallate (E313) is a structural analog and cross-reactivity is plausible but the available systematic literature focuses on propyl, octyl, and dodecyl gallates.
Despite promising in vitro and animal model results, the clinical use of ethyl gallate remains unknown. The lack of human clinical studies leaves a significant vacuum in our findings, particularly of its safety, efficacy, and comprehensive pharmacological mechanisms. Future study is required to close this gap and establish the therapeutic value of ethyl gallate.
A notable safety-relevant pharmacological observation is that results from studies using cultured cells and animals show that ethyl gallate can activate the production of prostaglandin E2. Computational analysis indicates that ethyl gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as a reducing cosubstrate. This prostaglandin-stimulating activity is a relevant consideration in the context of inflammatory conditions, as it suggests that the net biological effect of EG on inflammation is not uniformly suppressive and may depend on dose, tissue context, and co-administered agents.
Ethyl gallate inhibits squalene epoxidase with an IC50 value of 4.2 µM for the rat enzyme. Squalene epoxidase is a key enzyme in the cholesterol biosynthesis pathway. The implications of this inhibition for long-term cholesterol metabolism in humans at concentrations achievable through dietary or supplemental intake are not characterized in human studies.
No specific chronic toxicology, carcinogenicity, or reproductive toxicity studies for ethyl gallate (E313) as a discrete compound are prominent in the published regulatory or peer-reviewed literature reviewed here. The EFSA regulatory framework has addressed propyl, octyl, and dodecyl gallates in formal scientific opinions; ethyl gallate's regulatory toxicology profile has not been similarly detailed in the sources identified. The absence of published human safety data is consistent with the compound's status as a food-contact and food-additive substance at low levels, rather than a pharmacological or supplemental dose agent with a characterized safety profile.
Preclinical research suggests that ethyl gallate could provide a diverse approach to disease treatment, particularly in cases where inflammation and oxidative stress are essential factors. However, the totality of the evidence base for ethyl gallate as a potential therapeutic agent is, as of the available literature, composed almost entirely of:
Despite promising in vitro and animal model results, the clinical use of ethyl gallate remains unknown. The lack of human clinical studies leaves a significant vacuum, particularly regarding safety, efficacy, and comprehensive pharmacological mechanisms. No randomized controlled trials, observational cohort studies, or systematic reviews of human clinical evidence have been identified in any area of application. The compound's status as a dietary supplement or nutraceutical agent in humans is not formally established or regulated.
Health conditions that Ethylgallate may help support.
Body systems that Ethylgallate may help support.
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