Trigalloyl glucose

Other Names

(2S,3R,4S,5R,6R)-3,5-dihydroxy-2-(3,4,5-trihydroxybenzoyloxy)-6-[(3,4,5-trihydroxybenzoyloxy)methyl]oxan-4-yl 3,4,5-trihydroxybenzoate(2S,3R,4S,5R,6R)-3,5-Dihydroxy-6-(((3,4,5-trihydroxybenzoyl)oxy)methyl)tetrahydro-2H-pyran-2,4-diyl bis(3,4,5-trihydroxybenzoate)1,3,6-Tri-O-galloyl glucose1,3,6-Tri-O-galloyl-beta-D-glucopyranose1,3,6-Tri-O-galloyl-beta-D-glucose1,3,6-Tri-O-galloyl-β-D-glucopyranose1,3,6-Tri-O-galloyl-β-D-glucose1,3,6-Tri-O-galloylglucose1,3,6-Trigalloyl glucose1,3,6-Trigalloyl β-D-glucose1,3,6-Trigalloylglucose1,3,6-tris(3,4,5-trihydroxybenzoate)β-D-glucopyranose1,3,6-Tris-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranosebeta-D-Glucopyranose 1,3,6-trigallateGallotanninNP 005114NSC 69861β-D-Glucopyranose 1,3,6-trigallateβ-D-Glucopyranose, 1,3,6-tris(3,4,5-trihydroxybenzoate)

Synopsis

Trigalloyl Glucose: A Comprehensive Encyclopedic Reference

1. Identity and Chemical Characterization

1.1 Nomenclature and Structural Forms

Trigalloyl glucose is the common collective name for a family of closely related hydrolyzable gallotannin compounds in which three galloyl (3,4,5-trihydroxybenzoyl) ester groups are covalently bound to the hydroxyl positions of a central β-D-glucopyranose (glucose) molecule. Because the glucose core possesses five available hydroxyl positions, multiple positional isomers exist; the most thoroughly characterized and cited in the phytochemical literature are 1,3,6-trigalloyl glucose (also written 1,3,6-tri-O-galloyl-β-D-glucose), 1,2,6-trigalloyl glucose (1,2,6-tri-O-galloyl-β-D-glucose), and 1,2,3-trigalloyl glucose.

1,3,6-Trigalloylglucose, or more specifically 1,3,6-tri-O-galloyl-β-D-glucose, is a gallotannin. 1,2,6-Trigalloylglucose, or more specifically 1,2,6-tri-O-galloyl-β-D-glucose, is a gallotannin found in cell cultures of Cornus officinalis.

Synonyms for 1,3,6-trigalloyl glucose include: 1,3,6-tri-O-galloyl-β-D-glucopyranose; 1,3,6-tri-O-galloylglucose; 1,3,6-tris(3,4,5-trihydroxybenzoate) β-D-glucopyranose; and Gallotannin (CAS RN 18483-17-5).

The molecular formula for these trigalloyl glucose isomers is C₂₇H₂₄O₁₈. Gallotannin is a class of hydrolysable tannins obtained by condensation of the carboxy group of gallic acid (and its polymeric derivatives) with the hydroxy groups of a monosaccharide, most commonly glucose.

1.2 Classification within the Tannin Family

Tannins can be divided into two vital groups, hydrolysable and condensed tannins, according to their structure and properties. Hydrolysable tannins are composed of esters of gallic acid (gallotannins) or ellagic acid (ellagitannins) with a sugar core, usually glucose, and are readily hydrolyzed by acids or enzymes into monomeric products.

Gallotannins are large polyphenolic compounds consisting of glucose esterified to gallic acid, and occur in approximately 18% of all dicotyledonous plants — they play important roles in defense against attack by bacteria, fungi, or herbivores. Trigalloyl glucose isomers are lower-substitution members of the gallotannin series, positioned structurally between digalloyl glucose and tetragalloyl glucose, and function as biosynthetic intermediates on the pathway to fully galloylated pentagalloyl glucose (PGG), the most abundant and studied gallotannin.

1.3 Physical Properties and Common Preparation Forms

1,3,6-Trigalloyl β-D-glucose is a primary reference substance with certified absolute purity (considering chromatographic purity, water, residual solvents, and inorganic impurities), and is soluble in acetone, methanol, and hot water. In research and analytical contexts it is commercially available as a highly purified dry powder or dissolved reference standard, typically obtained via solvent extraction from plant material followed by chromatographic isolation. The compound is also amenable to laboratory chemical synthesis through esterification of β-D-glucose with gallic acid.

2. Natural Sources and Botanical Origins

2.1 Principal Plant Sources

Trigalloyl glucose isomers are distributed across numerous plant families. The most specifically documented botanical sources are:

Terminalia chebula Retz. (Combretaceae) — 1,3,6-Trigalloylglucose can be found in Paeonia lactiflora and Terminalia chebula. The species T. chebula, T. bellerica and T. horrida are rich sources of gallic acid and other simple gallate esters like methyl gallate, 1,6-di-galloyl-β-D-glucose, 3,4,6-tri-galloyl-β-D-glucose, 1,3,4,6-tetra-galloyl-β-D-glucose and 1,2,3,4,6-penta-galloyl-β-D-glucose.
Paeonia lactiflora Pall. (Paeoniaceae) — In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1,200 years. Both 1,2,6- and 1,3,6-trigalloyl glucose isomers are among the phytochemical constituents of this species.
Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) — From the AcOEt extract of the seeds of Picrorhiza kurroa were isolated, among other compounds, 1-O,3-O,6-O-trigalloyl-β-D-glucose and 1-O,2-O,3-O,4-O,6-O-pentagalloyl-β-D-glucose, and their structures were established by extensive NMR and chemical studies.
Cornus officinalis Siebold & Zucc. (Cornaceae) — 1,2,6-Trigalloylglucose is a gallotannin found in cell cultures of Cornus officinalis.
Chrozophora oblongifolia (Euphorbiaceae) — Chemical investigation of C. oblongifolia aerial parts resulted in the isolation of, among other compounds, 1,3,6-trigalloyl glucose.
Trapa species (Lythraceae/Trapaceae) — A total of 29 substances were identified and quantified in water caltrop (Trapa quadrispinosa Roxb.) husk extract, and tannins were the main constituents. Trigalloyl glucose isomers are among the galloylglucose tannins specifically identified in Trapa japonica pericarp extracts, alongside digalloyl, tetragalloyl, and pentagalloyl glucose derivatives.

More broadly, the metabolic sequence in plants follows the order: β-glucogallin → 1,6-digalloylglucose → 1,2,6-trigalloylglucose → 1,2,3,6-tetragalloylglucose → 1,2,3,4,6-pentagalloylglucose. This means trigalloyl glucose isomers are present — at least transiently — in any plant that synthesizes higher-order gallotannins such as PGG, making their wider occurrence in oaks (Quercus spp.), sumac (Rhus spp.), pomegranate (Punica granatum), and many related species a reasonable inference from the biosynthetic literature, though direct isolation and specific quantification at the trigalloyl stage varies by species and study.

3. Traditional and Historical Use

3.1 Terminalia chebula — Ayurvedic, Tibetan, and East Asian Traditions

The fruit of Terminalia chebula (known in Sanskrit as haritaki and in Tibetan medicine as one of the "three fruits") has among the longest documented records of use of any plant harboring trigalloyl glucose. T. chebula Retz., native to South and Southeast Asia, is highly regarded in both Tibetan and Ayurvedic medicine. It is a medium-to-large-sized tree belonging to the Combretaceae family, and its dried fruit is extensively used, especially in China, Nepal, India, Myanmar, Sri Lanka, Thailand, and Bangladesh. It is celebrated as the "king of Tibetan medicines" and is consistently named first in the Ayurvedic Materia Medica.

The plant, known for its dried fruit — Chebulae Fructus — is a medicinal plant with a long-standing global reputation that was initially recognized for its therapeutic properties during the Jin Dynasty. Current reviews consolidate knowledge on its traditional uses, phytochemistry, and pharmacological properties.

Terminalia chebula Retz., commonly known as 'Haritaki/Myrobalan', has been utilised as a traditional medicine for a long time, and has been extensively exercised in various indigenous medicine practices like Unani, Tibb, Ayurveda, and Siddha to remedy human ailments such as bleeding, carminative action, dysentery, as a liver tonic, digestive aid, antidiarrheal, analgesic, anthelmintic, antibacterial, and for skin disorders.

Preparations of T. chebula fruit were and are made predominantly as water decoctions, powdered fruit, and multi-herb formulations (such as the classic Ayurvedic preparation triphala, in which haritaki is combined with amalaki and bibhitaki). These preparations contain complex mixtures of tannins, of which trigalloyl glucose isomers form a fraction alongside the major ellagitannins (chebulagic acid, chebulinic acid, corilagin) and galloyl esters.

3.2 Paeonia lactiflora — Chinese, Korean, and Japanese Medicine

In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1,200 years. A water/ethanol extract of the root is now known as total glucosides of peony (TGP), which contains more than 15 components; paeoniflorin is the most abundant ingredient and accounts for the pharmacological effects observed with TGP in both in vitro and in vivo studies. Trigalloyl glucose co-occurs with paeoniflorin and other peony glycosides and tannins in roots of this species.

3.3 Picrorhiza kurroa — Ayurvedic Tradition

Picrorhiza kurroa, known in Ayurvedic medicine as kutki, is a small perennial herb native to the alpine Himalayas and has been used for centuries in traditional Ayurvedic and Tibetan formulations as a hepatoprotective, anti-inflammatory, antipyretic, and immunomodulatory agent. Extracts were prepared from the rhizome and, to a lesser extent, the seeds. The seeds were identified more recently as a notable source of trigalloyl glucose.

3.4 Trapa Species — East and Southeast Asian Food and Medicine

Trapa bispinosa Roxb. is a traditional Chinese food well known for its medicinal properties. The pericarp (shell) of water caltrop species has been used in Chinese folk medicine for conditions including digestive complaints, and the tannin-rich husks have been studied in relation to antioxidant and antidiabetic activities.

3.5 Historical Tanning and Industrial Use of Gallotannins

Gallotannins, characterized with the glycosidic core and galloyl unit, are vital components of hydrolyzable tannins. Research over the past century has drawn back the curtains on gallotannins to reveal rich vistas. Since the first disclosure in the 1900s, gallotannins have attracted considerable attention. Initially applied in the tanning of leather, the discovery of their antioxidant effect and additional reaction mechanisms has led to increasing application of gallotannins in food, medicine, feed, cosmetics, and other fields.

4. Biosynthesis and Biochemistry

4.1 Biosynthetic Pathway in Plants

Trigalloyl glucose isomers are obligate biosynthetic intermediates in the gallotannin pathway of higher plants. The biosynthesis of hydrolyzable tannins is initiated by the formation of gallic acid from the shikimate pathway intermediate 3-dehydroshikimic acid, catalyzed by bifunctional dehydroquinate dehydratase/shikimate dehydrogenases (DQD/SDHs). In the second step, UDP glycosyltransferases (UGTs) esterify gallic acid with glucose to form β-glucogallin (1-O-galloyl-β-D-glucose).

Further substitution of glucose hydroxyls is not randomly distributed in these conversions but displays an unexpected extreme specificity, thus constituting the metabolic sequence β-glucogallin → 1,6-digalloylglucose → 1,2,6-trigalloylglucose → 1,2,3,6-tetragalloylglucose → and finally 1,2,3,4,6-pentagalloylglucose. In those reactions, β-glucogallin exerts a dual role, functioning not only as an acyl acceptor but also as an efficient acyl donor.

Without any other cofactors, the transformation of β-glucogallin, formed in situ, to di- and trigalloylglucose was catalyzed by galloyltransferase enzymes. β-glucogallin was deemed to function not only as acyl acceptor, but also as efficient acyl donor.

Immunohistochemical studies have shown that leaf mesophyll cell walls are the typical site of origin and deposition of hydrolyzable tannins. With extreme regularity, substitution of glucose hydroxyls is not randomly distributed in these conversions.

4.2 Relationship to Gallic Acid

Upon hydrolysis — which may occur under acidic conditions in the stomach, through intestinal esterases, or via microbial enzymes in the gut — trigalloyl glucose releases three molecules of gallic acid (3,4,5-trihydroxybenzoic acid) and one molecule of glucose. Gallic acid itself is a well-characterized phenolic compound with documented antioxidant, anti-inflammatory, and antimicrobial properties, and is widely considered to be a principal hydrolysis product responsible for part of the biological activity observed with gallotannins. Trigalloylglucose is functionally related to gallic acid.

Gallotannins, including galloylglucoses, release gallic acid upon hydrolysis, whereas ellagitannins contain a hexahydroxydiphenoyl (HHDP) group and produce ellagic acid when hydrolyzed.

5. Key Constituents and Mechanisms of Action

5.1 Structure–Activity Considerations

The biological activities of trigalloyl glucose derive from the combination of its polyhydroxylated aromatic (galloyl) moieties and the central glucose scaffold. The multiple catechol-like triol groups on each galloyl unit confer potent electron-donating and free-radical-quenching capacity. The ester linkages, unlike the carbon-carbon bonds of condensed tannins, make the molecule susceptible to enzymatic and acid hydrolysis. Hydrolysable tannins are composed of esters of gallic acid with a sugar core, usually glucose, and are readily hydrolyzed by acids or enzymes into monomeric products.

The specific positional arrangement of the three galloyl groups distinguishes the various isomers from one another with respect to both solubility and receptor/enzyme binding geometry. Cannell et al. isolated an isomer of PGG, 3-O-digalloyl-1,2,6-trigalloylglucose, from the freshwater green alga Spirogyra varians, and found that this compound irreversibly inhibited α-glucosidase and was more potent than PGG, 1,2,3,6-tetra-O-galloylglucose, or 1,2,6-tri-O-galloylglucose. This indicates that the degree and position of galloylation critically shape biological potency.

5.2 Antioxidant and Free-Radical Scavenging

The three trihydroxybenzoyl groups endow trigalloyl glucose with substantial free-radical scavenging capacity, attributable to the abundant phenolic hydroxyls that readily donate hydrogen atoms or electrons to neutralize reactive oxygen species (ROS). This activity has been measured in multiple in vitro systems. Compounds isolated from Picrorhiza kurroa seeds, including 1,3,6-trigalloyl-β-D-glucose, showed 50.5% inhibition of lipid peroxidation at 5 μg/mL. For context, the commercial antioxidants BHA, BHT, and TBHQ inhibited lipid peroxidation by 85.6%, 87.1%, and 81.1%, respectively, at concentrations of 1.8, 2.2, and 1.66 μg/mL.

The isolated metabolites from Chrozophora oblongifolia were tested for their antioxidant and advanced glycation end-products (AGEs) formation, α-glucosidase, and lipase inhibitory activities, and 1,3,6-trigalloyl glucose exhibited the highest activity as an antioxidant and AGEs inhibitor as well as an α-glucosidase inhibitor.

5.3 Cyclooxygenase (COX) Inhibition

It was observed that pentagalloyl glucose (bPGG), O-trigalloyl-beta-D-glucose (gallotannin), and isocorilagin (ellagitannin) inhibited the activity of COX-1 isolated from ram seminal vesicles, as established by measuring O₂ consumption during the transformation of arachidonic acid (AA) to endoperoxide catalyzed by COX-1. This in vitro result points to a potential prostaglandin-suppressing mechanism, although it has not been confirmed in human clinical studies.

5.4 α-Glucosidase Inhibition and Antidiabetic Mechanisms

Polyphenols are major plant constituents that exert antidiabetic activity through different mechanisms, including radical scavenging activity, regulation of glucose uptake, and inhibition of fat and polysaccharide hydrolysis in addition to their inhibitory role regarding the formation of advanced glycation end products (AGEs).

1,3,6-Trigalloyl glucose exhibited the highest activity as an α-glucosidase inhibitor among compounds isolated from C. oblongifolia, and showed promising binding affinity and stability towards the human intestinal maltase-glucoamylase α-glucosidases, as revealed through coupled molecular docking and dynamics studies.

The 1,2,6-trigalloylglucose and α-glycosidase complex showed better root mean square deviation (RMSD) stability in molecular dynamics simulation. These results may provide a good potential natural resource for the improvement of oxidative stress injury and blood glucose control in diabetes mellitus.

5.5 Protein-Binding and Astringent Properties

Like other gallotannins, trigalloyl glucose is capable of non-covalently binding to proteins through hydrogen bonding and hydrophobic interactions with proline-rich domains, causing protein precipitation and conformational changes. Plant tannins are water-soluble polyphenolic compounds that can bind and/or precipitate proteins and metals. This fundamental property underlies their astringent taste in food contexts and also underpins several proposed pharmacological mechanisms (e.g., antidiarrheal activity via mucosal protein crosslinking, antimicrobial activity via bacterial enzyme inhibition).

6. Scientific Evidence by Area of Use

6.1 Antioxidant and Anti-Lipid-Peroxidation Activity

Evidence level: Preliminary; in vitro and cell-based data only. No human clinical trials identified.

The antioxidant activity of 1,3,6-trigalloyl glucose was established in a phytochemical isolation study of Picrorhiza kurroa seeds, published in Chemistry & Biodiversity (2004). From the AcOEt extract of the seeds of Picrorhiza kurroa were isolated 1-O,3-O,6-O-trigalloyl-β-D-glucose and other tannins, with structures established by extensive NMR and chemical studies. All isolated compounds showed dose-dependent inhibition of lipid peroxidation at 5 μg/mL, with 1,3,6-trigalloyl glucose (compound 10) exhibiting 50.5% inhibition. This was a purely in vitro biochemical assay; no animal or human data on this compound's antioxidant activity are available.

In a separate 2022 in vitro study (published in Biology, MDPI; PMC9139161), 1,3,6-trigalloyl glucose isolated from Chrozophora oblongifolia demonstrated the highest antioxidant activity among five isolated phenolic compounds, also outperforming the other isolates in AGE formation inhibition. The evidence base is confined to cell-free and cell-based assays; no in vivo or clinical validation of the antioxidant activity of the isolated trigalloyl glucose compound has been published.

6.2 Antidiabetic Activity (α-Glucosidase Inhibition and AGE Inhibition)

Evidence level: Preliminary; in vitro and in silico only. No animal or human trials on the isolated compound identified.

Two key published studies specifically address the antidiabetic potential of trigalloyl glucose isomers as isolated compounds:

Abdallah et al. (2022), Biology (MDPI), PMC9139161: Chemical investigation of C. oblongifolia aerial parts resulted in the isolation of five major compounds including 1,3,6-trigalloyl glucose. The isolated compounds were tested for their antioxidant and AGEs formation, α-glucosidase, and lipase inhibitory activities. 1,3,6-Trigalloyl glucose exhibited the highest activity as an antioxidant and AGEs inhibitor as well as an α-glucosidase inhibitor, and showed promising binding affinity and stability towards the human intestinal maltase-glucoamylase α-glucosidases, as revealed through coupled molecular docking and dynamics studies. Limitations: This was a purely in vitro and computational study; no cell-based uptake assays or animal models were included, and no clinical data exist.
Water caltrop (Trapa quadrispinosa) study (2022), Nutrients, PMC9598876: A total of 29 substances were identified and quantified in this study, and tannins were the main constituents of water caltrop husk extract. The 1,2,6-trigalloylglucose and α-glycosidase complex showed better RMSD stability via molecular dynamics simulation study. The study demonstrated in vitro α-glucosidase inhibitory activity from tannin-rich fractions, with 1,2,6-trigalloylglucose specifically highlighted through computational modeling as a stable enzyme–inhibitor complex. Limitations: The inhibitory IC₅₀ values reported were for the whole phenolic fraction, not for isolated 1,2,6-trigalloyl glucose alone; translation to clinical outcomes has not been tested.

6.3 Anti-Inflammatory and COX Inhibitory Activity

Evidence level: In vitro only (enzyme assay). No animal or clinical data for the isolated compound.

It was observed that pentagalloyl glucose (bPGG), O-trigalloyl-beta-D-glucose (gallotannin), and isocorilagin (ellagitannin) inhibited the activity of COX-1 isolated from ram seminal vesicles. This effect was established by measuring O₂ consumption during the transformation of arachidonic acid to endoperoxide catalyzed by COX-1. The study, by Zhang et al. (2004) using Picrorhiza kurroa seed extracts, demonstrated COX-1 inhibition for the trigalloyl glucose fraction in an isolated enzyme assay — a relevant mechanistic finding, but one not extended to in vivo or human inflammation models. No clinical trials have assessed the anti-inflammatory effect of trigalloyl glucose in isolation.

6.4 Antimicrobial Activity

Evidence level: Preliminary; limited in vitro data for the compound class; no specific clinical data for isolated trigalloyl glucose.

Gallotannins as a class, including trigalloyl glucose-containing plants and extracts, have demonstrated antimicrobial properties in vitro. Zhang et al. studied the antibacterial activity of Acer truncatum Bunge extract and found that pentagalloyl glucose (PGG) inhibited several bacterial strains such as Staphylococcus aureus, Staphylococcus epidermidis, E. coli, and Pseudomonas aeruginosa with MIC values at 0.25, 0.06, 0.25, and 0.125 mg/mL, respectively. The inhibitory mechanism proposed was related to inhibition of the bacterial type II fatty acid synthesis system. While these data pertain to PGG (pentagalloyl glucose) rather than trigalloyl glucose specifically, the shared structural motifs and the biochemical literature suggest the class broadly inhibits microbial enzymes. Direct, isolated-compound antimicrobial data for trigalloyl glucose per se are limited and mostly appear as part of extract studies.

6.5 Hepatoprotective Activity of the Gallotannin Class

Evidence level: Animal model data available for gallotannin extracts; no human clinical data for isolated trigalloyl glucose.

To investigate toxicity, protective effects, and action mechanisms of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in ICR mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured. The GEGR/CCl₄-treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity. Necrotic area indicating hepatic cell death was significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR pre-administered group. This study investigated a gallotannin-enriched extract and not isolated trigalloyl glucose. Specific hepatoprotective data for isolated trigalloyl glucose are unavailable.

6.6 Traditional Medicine Context: Terminalia chebula

Studies have identified approximately 149 compounds within Terminalia chebula fruit, including tannins, phenolic acids, lignans, triterpenes, flavonoids, and volatiles. These compounds confer a broad spectrum of biological activities in vitro and in vivo, such as antioxidant, anti-inflammatory, antiviral, anticancer, antibacterial, hepatoprotective, nephroprotective, neuroprotective, and anti-diabetic activities, some of which are already integrated into clinical practice. However, it must be emphasized that this body of evidence pertains to the whole fruit extract and its complex phytochemical mixture; the contribution of trigalloyl glucose isomers specifically to these effects has not been individually characterized in clinical trials.

6.7 Human/Clinical Evidence — Overall Assessment

At the time of writing, no randomized controlled trials, prospective human studies, or systematic reviews exist that evaluate isolated trigalloyl glucose (any isomer) as a standalone intervention in human subjects. All mechanistic and bioactivity data are derived from in vitro enzyme assays, cell culture systems, computational (in silico) molecular docking, and — in the case of the parent plants — animal studies or clinical data using complex, multi-compound extracts. This is a significant evidence gap. The compound remains at an early-stage, preclinical investigation phase.

7. Body Systems and Health Areas of Association

Based on the published in vitro and in silico evidence, trigalloyl glucose isomers have been studied or discussed in relation to the following body systems and health domains:

Endocrine / Metabolic system: α-glucosidase inhibition (potential postprandial glucose lowering), AGE inhibition (potential relevance to diabetic complications), lipase inhibition (potential relevance to fat absorption).
Cardiovascular / Inflammatory system: COX-1 inhibitory activity (potential prostaglandin modulation); antioxidant protection against lipid peroxidation, relevant to atherosclerosis pathways.
Hepatic system: Gallotannin extracts from related plants have shown hepatoprotective activity in animal models; gallic acid (the hydrolysis product) is independently documented for hepatoprotection.
Gastrointestinal system: The astringent, protein-binding properties of gallotannins underlie traditional use for diarrhea, dysentery, and gastrointestinal inflammation in T. chebula and peony root traditions.
Immunological / Rheumatological system: Paeonia lactiflora root extracts (which contain trigalloyl glucose as a component) have been used for rheumatoid arthritis and lupus, though the pharmacological credit belongs primarily to paeoniflorin rather than tannin fractions.
Antimicrobial: Broad-spectrum enzyme inhibitory activity against bacterial and fungal targets noted in vitro for the gallotannin class.

8. Dosage Forms and Doses Reported in Studies

No established therapeutic dose exists for trigalloyl glucose as an isolated compound, as no human clinical dosing studies have been conducted. Dose information available in the literature is limited to in vitro assay concentrations:

Lipid peroxidation inhibition assay (Picrorhiza kurroa study, 2004): Compounds were tested at 5 μg/mL, at which concentration 1,3,6-trigalloyl-β-D-glucose (compound 10) showed 50.5% inhibition of lipid peroxidation.
α-Glucosidase inhibition and antioxidant assays (Chrozophora oblongifolia study, 2022): Specific IC₅₀ values for 1,3,6-trigalloyl glucose in α-glucosidase and AGE inhibition assays were reported in the full publication; the abstract confirms it was the highest-activity compound among the five isolates at the tested concentrations, with in silico modeling used to rationalize binding.
Water caltrop fraction study (2022): All phenolic fractions of water caltrop husk exhibited antioxidant activities. The bound phenolic fraction had the highest radical scavenging ability with IC₅₀ values of 0.82 ± 0.12 μg/mL (ABTS) and 1.15 ± 0.02 μg/mL (DPPH), while the free phenolic fraction showed the strongest α-glycosidase inhibition with an IC₅₀ value of 1.43 ± 0.12 μg/mL. These are fraction-level (not isolated trigalloyl glucose-level) values.

The compound is commercially available as a purified analytical reference standard and research reagent at the milligram scale for laboratory use. No standardized supplement or pharmaceutical preparation based on isolated trigalloyl glucose has been established. Preparations of source plants (T. chebula, P. lactiflora) used in traditional systems contain trigalloyl glucose as a minor constituent within a complex phytochemical matrix; dosing of these preparations reflects traditional or modern clinical use of the whole plant extract, not the isolated compound.

9. Safety Considerations and Interactions

9.1 Class-Level Safety of Gallotannins

Tannins show notable pharmacological properties that are beneficial to human health. Some tannin-rich plant extracts have also been shown to be effective in clinical trials, such as green tea, phytopreparations of grape seeds, and polyphenol-rich cocoa. Tannic acid, the simplest hydrolysable tannin, is a US Food and Drug Administration (FDA)-approved food additive.

At very high concentrations, tannins as a class are associated with protein precipitation in biological tissues. Tannic acid causes failure of breathing, inflammation of the stomach, and tissue death of the liver, and kidney inflammation at toxic doses. At sufficiently high doses the material may be hepatotoxic. These toxicity findings, however, pertain to concentrated tannic acid (a complex mixture of polygalloyl glucoses) at non-physiological doses. No specific toxicity data for isolated trigalloyl glucose in animals or humans have been published.

9.2 Potential Nutrient Interactions

Gallotannins and hydrolyzable tannins broadly are recognized to bind dietary minerals — particularly iron, zinc, and calcium — through complex formation with their phenolic hydroxyls. Consumption of tannin-rich plant preparations has been documented to reduce non-heme iron bioavailability in the diet when consumed alongside iron-containing foods. This interaction is a class effect of polyphenolic tannins and has not been specifically studied for trigalloyl glucose in isolation. Regular high-dose supplementation with tannin-rich plants in individuals at risk of iron deficiency merits nutritional consideration.

9.3 Protein-Binding Properties

Plant tannins are water-soluble polyphenolic compounds that can bind and/or precipitate proteins and metals. This property may theoretically affect the bioavailability of co-administered proteinaceous compounds or reduce the activity of digestive enzymes when tannins are consumed in high concentration, though the clinical significance of this effect at the levels of trigalloyl glucose present in normal food or supplement doses has not been quantified.

9.4 Bioavailability and Metabolism

No pharmacokinetic studies specifically tracking the absorption, distribution, metabolism, and excretion (ADME) of trigalloyl glucose isomers in humans or animals have been published. By analogy with the well-studied gallotannin pentagalloyl glucose and with gallic acid (the principal hydrolysis product), it is expected that trigalloyl glucose would be subject to hydrolysis by intestinal esterases and colonic microbiota, yielding gallic acid and glucose. Gallic acid has documented oral bioavailability and undergoes further microbial transformation to pyrogallol and related metabolites. Whether intact trigalloyl glucose crosses the intestinal epithelium is unknown.

9.5 Absence of Clinical Safety Data

Because no clinical studies have been conducted with isolated trigalloyl glucose, no dose-response safety data, tolerability profiles, drug interaction studies, or observations in special populations (pregnancy, pediatric, hepatic or renal impairment) are available. Any safety assessment of the compound in isolation therefore cannot be made on a clinical evidence basis and must extrapolate from the broader tannin class and the source plant literature.

10. Evidence Summary and Research Gaps

Trigalloyl glucose isomers are botanically widespread, biosynthetically fundamental gallotannin intermediates found in medicinal plants with deep traditions of use across Ayurvedic, Tibetan, Chinese, Korean, and Japanese medicine. The compound has a clearly defined chemical identity, and multiple positional isomers (1,2,6-, 1,3,6-, 1,2,3-) have been isolated and structurally characterized from botanically and geographically diverse plant species.

Scientific investigation of isolated trigalloyl glucose is early stage. Available data are limited to:

In vitro enzyme assays demonstrating α-glucosidase inhibition, COX-1 inhibition, lipid peroxidation inhibition, and AGE formation inhibition.
Computational (in silico) molecular docking studies showing binding affinity and stability at enzyme active sites.
Phytochemical isolation and characterization from source plants.

No animal efficacy or toxicity studies, and no human clinical trials, have been published for trigalloyl glucose as an isolated compound. The traditional medicine evidence base belongs to the complex plant preparations in which trigalloyl glucose is one of many biologically active constituents, making attribution of specific effects to this compound alone impossible from the current literature. This distinction between the traditional evidence base (plant extracts) and the scientific evidence base (isolated compound) must be clearly maintained.

References

Health Conditions

Health conditions that Trigalloyl glucose may help support.

No conditions available.

Body Systems

Body systems that Trigalloyl glucose may help support.

No body systems available.