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| Phenolic acid found in gallnuts, sumac, witch hazel, tea leaves, oak bark. Has antioxidant, antimicrobial and anti-obesity properties. The GA derivatives include two types: ester and catechin derivatives. The most common ester derivatives of GA are alkyl esters, which are composed mainly of methyl gallate (MG), propyl gallate (PG), octyl gallate (OG), dodecyl gallate (DG), tetradecyl gallate (TG), and hexadecyl gallate (HG), and some of the main catechin derivatives are epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), gallocatechin gallate (GCG), and epigallocatechin gallate (EGCG) Gallic acid is a naturally occurring polyphenol found in a variety of plant-based foods. Some of the best dietary sources include: Fruits: Berries (strawberries, blackberries, blueberries) Grapes, including red wine (grapes are rich in polyphenols) Pomegranates and apples Nuts and Seeds: Walnuts and almonds have been noted to contain GA in their skins Herbs and Spices: Tea (especially green tea), Sumac and other spices Other Plants: Gallnuts (from oak trees) Pathways: -ROS generation in tumor cells is frequently reported, Antioxidant behavior dominates in normal tissue models -Apoptosis Induction: Activating caspase cascades, Shifting Bax versus Bcl-2, MMP, cyt-c release -Cell Cycle Arrest: typ @ G1 or G2/M checkpoints. -Anti-inflammatory Effects: inhibiting NF-κB -reported Angiogenesis Inhibition: -Modulation of Signaling Pathways: MAPK Pathway, PI3K/Akt Pathway Inhibition, p53 Pathway Gallic acid exhibits a complex behavior with ROS in cancer cells, acting as both an antioxidant and a pro-oxidant depending on the context and its concentration: Antioxidant Effects at Low Doses: -At lower concentrations, gallic acid is typically characterized by its ability to scavenge free radicals, thus reducing oxidative stress. This antioxidant property may help protect normal cells from DNA damage, reducing the risk of mutations that could lead to cancer. Pro-oxidant Effects at High Doses: >50-100uM? -Capable of biphasic redox behavior (antioxidant in normal cells, pro-oxidant in some tumor contexts) -At higher concentrations, GA can exert pro-oxidant effects, generating ROS within cancer cells. Elevated ROS levels can overwhelm the cellular antioxidant defenses of cancer cells, leading to oxidative stress, mitochondrial dysfunction, and ultimately cell death. Oral bioavailability is well absorbed but subject to rapid conjugation (glucuronide/sulfate/methylated metabolites). Many cytotoxic in-vitro concentrations are in the 10–100 µM range, often higher than typical plasma levels after dietary intake. Gallic acid — Gallic acid is a naturally occurring trihydroxybenzoic phenolic acid and plant secondary metabolite with antioxidant, pro-oxidant, anti-inflammatory, antimicrobial, and extensively studied preclinical anticancer activity. It is formally classified as a low-molecular-weight polyphenolic phenolic acid and is commonly abbreviated GA. Its chemical identity is 3,4,5-trihydroxybenzoic acid. Dietary and botanical sources include gallnuts, sumac, tea, grapes, berries, pomegranate, mango, walnuts, oak bark, and hydrolysable tannins. GA is also released during digestion or microbial metabolism of gallotannins and galloylated polyphenols. Its anticancer effects are strongly concentration-, cell-type-, redox-, and exposure-dependent. Primary mechanisms (ranked):
Bioavailability / PK relevance: GA can be absorbed orally and is among the more readily absorbed simple polyphenols, but absorption is followed by rapid methylation, glucuronidation, sulfation, microbial transformation, and urinary elimination. Circulating exposure consists substantially of conjugated and microbial metabolites rather than persistent free GA. Formulation strategies such as nanoparticles, conjugates, and encapsulation can increase exposure experimentally, but these delivery systems remain investigational. In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM GA, with pronounced pro-oxidant cytotoxicity frequently occurring toward the upper portion of this range or above it. These free-compound concentrations commonly exceed sustained plasma concentrations expected from ordinary dietary intake. Consequently, direct systemic anticancer effects demonstrated at high micromolar exposure may not be achievable through food consumption or conventional oral supplementation. Local gastrointestinal exposure, metabolites, tissue accumulation, or engineered delivery could produce different exposure relationships. Clinical evidence status: Preclinical. GA has extensive cell-culture evidence and a smaller body of animal evidence across multiple tumor types. Human pharmacokinetic and food-intervention studies confirm exposure to GA and its metabolites, but isolated GA has not established anticancer efficacy in randomized clinical trials and is not an approved cancer therapy. Human studies involving polyphenol-rich mango, pomegranate, tea, grape, or botanical preparations cannot be attributed specifically to GA. Therapy-sensitizing activity remains experimental and should not be used to justify combining GA supplements with chemotherapy outside clinical supervision. Gallic Acid Mechanistic Profile
P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”. Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria. The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health. In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways. The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria. The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation. |
| 7049- | GA, | Pharmacological effects of gallic acid in health and diseases: A mechanistic review |
| - | Review, | Var, | NA |
| 7043- | GA, | Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase |
| - | in-vitro, | Lung, | Calu-1 | - | in-vitro, | Lung, | A549 |
| 1624- | GA, | Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer |
| - | in-vitro, | Cerv, | NA |
| 1065- | GA, | Gallic acid, a phenolic acid, hinders the progression of prostate cancer by inhibition of histone deacetylase 1 and 2 expression |
| - | vitro+vivo, | Pca, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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