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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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| Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases. Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer. Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Catalase and Cancer Oxidative Stress and Cancer: Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis. Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells. Expression Levels in Different Cancers: Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior. Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis. Prognostic Implications: Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress. Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched). |
| 7049- | GA, | Pharmacological effects of gallic acid in health and diseases: A mechanistic review |
| - | Review, | Var, | NA |
| 7040- | GA, | Effects of gallic acid on acrylamide-induced endoplasmic reticulum stress, neuroinflammation and neuronal apoptosis in rats |
| - | Trial, | AD, | NA |
| 7035- | GA, | Gallic acid attenuates LPS-induced inflammation in Caco-2 cells by suppressing the activation of the NF-κB/MAPK signaling pathway |
| - | in-vitro, | IBD, | Caco-2 |
| - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | DU145 |
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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