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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 |
| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 7040- | GA, | Effects of gallic acid on acrylamide-induced endoplasmic reticulum stress, neuroinflammation and neuronal apoptosis in rats |
| - | Trial, | AD, | NA |
| - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | DU145 |
| 7036- | TBE, | GA, | Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS-Induced Inflammation and Oxidative Stress via MAPK/NF-κB and Akt/AMPK/Nrf2 Pathways |
| - | in-vitro, | Nor, | THP1 | - | in-vitro, | Nor, | RAW264.7 |
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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