Description: <b>Phenolic acid</b> found in gallnuts, sumac, witch hazel, tea leaves, oak bark. Has anitoxidant, antimicrobial and anti-obesity properties.<br>
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)<br>
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Gallic acid is a naturally occurring polyphenol found in a variety of plant-based foods. Some of the best dietary sources include:<br>
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Fruits:<br>
Berries (strawberries, blackberries, blueberries)<br>
Grapes, including red wine (grapes are rich in polyphenols)<br>
Pomegranates and apples<br>
Nuts and Seeds: Walnuts and almonds have been noted to contain GA in their skins<br>
Herbs and Spices: Tea (especially green tea), Sumac and other spices<br>
Other Plants: Gallnuts (from oak trees)<br>
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Pathways:<br>
-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. <br>
-Anti-inflammatory Effects: inhibiting NF-κB <br>
-reported Angiogenesis Inhibition:<br>
-Modulation of Signaling Pathways: MAPK Pathway, PI3K/Akt Pathway Inhibition, p53 Pathway<br>
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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:<br>
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Antioxidant Effects at Low Doses:<br>
-At lower concentrations, gallic acid is typically characterized by its ability to scavenge free radicals, thus reducing oxidative stress.<br>
This antioxidant property may help protect normal cells from DNA damage, reducing the risk of mutations that could lead to cancer.<br>
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Pro-oxidant Effects at High Doses: >50-100uM?<br>
-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.<br>
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Oral bioavailability is moderate 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.<br>
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<!-- Gallic Acid (GA) — Refined Time-Scale Flagged Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>ROS / Redox modulation (biphasic)</td>
<td>ROS ↑ at higher concentrations (reported); mitochondrial stress ↑</td>
<td>ROS ↓; antioxidant protection</td>
<td>P, R</td>
<td>Redox destabilization (tumor) / buffering (normal)</td>
<td>GA demonstrates dose-dependent redox behavior; pro-oxidant effects are most evident ≥50–100 µM in vitro.</td>
</tr>
<tr>
<td>2</td>
<td>Nrf2 / ARE antioxidant response</td>
<td>Context-dependent; may support stress adaptation</td>
<td>Nrf2 ↑; HO-1 ↑; GSH ↑</td>
<td>R, G</td>
<td>Redox regulation</td>
<td>Activation common in non-malignant oxidative stress models; tumor implications vary and may affect therapy sensitivity.</td>
</tr>
<tr>
<td>3</td>
<td>NF-κB inflammatory signaling</td>
<td>NF-κB ↓; COX-2, IL-6, TNF-α ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory + anti-survival transcription</td>
<td>One of the more consistent signaling findings across inflammatory and tumor models.</td>
</tr>
<tr>
<td>4</td>
<td>Intrinsic apoptosis (mitochondrial; p53-related)</td>
<td>ΔΨm ↓; Bax ↑; Bcl-2 ↓; caspases ↑; cyt-c ↑ (reported)</td>
<td>↔ (limited activation)</td>
<td>G</td>
<td>Cell death execution</td>
<td>Often ROS-mediated; p53 activation reported in several systems.</td>
</tr>
<tr>
<td>5</td>
<td>Cell-cycle checkpoints (G1 / G2-M)</td>
<td>Cell-cycle arrest ↑ (Cyclin/CDK modulation)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Phase varies by tumor model; commonly G1 or G2/M.</td>
</tr>
<tr>
<td>6</td>
<td>PI3K → AKT (± mTOR)</td>
<td>PI3K/AKT signaling ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival suppression</td>
<td>Likely secondary to redox and inflammatory signaling modulation.</td>
</tr>
<tr>
<td>7</td>
<td>MAPK pathways (ERK / JNK / p38)</td>
<td>JNK/p38 activation; ERK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Stress signaling reprogramming</td>
<td>Often linked to ROS-mediated apoptosis pathways.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>VEGF ↓ (reported in some models)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic modulation</td>
<td>Evidence present but less consistent than redox and NF-κB effects.</td>
</tr>
<tr>
<td>9</td>
<td>Invasion / metastasis (MMPs / EMT)</td>
<td>MMP2/MMP9 ↓; migration ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Likely downstream of NF-κB and MAPK modulation.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability constraint (phase II metabolism)</td>
<td>Rapid glucuronidation/sulfation; free GA low</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Plasma levels after dietary intake are generally below many in-vitro cytotoxic concentrations.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid redox interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute signaling and stress-response shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype outcomes)</li>
</ul>