Description: <b>Caffeic acid</b> is a polyphenol antioxidant found in coffee, fruits, vegetables, and herbs. It may have anti-inflammatory, anticancer, anti-aging, and other health benefits.<br>
Caffeic acid (CA) is a dietary hydroxycinnamic acid found widely in plant foods and in coffee largely as chlorogenic acids (caffeoylquinic acids). CA is generally antioxidant / anti-inflammatory and is frequently reported to modulate Nrf2 and NF-κB signaling, with downstream effects on survival pathways (PI3K/AKT), MAPKs, cell cycle, and apoptosis in preclinical cancer models. A notable mechanistic nuance is a context-dependent pro-oxidant effect described in the presence of copper (Cu), where CA can drive oxidative DNA damage in vitro (often discussed as potentially relevant to tumors with higher copper levels).<br>
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-Caffeic acid phenethyl ester, the main representative component of propolis<br>
-Black chokeberry 141.14 mg/100 g F<br>
-Sunflower seed, meal 8.17 mg/100 g FW<br>
-Common sage, dried 26.40 mg/100 g FW<br>
-Ceylan cinnamon 24.20 mg/100 g FW<br>
-Nutmeg 16.30 mg/100 g FW<br>
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-Dual capacity of CA to act as an antioxidant during carcinogenesis and as a pro-oxidant against cancer cells, promoting their apoptosis or sensitizing them to chemotherapeutic drugs.<br>
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Pathways:<br>
-Caffeic acid is a potent antioxidant<br>
-Caffeic acid may also exhibit pro-oxidant behavior. At higher concentrations( 50–100 µM ?) or/and in the presence of transition metal ions (such as copper or iron), caffeic acid can participate in Fenton-like reactions, potentially leading to increased ROS generation.<br>
-Shown to inhibit NF-κB activation<br>
-Inhibitory effects on MAPK/ERK Pathway<br>
-PI3K/Akt Signaling Pathway<br>
-Activation of the Nrf2/ARE pathway <br>
-Cell cycle arrest at various checkpoints<br>
-Angiogenesis Inhibition<br>
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Caffeic acid typically shows low oral bioavailability (sometimes only a few percent of the ingested dose is systemically available) and a short plasma half-life (around 1–2 hours in animal models).<br>
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<!-- Caffeic Acid (CA) — Time-Scale Flagged Pathway Table (web-page ready) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB inflammatory transcription</td>
<td>NF-κB ↓; cytokines/COX-2/iNOS programs ↓ (reported)</td>
<td>Inflammation tone ↓ (common in injury models)</td>
<td>R, G</td>
<td>Anti-inflammatory / anti-survival transcription</td>
<td>CA is frequently reported to reduce NF-κB signaling in inflammatory and cancer models. Note: CAPE (the ester) is the “stronger” canonical NF-κB inhibitor; keep CA claims qualified as “reported.”</td>
</tr>
<tr>
<td>2</td>
<td>Nrf2/ARE antioxidant response (HO-1, GSH systems)</td>
<td>Stress adaptation modulation (context-dependent)</td>
<td>Nrf2 ↑; HO-1 ↑; antioxidant defenses ↑</td>
<td>R, G</td>
<td>Endogenous antioxidant upshift</td>
<td>CA can activate Nrf2/ARE programs in oxidative stress settings; tumor direction is model-dependent and should not be overstated as uniformly “good” or “bad.”</td>
</tr>
<tr>
<td>3</td>
<td>ROS / redox tone (antioxidant vs Cu-linked pro-oxidant)</td>
<td>ROS direction variable; pro-oxidant DNA damage reported with Cu (context)</td>
<td>Oxidative injury ↓ in many stress models</td>
<td>P, R, G</td>
<td>Redox modulation</td>
<td>CA is classically antioxidant, yet Cu-mediated pro-oxidant DNA breakage has been described in vitro; treat as conditional (metal availability, dose, cell type).</td>
</tr>
<tr>
<td>4</td>
<td>Intrinsic apoptosis (mitochondrial/caspase linked)</td>
<td>Apoptosis ↑; Bax ↑; caspases ↑ (reported)</td>
<td>↔ (generally less activation)</td>
<td>G</td>
<td>Cell death execution</td>
<td>Frequently observed downstream endpoint in tumor models, often coupled to NF-κB/PI3K/MAPK and stress/redox changes.</td>
</tr>
<tr>
<td>5</td>
<td>Cell-cycle control (Cyclins/CDKs; checkpoints)</td>
<td>Cell-cycle arrest ↑ (reported; phase varies)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often appears as later phenotype-level outcome after upstream signaling shifts.</td>
</tr>
<tr>
<td>6</td>
<td>PI3K → AKT (± mTOR) survival axis</td>
<td>PI3K/AKT ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Reported in multiple tumor systems; best kept as “reported/model-dependent,” not a primary direct target.</td>
</tr>
<tr>
<td>7</td>
<td>MAPK re-wiring (ERK / JNK / p38)</td>
<td>MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Stress/mitogenic signaling adjustment</td>
<td>Directions vary across models and doses; avoid fixed arrows without a specific cited study for your cancer type.</td>
</tr>
<tr>
<td>8</td>
<td>Invasion / metastasis programs (MMPs / EMT)</td>
<td>MMPs ↓; migration/invasion ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Often downstream of NF-κB/MAPK and inflammation changes; not universal across all cell lines.</td>
</tr>
<tr>
<td>9</td>
<td>Angiogenesis signaling (VEGF & related outputs)</td>
<td>VEGF / angiogenic outputs ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Later phenotype-level outcome; strength depends on model and exposure.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability / metabolism constraint (chlorogenic acids → conjugates)</td>
<td>Systemic exposure mostly as glucuronide/sulfate/methylated metabolites</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>After oral intake, CA/chlorogenic acids appear predominantly as conjugated metabolites; free CA levels are typically far below many in-vitro (µM) assay doses.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid redox/metal interactions; early signaling shifts)</li>
<li><b>R</b>: 30 min–3 hr (acute stress-response + transcription signaling changes)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype outcomes)</li>
</ul>