Description: <b>Found</b> in dried fruit rind of Garcinia Indica with anti-inflammatory, antioxidant, anticancer, and antibacterial properties<br>
Garcinia Cambogia Extract.<br>
"We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol."<br>
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🔬1) NF-κB & AP-1 Suppression<br>
Garcinol inhibits NF-κB and AP-1 transcriptional activity in multiple cancer cell systems, reducing pro-inflammatory and pro-survival gene expression.<br>
📚 2) Epigenetic Regulation<br>
Garcinol is one of the few natural products shown to inhibit p300/CBP histone acetyltransferases, shifting chromatin acetylation and influencing gene expression (differentiation, apoptosis, EMT).
This is more specific than general “HDAC modulation.”<br>
💀 3) Apoptosis<br>
Studies report modulation of the Bcl-2 family and increased caspase activity, but this is often downstream of transcription/epigenetic changes, not a direct redox trigger.<br>
🧬 4) Cell Cycle & Proliferation<br>
Lower Cyclin D1, higher p21/p27, and G1/S arrest are common phenotypes.<br>
🧭 5) Invasion & Angiogenesis<br>
Garcinol reduces MMP-2/9 and angiogenic markers in multiple tumor cell assays.<br>
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<!-- Garcinol (Garc) — 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 / AP-1 signaling</td>
<td>NF-κB ↓; AP-1 ↓; downstream pro-survival/inflammatory outputs ↓</td>
<td>↔ or anti-inflammatory modulation in immune cells</td>
<td>R, G</td>
<td>Pro-survival & inflammatory transcription suppression</td>
<td>Garcinol is reported to inhibit NF-κB and AP-1 transcriptional activity, reducing inflammation and pro-growth signaling in multiple models.</td>
</tr>
<tr>
<td>2</td>
<td>Epigenetic regulation (HAT/HDAC modulation)</td>
<td>Inhibition of p300/CBP histone acetyltransferase; altered acetylation patterns</td>
<td>↔ baseline epigenetic state</td>
<td>R, G</td>
<td>Gene regulatory reprogramming</td>
<td>Garcinol directly inhibits histone acetyltransferases (especially p300/CBP), influencing chromatin state and gene expression linked to differentiation and proliferation.</td>
</tr>
<tr>
<td>3</td>
<td>Intrinsic apoptosis (mitochondrial / caspase-linked)</td>
<td>↑ Bax/Bak; ↓ Bcl-2/Bcl-xL; ↑ caspase-9/3</td>
<td>↔ minimal activation in normal cells</td>
<td>G</td>
<td>Execution of apoptosis</td>
<td>Often downstream of stress and survival pathway modulation; not as dominant as classic pro-oxidant molecules but consistent in many cell lines.</td>
</tr>
<tr>
<td>4</td>
<td>Cell-cycle checkpoints (p21/p27; Cyclin D1)</td>
<td>Cell-cycle arrest (often G1/S); Cyclin D1 ↓</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Frequently reported as later phenotypic outcome tied to reduced proliferation.</td>
</tr>
<tr>
<td>5</td>
<td>Invasion / metastasis programs (MMPs / EMT)</td>
<td>MMP-2/9 ↓; invasion/migration ↓; EMT markers ↓</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Linked mechanistically to NF-κB/AP-1 and epigenetic changes influencing MMP expression and EMT regulators.</td>
</tr>
<tr>
<td>6</td>
<td>Angiogenesis signaling (VEGF & pro-angiogenic factors)</td>
<td>VEGF ↓; pro-angiogenic markers ↓</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Sometimes measured in later in vivo or emulated assay systems; reflects downstream gene expression changes.</td>
</tr>
<tr>
<td>7</td>
<td>PI3K/AKT / survival kinases</td>
<td>↓ PI3K/AKT signaling (model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Survival/growth suppression</td>
<td>Modulation of survival kinases is reported in some systems but not a universal primary mechanism.</td>
</tr>
<tr>
<td>8</td>
<td>ROS / oxidative stress (context–dependent)</td>
<td>ROS modulation (inconsistent across models)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Conditional stress modulation</td>
<td>Some studies report mild ROS changes, but garcinol is not a strong pro-oxidant driver like BetA or curcumin in cancer cells.</td>
</tr>
<tr>
<td>9</td>
<td>Chemo-sensitization / combination relevance</td>
<td>Enhanced sensitivity to chemotherapeutics (context)</td>
<td>—</td>
<td>G</td>
<td>Combination leverage</td>
<td>Combination effects are reported in selected cell lines/model systems; not universal.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability constraint (oral exposure / formulation dependence)</td>
<td>Systemic exposure often limited without enhanced delivery</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Poor native bioavailability is common across polyphenols/bzp molecules; formulations improve systemic exposure.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (primary/physical-chemical effects; rapid signaling / kinase shifts)</li>
<li><b>R</b>: 30 min–3 hr (acute stress-response and transcription signaling)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)</li>
</ul>