Description: <b>Deguelin</b> is a natural compound of the flavonoid family of products isolated from several plant species, including Derris trifoliata Lour and Mundulea sericea (Leguminosae) (4)<br>
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Deguelin’s ability to modulate multiple signaling pathways—including PI3K/Akt, mTOR, NF-κB, HIF-1α, and MAPK<br>
While preclinical studies have utilized dosages in the approximate range of 4–8 mg/kg in animal models, these figures are specific to the experimental conditions and species used in those studies.<br>
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Deguelin is a rotenoid (isoflavonoid-like botanical insecticide class) found in some Lonchocarpus / Derris species. In cancer literature it’s most often described as a mitochondrial Complex I inhibitor with downstream energy stress + survival pathway suppression (Akt/PI3K, NF-κB) and apoptosis/autophagy induction. A major caution is neurotoxicity signal: rotenoids (including deguelin) have been used in Parkinson’s disease animal models via Complex I inhibition.<br>
-<p><b>Active identity:</b> Rotenoid (deguelin) — a potent mitochondrial Complex I inhibitor with downstream energy-stress signaling (AMPK/mTOR), survival pathway suppression (Akt, NF-κB), and apoptosis/autophagy induction in cancer models; higher caution category due to rotenoid neurotoxicity signals in animal models.</p>
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<!-- Deguelin (Deg) — Cancer-Oriented 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>Mitochondrial ETC Complex I inhibition (OXPHOS)</td>
<td>Complex I ↓; ATP ↓; energetic stress ↑ (reported)</td>
<td>Toxicity risk if exposure high/prolonged (mitochondrial inhibition)</td>
<td>P, R</td>
<td>Bioenergetic choke-point</td>
<td>Deguelin is a rotenoid-class Complex I inhibitor; downstream effects often reflect energy stress + ROS/redox destabilization.</td>
</tr>
<tr>
<td>2</td>
<td>PI3K → AKT survival axis</td>
<td>Akt signaling ↓ (reported; chemoprevention & tumor models)</td>
<td>↔</td>
<td>R, G</td>
<td>Survival/growth suppression</td>
<td>Deguelin is widely described as an Akt-pathway suppressor in cancer/chemoprevention literature.</td>
</tr>
<tr>
<td>3</td>
<td>AMPK → mTOR → survivin axis</td>
<td>AMPK ↑; mTOR ↓; survivin ↓ (reported)</td>
<td>↔</td>
<td>R, G</td>
<td>Energy-stress signaling → anti-growth</td>
<td>Frequently presented as a mechanistic bridge between mitochondrial inhibition and reduced survival/proliferation programs.</td>
</tr>
<tr>
<td>4</td>
<td>NF-κB inflammatory / survival transcription</td>
<td>IKK/IκB/NF-κB activity ↓ (reported)</td>
<td>Inflammation tone ↓ (context)</td>
<td>R, G</td>
<td>Anti-inflammatory + anti-survival transcription</td>
<td>Deguelin has been reported to suppress NF-κB signaling in multiple tumor systems.</td>
</tr>
<tr>
<td>5</td>
<td>Hsp90 client disruption (Akt, survivin, CDK4) (reported)</td>
<td>Hsp90 client stability ↓; Akt/survivin/CDK4 ↓ (reported)</td>
<td>↔</td>
<td>R, G</td>
<td>Multi-node pathway destabilization</td>
<td>Some models report deguelin disrupts Hsp90-client interactions contributing to survival/proliferation collapse.</td>
</tr>
<tr>
<td>6</td>
<td>Intrinsic apoptosis (mitochondrial)</td>
<td>ΔΨm ↓; cytochrome-c ↑; caspases ↑; cl-PARP ↑ (reported)</td>
<td>↔ / toxicity risk at higher exposure</td>
<td>G</td>
<td>Cell death execution</td>
<td>Often downstream of energetic stress + survival pathway suppression.</td>
</tr>
<tr>
<td>7</td>
<td>Autophagy modulation</td>
<td>Autophagy ↑ (reported; context-dependent; can be pro-death or adaptive)</td>
<td>↔</td>
<td>G</td>
<td>Stress response / cell fate shift</td>
<td>Autophagy is frequently reported alongside apoptosis; directionality and functional role vary by model.</td>
</tr>
<tr>
<td>8</td>
<td>Cell-cycle control</td>
<td>Arrest ↑ (reported); cyclins/CDKs ↓ (context)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often explained as downstream of Akt/mTOR and Hsp90-client disruption effects.</td>
</tr>
<tr>
<td>9</td>
<td>Angiogenesis / hypoxia programs (HIF-1α, VEGF) (reported)</td>
<td>HIF-1α/VEGF outputs ↓ (reported in some models)</td>
<td>↔</td>
<td>R, G</td>
<td>Anti-angiogenic support</td>
<td>Anti-angiogenic effects are reported but are less “core” than the mitochondrial/Akt axes.</td>
</tr>
<tr>
<td>10</td>
<td>Safety constraint: rotenoid neurotoxicity signal</td>
<td>—</td>
<td>Parkinsonism-like syndrome reported in rat model with deguelin exposure</td>
<td>—</td>
<td>Translation constraint</td>
<td>Deguelin (like rotenone) is a potent Complex I inhibitor; neurotoxicity signals exist in animal PD models, so long-term/high exposure should be treated as higher-risk than typical polyphenols.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (bioenergetic inhibition begins; early redox/kinase shifts)</li>
<li><b>R</b>: 30 min–3 hr (AMPK/mTOR/NF-κB and stress pathway rewiring)</li>
<li><b>G</b>: >3 hr (cell-cycle arrest, apoptosis/autophagy outcomes)</li>
</ul>