Description: <b>Ginkgo biloba</b> from an ancient tree.<br>
Ginkgo biloba leaf extracts (commonly standardized as EGb 761, ~24% flavonol glycosides and ~6% terpene lactones) are best known for antioxidant, anti-inflammatory, platelet-activating factor (PAF) antagonism, and neurovascular effects. In preclinical cancer models, Ginkgo constituents have been associated with modulation of NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, along with effects on cell cycle, apoptosis, and angiogenesis. Clinical oncology evidence is limited and heterogeneous. Important safety considerations include antiplatelet effects (bleeding risk) and CYP/P-gp interactions (product- and dose-dependent).<br>
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-Ginkgo can inhibit platelet aggregation <br>
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-Scavenges free radicals; reduces oxidative stress in neuronal cells
-Suppresses pro-inflammatory cytokines (e.g., TNF-α, IL-1β).<br>
-Enhances microcirculation and oxygen delivery to brain tissues.<br>
-Reduces Aβ plaque formation and associated neurotoxicity.<br>
-May improve memory, attention, and processing speed in early-stage AD.<br>
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<!-- Ginkgo biloba (EGb 761) — 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>Antioxidant systems (Nrf2/ARE; SOD, GSH)</td>
<td>Stress adaptation modulation (context-dependent)</td>
<td>Nrf2 ↑; antioxidant enzymes ↑; oxidative injury ↓</td>
<td>R, G</td>
<td>Redox buffering</td>
<td>Flavonol glycosides commonly activate antioxidant defenses; direction in tumors is model-dependent.</td>
</tr>
<tr>
<td>2</td>
<td>NF-κB inflammatory transcription</td>
<td>NF-κB ↓; cytokines/COX-2 ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory signaling</td>
<td>Preclinical studies report NF-κB modulation; strength varies by constituent and dose.</td>
</tr>
<tr>
<td>3</td>
<td>PAF receptor antagonism (ginkgolides)</td>
<td>Pro-tumor inflammatory signaling ↓ (context)</td>
<td>Platelet activation ↓; microcirculation effects</td>
<td>P, R</td>
<td>Lipid mediator antagonism</td>
<td>Ginkgolides are PAF antagonists; clinically relevant for antiplatelet/vascular effects.</td>
</tr>
<tr>
<td>4</td>
<td>PI3K → AKT (± mTOR) survival axis</td>
<td>PI3K/AKT modulation (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Observed in some tumor models; best described as reported/context-dependent.</td>
</tr>
<tr>
<td>5</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 by extract composition and cell type.</td>
</tr>
<tr>
<td>6</td>
<td>Cell-cycle control (Cyclins/CDKs)</td>
<td>Cell-cycle arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Reported in vitro; typically downstream of signaling changes.</td>
</tr>
<tr>
<td>7</td>
<td>Intrinsic apoptosis (mitochondrial/caspase linked)</td>
<td>Apoptosis ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cell death execution</td>
<td>Seen in selected cancer cell lines; not a universal cytotoxin signature.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (VEGF & related)</td>
<td>Angiogenic outputs ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic phenotype</td>
<td>Phenotype-level outcomes in some models; strength varies.</td>
</tr>
<tr>
<td>9</td>
<td>Drug metabolism / transport (CYPs, P-gp)</td>
<td>Potential interaction with chemo agents (context)</td>
<td>CYP/P-gp modulation (product- and dose-dependent)</td>
<td>R, G</td>
<td>Interaction constraint</td>
<td>Reports of CYP (e.g., CYP2C19/3A4) and P-gp modulation are mixed; interaction risk depends on extract and dose.</td>
</tr>
<tr>
<td>10</td>
<td>Safety constraint (antiplatelet / bleeding risk)</td>
<td>—</td>
<td>Platelet aggregation ↓; bleeding risk ↑ (context)</td>
<td>—</td>
<td>Clinical risk management</td>
<td>PAF antagonism and antiplatelet effects warrant caution with anticoagulants/antiplatelets and perioperatively.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid receptor/mediator interactions; early redox shifts)</li>
<li><b>R</b>: 30 min–3 hr (acute signaling and transcription changes)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype outcomes)</li>
</ul>
Ginkgo biloba — Alzheimer’s Disease (AD) Mechanism Table<br>
<!-- Ginkgo biloba (EGb 761) — Alzheimer's Disease Focused Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>AD / Neural Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Oxidative stress reduction (Nrf2/ARE; SOD, GSH)</td>
<td>Oxidative injury ↓; lipid peroxidation ↓</td>
<td>R, G</td>
<td>Neuroprotection via redox buffering</td>
<td>Flavonol glycosides enhance endogenous antioxidant defenses and reduce oxidative stress, a core driver in AD pathology.</td>
</tr>
<tr>
<td>2</td>
<td>Mitochondrial protection</td>
<td>ATP production stabilization; mitochondrial membrane integrity ↑</td>
<td>P, R</td>
<td>Energy support</td>
<td>EGb 761 has been reported to protect mitochondrial function and reduce ROS generation in neuronal models.</td>
</tr>
<tr>
<td>3</td>
<td>Neuroinflammation (NF-κB; microglial activation)</td>
<td>Microglial activation ↓; pro-inflammatory cytokines ↓</td>
<td>R, G</td>
<td>Anti-inflammatory neuroprotection</td>
<td>Reduction of neuroinflammatory signaling may contribute to slowed neurodegenerative processes.</td>
</tr>
<tr>
<td>4</td>
<td>Platelet-activating factor (PAF) antagonism</td>
<td>Improved cerebral microcirculation; reduced inflammatory mediator activity</td>
<td>P</td>
<td>Vascular support</td>
<td>Ginkgolides act as PAF antagonists; improved cerebral blood flow may support cognition in vascular/mixed dementia.</td>
</tr>
<tr>
<td>5</td>
<td>β-amyloid aggregation modulation</td>
<td>Aβ aggregation ↓ (reported in vitro)</td>
<td>G</td>
<td>Protein aggregation modulation</td>
<td>Preclinical studies suggest interference with Aβ toxicity and aggregation; clinical relevance remains uncertain.</td>
</tr>
<tr>
<td>6</td>
<td>Synaptic plasticity / neurotransmission</td>
<td>Cholinergic tone modulation (reported); synaptic resilience ↑</td>
<td>G</td>
<td>Cognitive support</td>
<td>Some evidence suggests improved synaptic function and neurotransmission in aging models.</td>
</tr>
<tr>
<td>7</td>
<td>Apoptosis suppression (neuronal survival)</td>
<td>Pro-apoptotic signaling ↓ (reported)</td>
<td>G</td>
<td>Neuronal preservation</td>
<td>Reduction of caspase activation and mitochondrial apoptotic signaling has been reported in neuronal injury models.</td>
</tr>
<tr>
<td>8</td>
<td>Clinical cognitive outcomes</td>
<td>Modest cognitive benefit in mild-to-moderate dementia (mixed results)</td>
<td>—</td>
<td>Symptom-level effect</td>
<td>Some randomized trials suggest small improvements in cognition or activities of daily living; others show limited effect. Benefit appears modest.</td>
</tr>
<tr>
<td>9</td>
<td>Safety constraint (antiplatelet effect)</td>
<td>Bleeding risk ↑ in susceptible patients</td>
<td>—</td>
<td>Clinical risk management</td>
<td>PAF antagonism and platelet aggregation inhibition require caution with anticoagulants and perioperative settings.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid receptor and mitochondrial interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute inflammatory and redox signaling shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)</li>
</ul>