Description: <b>Salvia officinalis</b>(common sage) has been studied for its potential therapeutic effects in Alzheimer's disease (AD) and cancer due to its antioxidant, anti-inflammatory, neuroprotective, and anticancer properties. <br>
<p><b>Salvia officinalis — AD relevance:</b> Sage has human clinical signals for cognition/AD, plausibly via <b>cholinesterase inhibition</b> plus anti-inflammatory/antioxidant support. Essential-oil chemotype matters for safety (thujone exposure).</p>
<p><b>Primary mechanisms (conceptual rank):</b><br>
1) ↑ Cholinergic tone (AChE/BChE inhibition; symptomatic cognitive support)AChE ↓ → ACh ↑ (symptomatic cognitive enhancement)<br>
2) ↓ Neuroinflammation (NF-κB/cytokine tone; model-supported)<br>
3) ↓ Oxidative stress (↓ ROS/lipid peroxidation; stress-defense support)<br>
4) Secondary network/synaptic efficiency effects (chronic adaptation)</p>
<p><b>Bioavailability / PK relevance:</b> Oral leaf extracts used in trials; effects are typically over weeks–months. Avoid equating leaf extract with essential oil dosing due to thujone-associated neurotoxicity risk.</p>
<p><b>Clinical evidence status:</b> Small double-blind RCT in mild–moderate AD (extract vs placebo) and additional placebo-controlled cognitive studies in non-AD populations; evidence is supportive but not definitive/disease-modifying.</p>
-Sage contains compounds (e.g., rosmarinic acid, luteolin, carnosic acid) that inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).This enhances acetylcholine levels, supporting memory and cognition — similar to drugs like donepezil.<br>
-High in phenolic compounds (e.g., flavonoids, diterpenes) that scavenge reactive oxygen species (ROS).<br>
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-High doses of thujone (a compound in some sage oils) may be neurotoxic or hepatotoxic.<br>
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<h3>Salvia officinalis — AD / Neurodegeneration Pathway Map</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th><th>Pathway / Axis</th><th>Cells</th><th>TSF</th><th>Primary Effect</th><th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>AChE ↓ → ACh ↑ (cholinergic synapse)</td>
<td>ACh ↑ (via AChE inhibition)</td>
<td>P/R</td>
<td>Improved synaptic cholinergic transmission</td>
<td>Extract inhibits acetylcholinesterase → reduced ACh breakdown → increased synaptic ACh. Symptomatic mechanism analogous to donepezil-class drugs.</td>
</tr>
<tr>
<td>2</td><td>Neuroinflammation (NF-κB / cytokines)</td>
<td>↓</td><td>R/G</td>
<td>Reduced inflammatory stress</td>
<td>Extracts show anti-inflammatory signaling in cell/biochemical models; relevance to AD progression is supportive.</td>
</tr>
<tr>
<td>3</td><td>ROS / lipid peroxidation</td>
<td>↓</td><td>P/R</td>
<td>Oxidative burden reduction</td>
<td>Phenolics/diterpenes contribute to antioxidant effects; typically requires sustained intake for tissue adaptation.</td>
</tr>
<tr>
<td>4</td><td>NRF2 antioxidant-response program</td>
<td>↔ / ↑ (context-dependent)</td><td>R/G</td>
<td>Stress-defense regulation</td>
<td>Consider as a supportive axis; not always directly measured in human cognition trials.</td>
</tr>
<tr>
<td>5</td><td>Ca²⁺ excitotoxicity interplay</td>
<td>↔</td><td>P/R</td>
<td>Not primary</td>
<td>More relevant to essential-oil neurotoxicity discussions than leaf-extract cognition trials; include only with explicit Ca²⁺ endpoints.</td>
</tr>
<tr>
<td>6</td><td>Aβ / tau-associated pathology</td>
<td>↔ (limited human evidence)</td><td>G</td>
<td>Not established clinically</td>
<td>Any anti-amyloid/tau claims are largely preclinical; avoid over-weighting without biomarker-confirmed replication.</td>
</tr>
<tr>
<td>7</td><td>Clinical Translation Constraint</td>
<td>↓ (constraint)</td><td>—</td>
<td>Safety + product variability</td>
<td>Essential oil/thujone can be pro-convulsant; regulators specify limits for thujone exposure in herbal products. Extract standardization and duration (weeks–months) matter.</td>
</tr>
</table>
<p><b>TSF legend:</b> P: 0–30 min; R: 30 min–3 hr; G: >3 hr</p>