Description: <a href="https://www.healthline.com/nutrition/astragalus"> <b>Astragalus</b></a> is an herb that has been used in traditional Chinese medicine for centuries.It has many purported health benefits, including immune-boosting, anti-aging and anti-inflammatory effects. <br>
Astragalus (AG; commonly referring to Astragalus membranaceus root; major constituents: astragaloside IV [AS-IV], polysaccharides [APS], flavonoids) is a traditional botanical immunomodulator. Its dominant biology is immune modulation and stress-adaptive signaling, ranking conceptually as: <br>
(1) immune activation/regulation (macrophage, NK, T-cell modulation), <br>
(2) NF-κB and inflammatory pathway tuning, <br>
(3) PI3K/Akt/mTOR and MAPK context-dependent signaling, and <br>
(4) NRF2-mediated cytoprotection/antioxidant effects. <br>
Bioavailability is variable and constituent-dependent; AS-IV has relatively low oral bioavailability, APS are high-molecular-weight and act largely via gut–immune interaction. Many in-vitro cancer studies use purified compounds at concentrations exceeding typical plasma levels. Clinical evidence exists primarily as adjunctive oncology support (quality-of-life, immune parameters); robust standalone anticancer efficacy is not established. Immune stimulation may enhance antitumor surveillance but effects are tumor- and context-dependent.<br>
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<h3>Astragalus (AG; Astragalus membranaceus) — Cancer-Relevant Pathway Effects</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells (↑/↓/↔ + qualifiers)</th>
<th>Normal Cells (↑/↓/↔ + qualifiers)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Immune Activation (NK / T cells / macrophages)</td>
<td>↑ immune-mediated cytotoxicity</td>
<td>↑ immune competence</td>
<td>G</td>
<td>Immunomodulation</td>
<td>APS enhances macrophage and NK activity; relevant as adjunct in oncology.</td>
</tr>
<tr>
<td>2</td>
<td>NF-κB Signaling</td>
<td>↓ NF-κB (tumor cells; context-dependent)</td>
<td>↔ / balanced activation</td>
<td>R–G</td>
<td>Inflammatory pathway tuning</td>
<td>May suppress tumor-promoting inflammation while supporting immune signaling.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K/Akt/mTOR</td>
<td>↓ Akt phosphorylation (model-dependent)</td>
<td>↔ / survival support</td>
<td>R–G</td>
<td>Anti-proliferative signaling</td>
<td>Reported in breast, lung, colorectal models; often purified AS-IV ≥10 µM.</td>
</tr>
<tr>
<td>4</td>
<td>MAPK (ERK/JNK/p38)</td>
<td>↓ ERK; ↑ JNK/p38 (stress-induced apoptosis; model-dependent)</td>
<td>↔ adaptive stress response</td>
<td>R</td>
<td>Apoptosis modulation</td>
<td>Context-specific activation of stress kinases.</td>
</tr>
<tr>
<td>5</td>
<td>ROS Modulation</td>
<td>↓ ROS (antioxidant; dose-dependent)</td>
<td>↓ ROS (protective)</td>
<td>P–R</td>
<td>Redox buffering</td>
<td>Flavonoid fraction contributes; may protect normal tissue during therapy.</td>
</tr>
<tr>
<td>6</td>
<td>NRF2 Axis</td>
<td>↑ NRF2 (context-dependent)</td>
<td>↑ NRF2 (cytoprotection)</td>
<td>R–G</td>
<td>Antioxidant gene induction</td>
<td>Potential chemo-protection risk in certain oxidative-therapy contexts.</td>
</tr>
<tr>
<td>7</td>
<td>Ca²⁺ Signaling</td>
<td>↔ / mild ↑ (model-dependent)</td>
<td>↔</td>
<td>—</td>
<td>Secondary</td>
<td>Not a dominant mechanistic axis.</td>
</tr>
<tr>
<td>8</td>
<td>Ferroptosis</td>
<td>↔ / potentially ↓ (antioxidant context)</td>
<td>↔</td>
<td>—</td>
<td>Secondary</td>
<td>Antioxidant nature may counter lipid peroxidation unless combined with pro-oxidant therapy.</td>
</tr>
<tr>
<td>9</td>
<td>Clinical Translation Constraint</td>
<td colspan="2">Constituent variability; low AS-IV bioavailability; adjunct evidence stronger than monotherapy data</td>
<td>—</td>
<td>Heterogeneity / PK</td>
<td>Used clinically as supportive therapy in some regions; lacks robust standalone RCT anticancer efficacy.</td>
</tr>
</table>
<div><b>TSF Legend:</b> P: 0–30 min R: 30 min–3 hr G: >3 hr</div>
<br>
<h3>Astragalus (AG) — Alzheimer’s Disease (AD)-Relevant Effects</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>AD Context (↑/↓/↔ + qualifiers)</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>Oxidative Stress (ROS)</td>
<td>↓ neuronal ROS</td>
<td>P–R</td>
<td>Neuroprotection</td>
<td>Flavonoids and saponins contribute antioxidant activity.</td>
</tr>
<tr>
<td>2</td>
<td>Neuroinflammation (NF-κB)</td>
<td>↓ microglial activation</td>
<td>R–G</td>
<td>Anti-inflammatory</td>
<td>Polysaccharides modulate cytokine signaling.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K/Akt Survival Pathway</td>
<td>↑ neuronal survival signaling</td>
<td>G</td>
<td>Neurotrophic support</td>
<td>Reported in ischemia and neurodegeneration models.</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial Function</td>
<td>↑ mitochondrial stability (model-dependent)</td>
<td>R–G</td>
<td>Energy metabolism support</td>
<td>Preclinical models suggest improved mitochondrial dynamics.</td>
</tr>
<tr>
<td>5</td>
<td>Clinical Translation Constraint</td>
<td>No robust AD RCT efficacy data</td>
<td>—</td>
<td>Evidence gap</td>
<td>Evidence primarily preclinical or small-scale adjunct trials.</td>
</tr>
</table>
<div><b>TSF Legend:</b> P: 0–30 min R: 30 min–3 hr G: >3 hr</div>