Description: <b>Rutin</b>, a Quercetin Glycoside<br>
Rutin, a natural flavonoid glycoside found in many plants like buckwheat, citrus fruits, and apples, has shown promising neuroprotective and anticancer properties.<br>
Rutin is a flavonoid glycoside composed of quercetin bound to the disaccharide rutinose. It is widely found in buckwheat, citrus fruits, apples, and tea. In cancer models, rutin exhibits antioxidant, anti-inflammatory, anti-proliferative, and pro-apoptotic effects. Because it is glycosylated, rutin itself has relatively low cellular permeability; many biological effects are mediated after intestinal hydrolysis to quercetin and subsequent phase-II metabolites. Mechanistically, rutin is most consistently associated with suppression of NF-κB and PI3K/AKT signaling, modulation of MAPK pathways, redox regulation (Nrf2/ROS balance), inhibition of angiogenesis (VEGF), and induction of cell-cycle arrest and apoptosis in preclinical systems. Effects are model-dependent and often concentration-dependent, with antioxidant behavior dominating in normal tissue contexts and context-dependent pro-oxidant effects described in some tumor settings.<br>
-Scavenges free radicals, reduces oxidative stress<br>
-Inhibits pro-inflammatory cytokines like IL-1β, TNF-α, and reduces activation of NF-κB.<br>
-Inhibition of Aβ Aggregation (AD)<br>
-Mild inhibitory effects on acetylcholinesterase (AChE), helping enhance cholinergic function.<br>
-May upregulate BDNF expression<br>
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Cancer:<br>
-Induces cell cycle arrest in G2/M phase.<br>
-Inhibits VEGF, Suppresses MMP-2 and MMP-9<br>
-Inhibits PI3K/Akt/mTOR, MAPK, and NF-κB signaling pathways.<br>
-Enhances sensitivity to Chemotherapy drugs like doxorubicin and cisplatin<br>
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Rutin has poor oral bioavailability, but this can be improved with nanoformulations or co-administration with absorption enhancers like piperine or quercetin.<br>
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<h3> Cancer Pathway Table: Rutin</h3>
<!-- Cancer Pathway Table: Rutin -->
<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>NF-κB inflammatory / survival signaling</td>
<td>NF-κB ↓; COX-2, cytokines ↓ (reported)</td>
<td>Inflammatory tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory / anti-survival</td>
<td>Frequently reported mechanism; contributes to reduced tumor-promoting inflammation and survival signaling.</td>
</tr>
<tr>
<td>2</td>
<td>PI3K → AKT → mTOR axis</td>
<td>PI3K/AKT ↓; proliferation ↓ (model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth signaling suppression</td>
<td>Observed in several tumor models; often secondary to upstream redox and inflammatory modulation.</td>
</tr>
<tr>
<td>3</td>
<td>Cell-cycle regulation (Cyclins/CDKs; G1 or G2/M arrest)</td>
<td>Cell-cycle arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Associated with reduced Cyclin D1/CDK expression; typically downstream of survival pathway inhibition.</td>
</tr>
<tr>
<td>4</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>Bax ↑; Bcl-2 ↓; caspases ↑ (reported)</td>
<td>Minimal activation at lower exposure</td>
<td>G</td>
<td>Apoptotic execution</td>
<td>Apoptosis induction frequently reported in vitro; magnitude depends on achievable intracellular concentration.</td>
</tr>
<tr>
<td>5</td>
<td>ROS modulation (biphasic redox behavior)</td>
<td>ROS ↑ in some tumor contexts; apoptosis ↑</td>
<td>ROS ↓ (antioxidant protection)</td>
<td>P, R</td>
<td>Redox modulation</td>
<td>Rutin is classically antioxidant but may promote oxidative stress in tumor cells under certain conditions (dose/metal-dependent).</td>
</tr>
<tr>
<td>6</td>
<td>Nrf2 / ARE antioxidant response</td>
<td>Context-dependent modulation</td>
<td>Nrf2 ↑; antioxidant enzymes ↑</td>
<td>R, G</td>
<td>Redox buffering</td>
<td>Common polyphenol signature; may protect normal tissue from oxidative injury.</td>
</tr>
<tr>
<td>7</td>
<td>MAPK pathways (ERK / JNK / p38)</td>
<td>Stress-MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>JNK/p38 activation reported in apoptosis contexts; ERK modulation varies by model.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>VEGF ↓; angiogenic outputs ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Often secondary to NF-κB and PI3K suppression.</td>
</tr>
<tr>
<td>9</td>
<td>Invasion / metastasis (MMPs / EMT)</td>
<td>MMP2/MMP9 ↓; migration ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Typically downstream of inflammatory and MAPK modulation.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability constraint (glycoside → quercetin metabolism)</td>
<td>Systemic exposure mainly as metabolites</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Rutin has limited direct cellular uptake; many effects likely mediated after conversion to quercetin and phase-II metabolites.</td>
</tr>
</table>
<p><small>
TSF: P = 0–30 min (rapid redox interactions), R = 30 min–3 hr (acute signaling shifts), G = >3 hr (gene-regulatory adaptation and phenotype outcomes).
</small></p>
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<p>
<h3>Alzheimer’s Disease (AD) Summary — Rutin</h3>
Rutin has been studied in preclinical neurodegeneration models for its antioxidant, anti-inflammatory, and mitochondrial-protective properties. It is reported to modulate Nrf2 signaling, suppress NF-κB–mediated neuroinflammation, reduce oxidative stress, and attenuate amyloid-β–induced neuronal injury in experimental systems. Many effects may be mediated after hydrolysis to quercetin. Human clinical evidence remains limited.
</p>
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<h3> Alzheimer’s Disease Table: Rutin</h3>
<!-- Alzheimer’s Disease Table: Rutin -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>AD / Neurodegeneration Context</th>
<th>Normal Brain Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Nrf2 / ARE antioxidant response</td>
<td>Nrf2 ↑; HO-1 ↑; GSH ↑; oxidative damage ↓ (reported)</td>
<td>Redox homeostasis support</td>
<td>R, G</td>
<td>Antioxidant neuroprotection</td>
<td>Consistent polyphenol signature; reduces lipid peroxidation and ROS markers in AD models.</td>
</tr>
<tr>
<td>2</td>
<td>NF-κB / neuroinflammation</td>
<td>Microglial activation ↓; TNF-α / IL-1β ↓ (reported)</td>
<td>Inflammatory tone moderation</td>
<td>R, G</td>
<td>Anti-inflammatory modulation</td>
<td>Neuroinflammation is a core AD driver; rutin shows suppression in animal models.</td>
</tr>
<tr>
<td>3</td>
<td>Amyloid-β toxicity modulation</td>
<td>Aβ-induced ROS ↓; neuronal apoptosis ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-amyloid support</td>
<td>Evidence mainly from in vitro and rodent models; not confirmed clinically.</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial protection</td>
<td>ΔΨm stabilization; ATP preservation (reported)</td>
<td>Mitochondrial resilience</td>
<td>R</td>
<td>Bioenergetic protection</td>
<td>Opposes mitochondrial dysfunction induced by oxidative stress.</td>
</tr>
<tr>
<td>5</td>
<td>MAPK (JNK / p38 stress signaling)</td>
<td>Stress-MAPK suppression (reported)</td>
<td>↔</td>
<td>P, R</td>
<td>Stress signaling reduction</td>
<td>JNK/p38 activation linked to neuronal apoptosis; suppression reported in models.</td>
</tr>
<tr>
<td>6</td>
<td>Cholinergic signaling (reported in some models)</td>
<td>AChE activity ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cognitive support (model-based)</td>
<td>Evidence limited; magnitude smaller than pharmaceutical AChE inhibitors.</td>
</tr>
<tr>
<td>7</td>
<td>BBB penetration (metabolite-driven)</td>
<td>Effects likely via quercetin metabolites</td>
<td>Systemic metabolism required</td>
<td>—</td>
<td>Translation constraint</td>
<td>Parent rutin has limited direct brain penetration; hydrolysis/metabolism important.</td>
</tr>
<tr>
<td>8</td>
<td>Clinical evidence</td>
<td>Limited human AD trials</td>
<td>—</td>
<td>—</td>
<td>Evidence constraint</td>
<td>Most data preclinical; not established as AD therapy.</td>
</tr>
</table>
<p><small>
TSF: P = 0–30 min (early signaling modulation), R = 30 min–3 hr (stress-response shifts), G = >3 hr (gene-regulatory and neuroprotective outcomes).
</small></p>