Description: <p><b>Isovitexin</b> - Apigenin-6-C-Glucoside</p>
<p><b>Alternative Names:</b> Apigenin-6-C-glucoside, apigenin-6-C-β-D-glucopyranoside</p>
<p><b>Type:</b> Flavone C-glycoside / <b>apigenin derivative</b></p>
<p><b>Function:</b> Isovitexin is a naturally occurring C-glycosylated flavone and positional isomer of vitexin, with glucose attached to apigenin at the C-6 position. It exhibits antioxidant, anti-inflammatory, metabolic, neuroprotective, and antiproliferative activities and can influence NF-κB, Nrf2, MAPK, PI3K/AKT, AMPK, apoptotic, and oxidative-stress signaling.</p>
-similar to <a href="https://nestronics.ca/dbx/tbResList.php?qv=462">Vitexin</a><br>
<p><b>Isovitexin</b> — Isovitexin (IVT; ISV; IVX), also known as apigenin-6-C-glucoside or 6-C-β-D-glucopyranosylapigenin, is a naturally occurring C-glycosylated flavone and positional isomer of vitexin, in which glucose is attached to apigenin at carbon 6 rather than carbon 8. It occurs in food and medicinal plants including mung bean, rice, passionflower, and other botanical sources. It is formally classified as a flavone C-glycoside / apigenin derivative. Compared with vitexin, isovitexin has a smaller but distinct experimental literature and should be maintained as a separate compound. Anticancer activity remains preclinical.<br>
-buckwheat sprouts contain orientin, isoorientin, vitexin, isovitexin, and rutin</p>
<p><b>Primary mechanisms (ranked):</b></p>
<ol>
<li>Suppression of PI3K/AKT/mTOR survival signaling, associated with reduced proliferation, migration, invasion, EMT, and increased apoptosis.</li>
<li>Mitochondrial apoptosis through Bax induction, Bcl-2/Mcl-1 suppression, cytochrome-c release, caspase-3 activation, and PARP cleavage.</li>
<li>ER-stress-driven apoptosis and pro-death autophagy involving IRE1α/XBP1s, GRP78, CHOP, Beclin-1, ATG3/ATG5, and LC3-II.</li>
<li>Suppression of cancer stemness, including miR-34a induction and reduction of CD44, ABCG2, ALDH1, and NANOG.</li>
<li>Inhibition of EMT, migration, and invasion, substantially linked to PI3K/AKT/mTOR suppression in colorectal cancer models.</li>
<li>ROS/NRF2 modulation is strongly context-dependent: isovitexin generally decreases ROS and activates NRF2/HO-1 in nonmalignant oxidative-injury models; a generalized pro-oxidant anticancer mechanism has not been established for isovitexin.</li>
<li>Suppression of inflammatory MAPK/NF-κB signaling in nonmalignant inflammatory models.</li>
<li>CYP17A1 inhibition has recently been proposed in breast cancer, but current evidence is substantially less mature than the apoptosis and PI3K/AKT/mTOR evidence.</li>
</ol>
<p><b>Bioavailability / PK relevance:</b> Oral exposure is a significant translational limitation. C-glycosylation gives isovitexin greater chemical stability than many O-glycosides, but direct intestinal absorption is limited and substantial material reaches the intestine for microbial metabolism. Rat studies demonstrate absorption and broad tissue distribution after oral plant-extract administration, while intravenous isovitexin has a plasma half-life of approximately 1 hour and distributes particularly to kidney, intestine, and liver. Human isovitexin-specific PK data are not established.</p>
<p><b>In-vitro vs systemic exposure relevance:</b> Many mechanistic experiments use micromolar concentrations that may be difficult to reproduce as circulating unchanged isovitexin after ordinary dietary or oral exposure. Consequently, high-concentration cell-culture findings should not be interpreted as demonstrating clinically achievable anticancer activity. Intestinal exposure and metabolites may be more pharmacologically relevant after oral administration.</p>
<p><b>Clinical evidence status:</b> Preclinical. Anticancer evidence consists primarily of cell studies and rodent/xenograft experiments. No established human anticancer efficacy, randomized clinical trial evidence, or approved oncology indication was identified. Isovitexin has an FDA substance identifier but this does not constitute drug approval. Long-term human safety, therapeutic dosing, drug interactions, and cancer-specific pharmacokinetics remain insufficiently defined.</p>
<h3>Mechanistic Profile</h3>
<table>
<thead>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
</thead>
<tbody>
<tr>
<td>1</td>
<td>PI3K AKT mTOR survival signaling</td>
<td>↓ p-PI3K, ↓ p-AKT, ↓ p-mTOR</td>
<td>Context-dependent</td>
<td>↓ proliferation, ↓ survival, ↓ invasion, ↑ apoptosis</td>
<td>Strong direct evidence in colon cancer and also implicated in experimental AD. IGF-1 partially reverses anticancer effects, supporting pathway involvement.</td>
</tr>
<tr>
<td>2</td>
<td>Mitochondrial apoptosis</td>
<td>↑ Bax, ↑ cytochrome-c release, ↑ caspase-3, ↑ PARP cleavage, ↓ Bcl-2, ↓ Mcl-1</td>
<td>↓ apoptosis during oxidative injury</td>
<td>↑ cancer-cell apoptosis</td>
<td>Direction differs appropriately by cellular context: pro-apoptotic in malignant cells but cytoprotective in several nonmalignant injury models.</td>
</tr>
<tr>
<td>3</td>
<td>ER stress and unfolded protein response</td>
<td>↑ IRE1α, ↑ XBP1s, ↑ GRP78, ↑ CHOP</td>
<td>Not established</td>
<td>↑ apoptosis and autophagy</td>
<td>ER-stress inhibition substantially reverses isovitexin-induced apoptosis and autophagy in liver cancer cells, supporting a causal mechanism.</td>
</tr>
<tr>
<td>4</td>
<td>Autophagy</td>
<td>↑ Beclin-1, ↑ ATG3, ↑ ATG5, ↑ LC3-II</td>
<td>Context-dependent</td>
<td>↑ pro-death autophagy</td>
<td>In hepatoma models, autophagy facilitates rather than protects against isovitexin-induced apoptosis. Autophagy can be protective in neurological injury models.</td>
</tr>
<tr>
<td>5</td>
<td>Cancer stemness and miR-34a</td>
<td>↑ miR-34a, ↓ CD44, ↓ ABCG2, ↓ ALDH1, ↓ NANOG</td>
<td>Not established</td>
<td>↓ stemness and apoptosis resistance</td>
<td>Demonstrated in SK-Hep-1 hepatocellular carcinoma spheroids. miR-34a inhibition attenuates isovitexin activity.</td>
</tr>
<tr>
<td>6</td>
<td>EMT migration and invasion</td>
<td>↓ EMT, ↓ migration, ↓ invasion</td>
<td>Little cytotoxicity reported in normal colonic epithelial cells</td>
<td>↓ metastatic phenotype</td>
<td>Closely linked to PI3K/AKT/mTOR inhibition in colorectal cancer models.</td>
</tr>
<tr>
<td>7</td>
<td>ROS and oxidative stress</td>
<td>Context-dependent</td>
<td>↓ ROS, ↓ MDA, ↑ GSH, ↑ SOD</td>
<td>Antioxidant cytoprotection</td>
<td>Unlike isoorientin, a robust ROS↑ anticancer mechanism should not currently be assigned to isovitexin. Most direct isovitexin evidence supports ROS↓ in nonmalignant oxidative-stress models.</td>
</tr>
<tr>
<td>8</td>
<td>NRF2 HO-1 antioxidant response</td>
<td>Not established as a core anticancer mechanism</td>
<td>↑ NRF2, ↑ HO-1</td>
<td>↑ antioxidant defense</td>
<td>Secondary/contextual mechanism demonstrated in lung, liver, kidney, ageing, and oxidative-injury models.</td>
</tr>
<tr>
<td>9</td>
<td>NF-κB and MAPK inflammatory signaling</td>
<td>Context-dependent</td>
<td>↓ NF-κB, ↓ MAPK activation</td>
<td>↓ inflammatory signaling</td>
<td>Well supported in inflammatory injury models but substantially less established as a direct cancer-cell mechanism.</td>
</tr>
<tr>
<td>10</td>
<td>CYP17A1</td>
<td>↓ CYP17A1 activity</td>
<td>Not established</td>
<td>Potential ↓ steroidogenic growth signaling</td>
<td>Recent breast-cancer evidence combines computational target identification with experimental MCF-7 evaluation. Treat as emerging rather than core.</td>
</tr>
<tr>
<td>11</td>
<td>Clinical Translation Constraint</td>
<td>High experimental concentrations; no demonstrated therapeutic human exposure</td>
<td>Human systemic PK and long-term safety insufficiently characterized</td>
<td>Limits clinical extrapolation</td>
<td>Low gastrointestinal absorption, extensive intestinal disposition and metabolism, lack of cancer trials, and absence of validated clinical dosing are major constraints.</td>
</tr>
</tbody>
</table>
<br><br>
<p><b>Alzheimer's disease relevance:</b> Isovitexin has meaningful but entirely preclinical AD relevance. Direct evidence includes inhibition of AChE and BChE in biochemical assays, protection against Aβ-induced neuronal toxicity, and improvement of cognition, Aβ burden, neuroinflammation, and autophagic dysfunction in an STZ-induced mouse model. The latter study links benefit to miR-107-mediated suppression of PI3K/AKT/mTOR signaling. These findings justify retaining AD as a disease category, but they do not establish clinical efficacy.</p>
<p><b>Primary mechanisms (ranked):</b></p>
<ol>
<li>miR-107-mediated suppression of PI3K/AKT/mTOR and restoration of autophagic regulation.</li>
<li>Reduction of experimental Aβ burden and Aβ-associated neuronal toxicity.</li>
<li>Reduction of neuroinflammation, including TNF-α, IL-6, and caspase-1 signaling.</li>
<li>AChE and BChE inhibition in biochemical assays.</li>
<li>Antioxidant/neuroprotective activity and protection from excitotoxic injury.</li>
</ol>
<p><b>Clinical evidence status:</b> Preclinical only. No human Alzheimer's disease efficacy data or validated therapeutic dosing were identified.</p>
<h3>Alzheimer's Disease Mechanisms</h3>
<table>
<thead>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Modulation</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
</thead>
<tbody>
<tr>
<td>1</td>
<td>miR-107 PI3K AKT mTOR</td>
<td>↑ miR-107, ↓ PI3K/AKT/mTOR</td>
<td>Improved autophagic regulation and cognition</td>
<td>Mechanistically supported in an STZ-induced mouse AD model using antagomiR-107.</td>
</tr>
<tr>
<td>2</td>
<td>Amyloid beta pathology</td>
<td>↓ Aβ</td>
<td>↓ amyloid burden and toxicity</td>
<td>Reduced Aβ burden in the mouse AD model and protected PC12 cells from Aβ25-35 toxicity.</td>
</tr>
<tr>
<td>3</td>
<td>Autophagy</td>
<td>Normalization of LC3-II, ATG7 and Beclin-1</td>
<td>Improved proteostatic function</td>
<td>Direction is better represented as normalization rather than simply ↑ or ↓ because AD-associated autophagic dysfunction is model-dependent.</td>
</tr>
<tr>
<td>4</td>
<td>Neuroinflammation</td>
<td>↓ TNF-α, ↓ IL-6, ↓ caspase-1</td>
<td>↓ inflammatory neuronal injury</td>
<td>Demonstrated in the STZ mouse model.</td>
</tr>
<tr>
<td>5</td>
<td>Cholinesterases</td>
<td>↓ AChE, ↓ BChE</td>
<td>Potential preservation of cholinergic signaling</td>
<td>Direct biochemical inhibition; clinical relevance and achievable brain concentration are unknown.</td>
</tr>
<tr>
<td>6</td>
<td>Excitotoxic neuronal injury</td>
<td>↓ glutamate-induced neurotoxicity</td>
<td>↑ neuronal survival</td>
<td>Observed in mouse hippocampal slice experiments.</td>
</tr>
<tr>
<td>7</td>
<td>Clinical Translation Constraint</td>
<td>Human efficacy and CNS exposure not established</td>
<td>Limits AD translation</td>
<td>Oral bioavailability and human brain exposure are uncertain; all disease-specific evidence remains experimental.</td>
</tr>
</tbody>
</table>