Description: <b>Perilla</b> (commonly Perilla frutescens) is an herb used traditionally in various Asian cuisines and traditional medicine. It contains several bioactive compounds including flavonoids, phenolic acids, and fatty acids, which have been studied for their antioxidant, anti-inflammatory, and antimicrobial properties.</br>
Perilla (Perilla frutescens) is an herb used as food and traditional medicine. Mechanistically it’s best treated as a polyphenol-rich extract, often characterized by rosmarinic acid (plus luteolin/apigenin-class flavonoids depending on preparation). In cancer models, perilla extracts and rosmarinic acid–rich fractions are most consistently associated with anti-inflammatory signaling (NF-κB↓), Nrf2/antioxidant activation in normal tissues, and downstream cell-cycle/apoptosis modulation that is generally moderate and model-dependent.<br>
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<p><b>Active fractions (context-dependent):</b> Rosmarinic acid–rich polyphenols (often dominant), plus flavones/flavonoids (luteolin/apigenin-class depending on extract). Effects vary strongly by preparation (leaf vs seed; aqueous vs ethanol; standardized vs crude).</p>
<!-- Perilla (PER) — Cancer-Oriented 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>NF-κB inflammatory signaling</td>
<td>NF-κB ↓; COX-2, IL-6, TNF-α ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory / anti-survival modulation</td>
<td>Most consistent mechanistic theme for perilla and rosmarinic-acid–rich fractions.</td>
</tr>
<tr>
<td>2</td>
<td>Nrf2 / ARE antioxidant response</td>
<td>Context-dependent modulation</td>
<td>Nrf2 ↑; HO-1 ↑; GSH systems ↑</td>
<td>R, G</td>
<td>Redox buffering</td>
<td>Common polyphenol signature; tumor implications vary and may affect therapy sensitivity in some contexts.</td>
</tr>
<tr>
<td>3</td>
<td>ROS / redox modulation</td>
<td>ROS ↓ (often) or variable; pro-oxidant effects not dominant</td>
<td>Oxidative stress ↓ (protective)</td>
<td>P, R</td>
<td>Antioxidant-leaning redox modulation</td>
<td>Perilla is typically antioxidant in inflammatory/oxidative injury models; tumor cytotoxicity is usually weaker than strong pro-oxidants.</td>
</tr>
<tr>
<td>4</td>
<td>MAPK pathways (ERK / JNK / p38)</td>
<td>MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>Direction varies with extract composition and cell line; often downstream of redox/inflammation shifts.</td>
</tr>
<tr>
<td>5</td>
<td>PI3K → AKT (± mTOR)</td>
<td>PI3K/AKT ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Often secondary to NF-κB and oxidative stress pathway changes.</td>
</tr>
<tr>
<td>6</td>
<td>Cell-cycle arrest (G1 / G2-M)</td>
<td>Cell-cycle arrest ↑ (reported; modest)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Phenotype-level effect; strength depends on dose and extract standardization.</td>
</tr>
<tr>
<td>7</td>
<td>Intrinsic apoptosis (mitochondrial)</td>
<td>Apoptosis ↑ (reported; modest); caspases ↑</td>
<td>↔ (limited activation)</td>
<td>G</td>
<td>Conditional cytotoxicity</td>
<td>Usually not a “direct toxin” signature; more consistent as an anti-inflammatory/antioxidant modulator.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>VEGF ↓ (reported in some systems)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic modulation</td>
<td>Evidence exists but is less consistent than NF-κB/Nrf2 effects.</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>Often downstream of NF-κB and MAPK modulation; not universal across models.</td>
</tr>
<tr>
<td>10</td>
<td>Extract variability / bioavailability constraint</td>
<td>Activity varies by part (leaf/seed), solvent, and standardization</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Perilla is best treated as “rosmarinic-rich polyphenol extract”; systemic exposure may not match in-vitro doses.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid redox interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute transcription/signaling shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory and phenotype-level outcomes)</li>
</ul>