Description: <b>Luteolin</b> a Flavonoid found in celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers.<br>
-MDR1 expression, MMP-9, IGF-1 and Epithelial to mesenchymal transition.<br>
<p><b>Luteolin</b> — a naturally occurring polyhydroxylated flavone (3′,4′,5,7-tetrahydroxyflavone) found in celery, parsley, peppers, broccoli and numerous medicinal plants. It is a dietary phytochemical and experimental small-molecule anticancer/anti-inflammatory agent rather than an approved anticancer drug. Standard abbreviation: LUT or Lut. Luteolin occurs as the free aglycone and as plant glycosides; after oral administration, circulating luteolin is dominated by glucuronide and sulfate conjugates rather than free aglycone. Its cancer pharmacology is pleiotropic and strongly model-dependent, with particularly recurrent effects on PI3K/AKT/mTOR, NF-κB, STAT3, redox regulation, mitochondrial apoptosis, EMT/invasion and cell-cycle control.</p>
<p><b>Primary mechanisms (ranked):</b></p>
<ol>
<li>PI3K/AKT/mTOR survival signaling suppression, reducing proliferation and facilitating apoptosis, autophagy or other programmed cell-death responses.</li>
<li>Redox-selective stress modulation: commonly ↑ ROS in susceptible cancer cells together with ↓ NRF2/HO-1/GSH-associated antioxidant defenses, while frequently reducing oxidative stress and activating protective antioxidant systems in normal tissues.</li>
<li>NF-κB and inflammatory survival signaling inhibition, with context-dependent suppression of TNF-α, IL-6, COX-2 and related inflammatory mediators.</li>
<li>Mitochondrial/intrinsic apoptosis activation through ↓ mitochondrial membrane potential, ↑ BAX:BCL-2 ratio, cytochrome-c release and caspase activation.</li>
<li>STAT3/JAK signaling suppression, reducing survival, stemness, inflammatory signaling and immune-evasion phenotypes in several tumor models.</li>
<li>EMT, migration and invasion suppression through modulation of E-cadherin, N-cadherin, vimentin, MMP2/MMP9, FAK, YAP/TAZ and related pathways.</li>
<li>Cell-cycle arrest through suppression of cyclins/CDKs and context-dependent induction of p21/p27 and p53 signaling.</li>
<li>Metabolic and hypoxic adaptation inhibition, including HIF-1α, PKM2, HK2 and glycolytic signaling in selected models.</li>
<li>Epigenetic modulation, including reported inhibition of DNMTs, HDAC-associated signaling and EZH2 in selected cancer models.</li>
<li>Additional context-dependent cell-death mechanisms including ER stress, autophagy, ferroptosis and pyroptosis.</li>
</ol>
<p><b>Bioavailability / PK relevance:</b> Oral luteolin has poor aqueous solubility and unfavorable systemic availability of unconjugated aglycone. It is absorbed from the intestine but undergoes extensive intestinal and hepatic glucuronidation and sulfation. Animal studies report low absolute bioavailability of free luteolin, commonly in the low-single-digit to low-tens percentage range depending on formulation and analytical definition. Nanoemulsions, lipid/phospholipid systems, cyclodextrins, nanoparticles and other delivery systems can substantially improve exposure experimentally. Luteolin and particularly some circulating conjugates can interact with OATP1B1/OATP2B1 transporters; in-vitro CYP inhibition has also been reported, making pharmacokinetic drug interactions plausible at sufficiently high exposure.</p>
<p><b>In-vitro vs systemic exposure relevance:</b> Many anticancer experiments use approximately 10–100 µM luteolin, often 20–50 µM or higher. These concentrations generally exceed sustained concentrations of free luteolin expected after conventional oral dietary or supplemental dosing because extensive conjugation limits circulating aglycone. Consequently, direct translation of many cell-culture IC50 values to standard oral supplementation is weak. Local gastrointestinal exposure, metabolites, tissue deconjugation and optimized formulations may partly alter this limitation.</p>
<p><b>Clinical evidence status:</b> Predominantly preclinical, but no longer exclusively preclinical. A 2025 single-arm phase I study administered luteolin 50 mg/day for six months to five men with localized prostate cancer undergoing active surveillance; no treatment-related adverse events were reported, but the study was far too small and uncontrolled to establish anticancer efficacy. A larger phase II single-arm multicenter Japanese study of 50 mg/day for one year is currently recruiting with a planned enrollment of 40 patients. Luteolin is therefore best categorized as early-human/phase I–II investigational evidence, not established cancer therapy. Preclinical evidence for chemotherapy and radiotherapy sensitization is substantial but remains cancer-, drug- and genotype-dependent.</p>
<br>
-Note <a href="tbResList.php?qv=118&tsv=1109&wNotes=on&exSp=open">half-life</a> 2–3 hours<br>
<a href="tbResList.php?qv=118&tsv=792&wNotes=on&exSp=open">BioAv </a> low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
<br>
Pathways:<br>
<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- induce
<a href="tbResList.php?qv=118&tsv=275&wNotes=on">ROS</a> production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.<br>
- ROS↑ related:
<a href="tbResList.php?qv=118&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?qv=118&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?qv=118&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?qv=118&tsv=356&wNotes=on">GRP78↑</a>,
<a href="tbResList.php?qv=118&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?qv=118&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?qv=118&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?qv=118&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?qv=118&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?qv=118&wNotes=on&word=HSP">HSP↓</a>
<br>
<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Lowers AntiOxidant defense in Cancer Cells:
<a href="tbResList.php?qv=118&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?qv=118&tsv=298&wNotes=on&word=SOD↓">SOD↓</a>,
<a href="tbResList.php?qv=118&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<a href="tbResList.php?qv=118&tsv=46&wNotes=on">Catalase↓</a>
<a href="tbResList.php?qv=118&tsv=597&wNotes=on">HO1↓</a>
<a href="tbResList.php?qv=118&wNotes=on&word=GPx">GPx↓</a>
<br>
- Raises
<a href="tbResList.php?qv=118&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?qv=118&tsv=275&wNotes=on&word=ROS↓">ROS↓</a>,
<a href="tbResList.php?qv=118&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?qv=118&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?qv=118&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?qv=118&tsv=46&wNotes=on&word=Catalase↑">Catalase↑</a>,
<br>
<!-- INFLAMMATION : NF-kB↓, COX2↓, COX2↓ PRO-INFL CYTOKINES: IL-1β↓, TNF-α↓, IL-6↓, IL-8↓, -->
- lowers
<a href="tbResList.php?qv=118&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?qv=118&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?qv=118&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?qv=118&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?qv=118&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?qv=118&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?qv=118&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<br>
<!-- GROWTH/METASTASES : EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1, uPA↓, VEGF↓, ERK↓
inhibiting metastasis-associated proteins such as ROCK1, FAK, (RhoA), NF-κB and u-PA, MMP-1 and MMP-13.-->
- inhibit Growth/Metastases :
<a href="tbResList.php?qv=118&tsv=604&wNotes=on">TumMeta↓</a>,
<a href="tbResList.php?qv=118&tsv=323&wNotes=on">TumCG↓</a>,
<a href="tbResList.php?qv=118&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=118&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?qv=118&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?qv=118&tsv=308&wNotes=on">TIMP2</a>,
<a href="tbResList.php?qv=118&tsv=415&wNotes=on">IGF-1↓</a>,
<a href="tbResList.php?qv=118&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=118&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?qv=118&tsv=273&wNotes=on">RhoA↓</a>,
<a href="tbResList.php?qv=118&tsv=214&wNotes=on">NF-κB↓</a>,
<a href="tbResList.php?qv=118&tsv=79&wNotes=on">CXCR4↓</a>,
<a href="tbResList.php?qv=118&tsv=105&wNotes=on">ERK↓</a>
<br>
<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=118&tsv=140&wNotes=on">HDAC↓</a>,
<a href="tbResList.php?qv=118&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=118&tsv=86&wNotes=on">DNMT3A↓</a>,
<a href="tbResList.php?qv=118&tsv=108&wNotes=on">EZH2↓</a>,
<a href="tbResList.php?qv=118&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?qv=118&wNotes=on&word=HSP">HSP↓</a>,
<br>
<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?qv=118&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?qv=118&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?qv=118&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?qv=118&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?qv=118&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?qv=118&tsv=895&wNotes=on">CDK6↓</a>,
<br>
<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?qv=118&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?qv=118&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?qv=118&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=118&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=118&tsv=1117&wNotes=on">TOP1↓</a>,
<a href="tbResList.php?qv=118&tsv=657&wNotes=on">TET1↓</a>,
<br>
<!-- GLYCOLYSIS : ATP↓, HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓, lactateProd, OXPHOS -->
- inhibits
<a href="tbResList.php?qv=118&tsv=129&wNotes=on">glycolysis</a>
and
<a href="tbResList.php?qv=118&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?qv=118&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?qv=118&tsv=772&wNotes=on">PKM2↓</a>,
<a href="tbResList.php?qv=118&tsv=35&wNotes=on">cMyc↓</a>,
<a href="tbResList.php?qv=118&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<a href="tbResList.php?qv=118&tsv=773&wNotes=on">HK2↓</a>,
<a href="tbResList.php?qv=118&tsv=356&wNotes=on">GRP78↑</a>,
<br>
<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=118&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=118&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=118&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?qv=118&wNotes=on&word=NOTCH">Notch↓</a>,
<a href="tbResList.php?qv=118&tsv=361&wNotes=on">PDGF↓</a>,
<a href="tbResList.php?qv=118&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<a href="tbResList.php?qv=118&&wNotes=on&word=ITG">Integrins↓</a>,
<br>
<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=118&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=118&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=118&wNotes=on&word=STAT">STAT↓</a>,
<a href="tbResList.php?qv=118&tsv=377&wNotes=on">Wnt↓</a>,
<a href="tbResList.php?qv=118&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=118&tsv=9&wNotes=on">AMPK</a>,
<a href="tbResList.php?qv=118&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=118&tsv=168&wNotes=on">JNK</a>,
<a href="tbResList.php?qv=118&word=Trx&wNotes=on">TrxR**</a>,
- Shown to modulate the nuclear translocation of
<a href="tbResList.php?qv=118&tsv=1132&wNotes=on&exSp=open&word=SREBP2">SREBP-2</a> (related to cholesterol).<br>
<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=118&tsv=1106&wNotes=on">chemo-sensitization</a>,
<a href="tbResList.php?qv=118&tsv=1171&wNotes=on">chemoProtective</a>,
<a href="tbResList.php?qv=118&tsv=1107&wNotes=on">RadioSensitizer</a>,
<a href="tbResList.php?qv=118&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=118&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=118&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=118&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=118&tsv=1188&wNotes=on">CardioProtective</a>,
<br>
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=118&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a><br>
<br>
-"Additionally, when reacted with concentrated sulfuric acid, a zinc salt is produced, resulting in a dark red and yellow solution. These color changes serve as a strong basis for the identification of luteolin"<br>
<br>
<h3>Common Dietary and Plant Sources of Luteolin</h3>
<table>
<thead>
<tr>
<th>Source</th>
<th>Luteolin Content</th>
<th>Approximate Equivalent</th>
<th>Relative Source Level</th>
<th>Notes</th>
</tr>
</thead>
<tbody>
<tr>
<td>Bird chili</td>
<td>1035 mg/kg</td>
<td>103.5 mg/100 g</td>
<td>Very high</td>
<td>Highest source in the cited quantitative food table; concentration may vary substantially by cultivar, maturity and analytical method.</td>
</tr>
<tr>
<td>Belimbi leaves</td>
<td>464.5 mg/kg</td>
<td>46.45 mg/100 g</td>
<td>Very high</td>
<td>Leaf material; not a common Western dietary source.</td>
</tr>
<tr>
<td>Onion leaves</td>
<td>391 mg/kg</td>
<td>39.1 mg/100 g</td>
<td>Very high</td>
<td>Green onion/scallion-type leaf tissue can contain substantially more luteolin than onion bulbs.</td>
</tr>
<tr>
<td>Belimbi fruit</td>
<td>202 mg/kg</td>
<td>20.2 mg/100 g</td>
<td>High</td>
<td>Tropical fruit source.</td>
</tr>
<tr>
<td>Dried asam gelugur</td>
<td>107.5 mg/kg</td>
<td>10.75 mg/100 g</td>
<td>High</td>
<td>Dried plant material; dry-weight concentration is not directly comparable with fresh vegetables.</td>
</tr>
<tr>
<td>Celery</td>
<td>80.5 mg/kg</td>
<td>8.05 mg/100 g</td>
<td>High</td>
<td>One of the most commonly cited dietary sources of luteolin; content differs among celery varieties and plant parts.</td>
</tr>
<tr>
<td>Broccoli</td>
<td>74.5 mg/kg</td>
<td>7.45 mg/100 g</td>
<td>High</td>
<td>Common dietary source. Other compositional surveys report a broad range, indicating strong cultivar and methodology effects.</td>
</tr>
<tr>
<td>Carrot</td>
<td>37.5 mg/kg</td>
<td>3.75 mg/100 g</td>
<td>Moderate</td>
<td>Common dietary source; luteolin may occur predominantly in glycosylated forms.</td>
</tr>
<tr>
<td>Green chili</td>
<td>33 mg/kg</td>
<td>3.3 mg/100 g</td>
<td>Moderate</td>
<td>Content varies substantially among Capsicum species and cultivars.</td>
</tr>
<tr>
<td>Limau purut leaves</td>
<td>30.5 mg/kg</td>
<td>3.05 mg/100 g</td>
<td>Moderate</td>
<td>Kaffir lime leaves; primarily used as a culinary herb rather than consumed in large quantities.</td>
</tr>
<tr>
<td>French bean</td>
<td>11 mg/kg</td>
<td>1.1 mg/100 g</td>
<td>Low to moderate</td>
<td>Common food source but substantially lower than celery, broccoli or onion leaves in the cited dataset.</td>
</tr>
<tr>
<td>White radish</td>
<td>9 mg/kg</td>
<td>0.9 mg/100 g</td>
<td>Low</td>
<td>Lower-luteolin dietary source in the cited dataset.</td>
</tr>
<tr>
<td>Parsley</td>
<td>Approximately 19.75 mg/100 g dried</td>
<td>Approximately 197.5 mg/kg dried</td>
<td>High</td>
<td>Frequently cited as a rich luteolin-containing herb. Dry-weight values should not be compared directly with fresh-weight vegetables.</td>
</tr>
<tr>
<td>Thyme</td>
<td>Approximately 51 mg/100 g</td>
<td>Approximately 510 mg/kg</td>
<td>Very high</td>
<td>Herb source reported in reviews; intake per serving is usually small despite the high concentration.</td>
</tr>
<tr>
<td>Peppermint</td>
<td>Approximately 11.33 mg/100 g fresh</td>
<td>Approximately 113.3 mg/kg</td>
<td>High</td>
<td>Fresh peppermint is a relatively concentrated herbal source.</td>
</tr>
<tr>
<td>Spinach</td>
<td>Approximately 1.11 mg/100 g</td>
<td>Approximately 11.1 mg/kg</td>
<td>Low to moderate</td>
<td>Common dietary source but lower than many herbs and celery-family plants.</td>
</tr>
<tr>
<td>Cabbage</td>
<td>Approximately 0.4–0.6 mg/100 g</td>
<td>Approximately 4–6 mg/kg</td>
<td>Low</td>
<td>Widely consumed but generally a relatively dilute luteolin source.</td>
</tr>
<tr>
<td>Black olives</td>
<td>Approximately 3.2–17.5 mg/100 g</td>
<td>Approximately 32–175 mg/kg</td>
<td>Moderate to high</td>
<td>Luteolin concentration depends strongly on olive cultivar and processing.</td>
</tr>
<tr>
<td>Green olives</td>
<td>Approximately 0.2–1.2 mg/100 g</td>
<td>Approximately 2–12 mg/kg</td>
<td>Low to moderate</td>
<td>Generally reported at lower concentrations than black olives.</td>
</tr>
<tr>
<td>Apple peel</td>
<td>Variable</td>
<td>Not consistently quantified</td>
<td>Low to moderate</td>
<td>Luteolin is reported principally in the peel rather than the flesh; concentration is cultivar-dependent.</td>
</tr>
<tr>
<td>Chrysanthemum flowers</td>
<td>Variable</td>
<td>Not consistently quantified</td>
<td>Potentially high</td>
<td>Traditional medicinal/tea source containing luteolin and luteolin glycosides.</td>
</tr>
</tbody>
</table>
<br><br>
<h3>Luteolin — Cancer Mechanisms</h3>
<table>
<thead>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
</thead>
<tbody>
<tr>
<td>1</td>
<td>PI3K / AKT / mTOR survival signaling</td>
<td>↓ PI3K; ↓ p-AKT; ↓ mTOR</td>
<td>↔ / adaptive modulation</td>
<td>R–G</td>
<td>↓ survival and proliferation; ↑ cell death</td>
<td>One of the most recurrent anticancer signaling effects; confirmed in multiple tumor systems and newer NSCLC studies.</td>
</tr>
<tr>
<td>2</td>
<td>ROS and antioxidant defense</td>
<td>↑ ROS; ↓ SOD/GSH/NRF2/HO-1 (context-dependent)</td>
<td>↓ ROS; ↑ antioxidant defenses (context-dependent)</td>
<td>P–R</td>
<td>Selective oxidative stress in susceptible tumors</td>
<td>Biphasic and highly context-dependent. ROS generation can be mechanistically upstream of NF-κB inhibition, JNK activation, apoptosis and radiosensitization.</td>
</tr>
<tr>
<td>3</td>
<td>NRF2 / HO-1 antioxidant survival axis</td>
<td>↓ NRF2; ↓ HO-1 (model-dependent)</td>
<td>↑ NRF2; ↑ HO-1 (model-dependent)</td>
<td>R–G</td>
<td>↓ tumor antioxidant capacity and drug resistance</td>
<td>Especially relevant in NRF2-high cancer cells. Luteolin has sensitized tumor cells to chemotherapy through NRF2 suppression, whereas NRF2 activation contributes to normal-tissue protection.</td>
</tr>
<tr>
<td>4</td>
<td>NF-κB inflammatory survival signaling</td>
<td>↓ NF-κB; ↓ inflammatory survival signaling</td>
<td>↓ pathological NF-κB activation</td>
<td>R–G</td>
<td>↑ apoptosis; ↓ inflammation and survival</td>
<td>ROS accumulation can participate upstream in some tumor models; not all NF-κB inhibition requires ROS.</td>
</tr>
<tr>
<td>5</td>
<td>Mitochondria and intrinsic apoptosis</td>
<td>↓ MMP; ↑ BAX; ↓ BCL-2; ↑ Cyt-c; ↑ caspase-9/3</td>
<td>↔ / ↓ mitochondrial injury under oxidative-stress conditions</td>
<td>R–G</td>
<td>↑ mitochondrial apoptosis</td>
<td>A common downstream execution mechanism following AKT inhibition, ROS elevation or ER stress.</td>
</tr>
<tr>
<td>6</td>
<td>JAK / STAT3 signaling</td>
<td>↓ STAT3; ↓ p-STAT3</td>
<td>↔ / ↓ inflammatory STAT3</td>
<td>R–G</td>
<td>↓ proliferation, stemness and immune escape</td>
<td>Recent work also links PRDX2 inhibition to JAK2/STAT3 suppression and ↓ PD-L1 in lung adenocarcinoma.</td>
</tr>
<tr>
<td>7</td>
<td>EMT and metastatic signaling</td>
<td>↓ EMT; ↑ E-cadherin; ↓ N-cadherin; ↓ vimentin; ↓ MMP2/9</td>
<td>↔</td>
<td>G</td>
<td>↓ migration, invasion and metastasis</td>
<td>PI3K/AKT, TGF-β/Smad, YAP/TAZ, FAK and related axes contribute depending on tumor type.</td>
</tr>
<tr>
<td>8</td>
<td>Cell-cycle control</td>
<td>↑ G1 or G2/M arrest; ↓ cyclins/CDKs; ↑ p21/p27</td>
<td>↔ (model-dependent)</td>
<td>G</td>
<td>↓ proliferation</td>
<td>Cell-cycle phase varies with tumor lineage and concentration.</td>
</tr>
<tr>
<td>9</td>
<td>p53 / JNK apoptotic signaling</td>
<td>↑ JNK; ↑ p53 stability/activity (context-dependent)</td>
<td>↔</td>
<td>R–G</td>
<td>↑ apoptosis and chemotherapy response</td>
<td>Cisplatin sensitization can depend strongly on functional p53.</td>
</tr>
<tr>
<td>10</td>
<td>Glycolysis and metabolic adaptation</td>
<td>↓ glycolysis; ↓ PKM2; ↓ HK2; ↓ ATP (model-dependent)</td>
<td>↔</td>
<td>G</td>
<td>↓ metabolic support for proliferation</td>
<td>Not universal across cancers; strongest evidence comes from selected hepatocellular and other metabolically dependent models.</td>
</tr>
<tr>
<td>11</td>
<td>HIF-1α and hypoxic adaptation</td>
<td>↓ HIF-1α; ↓ hypoxic adaptation</td>
<td>↔</td>
<td>G</td>
<td>↓ angiogenesis and hypoxia tolerance</td>
<td>Reported in breast, colon and other cancer models; linked to reduced VEGF signaling.</td>
</tr>
<tr>
<td>12</td>
<td>VEGF and angiogenesis</td>
<td>↓ VEGF; ↓ VEGFR signaling</td>
<td>↔ / anti-inflammatory vascular effects</td>
<td>G</td>
<td>↓ tumor angiogenesis</td>
<td>Predominantly preclinical evidence.</td>
</tr>
<tr>
<td>13</td>
<td>ER stress and unfolded protein response</td>
<td>↑ PERK/eIF2α/ATF4/CHOP; ↑ ER stress (model-dependent)</td>
<td>↓ pathological ER stress in several injury models</td>
<td>R–G</td>
<td>↑ tumor cell death</td>
<td>Illustrates luteolin's frequently opposite stress response in malignant versus nonmalignant models.</td>
</tr>
<tr>
<td>14</td>
<td>Autophagy</td>
<td>↑ Beclin-1; ↑ LC3-II; ↓ p62 (context-dependent)</td>
<td>↔ / protective modulation</td>
<td>G</td>
<td>Autophagic stress or contribution to cell death</td>
<td>Can be cytotoxic or cytoprotective depending on cancer model and treatment context.</td>
</tr>
<tr>
<td>15</td>
<td>GPX4-dependent ferroptosis</td>
<td>↓ GPX4; ↓ GSH; ↑ lipid oxidation; ↑ ferroptosis</td>
<td>↔ / ↓ ferroptotic injury in some normal-tissue models</td>
<td>R–G</td>
<td>↑ ferroptotic cancer-cell death</td>
<td>Recent colon-cancer work supports GPX4-linked ferroptosis plus enhanced antitumor immune activation.</td>
</tr>
<tr>
<td>16</td>
<td>Epigenetic regulation</td>
<td>↓ DNMT activity; ↓ HDAC-associated signaling; ↓ EZH2 (model-dependent)</td>
<td>↔ / context-dependent</td>
<td>G</td>
<td>Re-expression of growth-suppressive programs</td>
<td>Mechanistically interesting but less broadly established than AKT, redox and inflammatory pathways.</td>
</tr>
<tr>
<td>17</td>
<td>YAP / Wnt and tumor immunity</td>
<td>↓ YAP; ↓ Wnt-associated signaling; ↓ immune escape</td>
<td>↑ CTL functional activity indirectly</td>
<td>G</td>
<td>↑ antitumor T-cell effectiveness</td>
<td>2025 animal work suggests luteolin can enhance tumor-specific CTL therapy; clinical relevance remains unproven.</td>
</tr>
<tr>
<td>18</td>
<td>Chemosensitization</td>
<td>↑ response to cisplatin and several other agents (drug-dependent)</td>
<td>Variable; possible tissue protection in other contexts</td>
<td>G</td>
<td>↓ treatment resistance</td>
<td>Mechanisms include ↓ NRF2, ↓ AKT, ↑ p53/JNK, mitochondrial apoptosis and suppression of resistance pathways. Evidence remains predominantly preclinical.</td>
</tr>
<tr>
<td>19</td>
<td>Radiosensitization</td>
<td>↑ radiation-induced ROS and apoptosis</td>
<td>Potential radioprotection reported in nonmalignant models</td>
<td>R–G</td>
<td>↑ radiation response</td>
<td>In NSCLC models, p38/ROS/caspase signaling increased radiosensitivity; tumor versus normal-tissue effects require careful context separation.</td>
</tr>
<tr>
<td>20</td>
<td>Clinical Translation Constraint</td>
<td>High in-vitro concentrations often required</td>
<td>Systemic exposure dominated by conjugated metabolites</td>
<td>G</td>
<td>Limits translation of cell-culture potency</td>
<td>Poor aqueous solubility, extensive phase-II metabolism, formulation dependence, possible transporter/drug interactions and extremely limited controlled human oncology evidence remain major constraints.</td>
</tr>
</tbody>
</table>
<p>P: 0–30 min R: 30 min–3 hr G: >3 hr</p>
<br><br>
<p><b>Luteolin — Alzheimer’s disease relevance:</b> Luteolin has substantial preclinical neuroprotective evidence and is sufficiently relevant to Alzheimer’s disease to warrant a separate database section. Reported effects include ↓ amyloid-β production/accumulation, ↓ BACE1-associated amyloidogenic processing, ↓ tau hyperphosphorylation, ↓ neuroinflammation, ↓ oxidative stress, ↓ NLRP3/NF-κB signaling and ↑ BDNF/TrkB-associated neuroplasticity. Acetylcholinesterase inhibition has also been reported. However, evidence remains predominantly cellular and animal; convincing disease-modifying clinical evidence in Alzheimer’s disease is absent. Oral bioavailability and blood-brain exposure of free luteolin remain important translational constraints.</p>
<p><b>Clinical evidence status:</b> Preclinical. Contemporary reviews identify Alzheimer’s disease as the neurodegenerative disorder in which luteolin has been studied most extensively, but explicitly note that clinical therapeutic evidence remains deficient.</p>
<h3>Luteolin — 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>Neuroinflammation / NF-κB</td>
<td>↓ NF-κB; ↓ IL-1β; ↓ IL-6; ↓ TNF-α</td>
<td>↓ chronic neuroinflammation</td>
<td>Among the most consistently proposed neuroprotective actions.</td>
</tr>
<tr>
<td>2</td>
<td>Amyloid-β pathology</td>
<td>↓ Aβ; ↓ Aβ42</td>
<td>↓ amyloid burden</td>
<td>Supported predominantly by cellular and animal studies.</td>
</tr>
<tr>
<td>3</td>
<td>BACE1 / amyloidogenic processing</td>
<td>↓ BACE1</td>
<td>↓ amyloidogenic APP processing</td>
<td>Potential upstream mechanism contributing to reduced Aβ generation.</td>
</tr>
<tr>
<td>4</td>
<td>Tau phosphorylation</td>
<td>↓ p-tau</td>
<td>↓ tau pathology</td>
<td>Multiple preclinical models report reduced abnormal tau phosphorylation.</td>
</tr>
<tr>
<td>5</td>
<td>Oxidative stress / NRF2</td>
<td>↓ ROS; ↑ NRF2; ↑ antioxidant defenses</td>
<td>↓ neuronal oxidative injury</td>
<td>Direction differs from the pro-oxidant effect frequently exploited in cancer cells.</td>
</tr>
<tr>
<td>6</td>
<td>NLRP3 inflammasome</td>
<td>↓ NLRP3</td>
<td>↓ inflammasome-driven neuronal inflammation</td>
<td>Potential bridge between redox stress and neuroinflammation.</td>
</tr>
<tr>
<td>7</td>
<td>BDNF / TrkB neuroplasticity</td>
<td>↑ BDNF; ↑ TrkB</td>
<td>↑ synaptic and neuronal support</td>
<td>Observed in several neurobehavioral models.</td>
</tr>
<tr>
<td>8</td>
<td>Acetylcholinesterase</td>
<td>↓ AChE</td>
<td>↑ cholinergic signaling</td>
<td>Primarily biochemical/preclinical evidence; clinical magnitude is unknown.</td>
</tr>
<tr>
<td>9</td>
<td>Neuronal apoptosis and mitochondrial stress</td>
<td>↓ apoptosis; ↓ mitochondrial injury</td>
<td>↑ neuronal survival</td>
<td>Opposite phenotypic direction from luteolin-induced apoptosis in many cancer models.</td>
</tr>
<tr>
<td>10</td>
<td>Clinical Translation Constraint</td>
<td>Low free-luteolin exposure; limited human CNS data</td>
<td>Uncertain clinical efficacy</td>
<td>Human Alzheimer’s disease efficacy trials are insufficient; brain exposure and formulation remain unresolved.</td>
</tr>
</tbody>
</table>