Description: <b>Polyphenol</b> of many herbs - rosemary, perilla, sage mint and basil. Rosmarinic acid (RA) is predominantly found in a variety of medicinal and culinary herbs, especially those belonging to the Lamiaceae family, including rosemary (Rosmarinus officinalis), basil (Ocimum basilicum), sage (Salvia officinalis), thyme (Thymus vulgaris), and mints (Mentha spp.). In addition to the Lamiaceae family, RA is also present in plants from other families, such as Boraginaceae and Apiaceae.<br>
-Rosmarinic acid is one of the hydroxycinnamic acids, and was initially isolated and purified from the extract of rosemary, a member of mint family (Lamiaceae)<br>
-Its chemical structure allows it to act as a free radical scavenger by donating hydrogen atoms to stabilize ROS and free radicals. <br>
RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals, thus interrupting oxidative chain reactions.
It can modulate the activity of enzymes involved in OS, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), underscoring its potential role in preventing oxidative damage at the cellular level.<br>
-divided as rosemary extract, carnosic acid, rosmarinic acid?<br>
<br>
Summary:<br>
-Capacity to chelate transition metal ions, particularly
<a href="tbResList.php?qv=142&tsv=835&wNotes=on">ironChelator</a> (Fe2+)
and copper (Cu2+)<br>
-RA plus Cu(II)-induced oxidative DNA damage, which causes ROS<br>
-rosmarinic acid (RA) as a potential inhibitor of
<a href="tbResList.php?qv=142&tsv=1178&wNotes=on">MARK4↓</a> (inhibiting to tumor growth, invasion, and metastasis) activity (IC50 = 6.204 µM)<br>
<br>
-Note <a href="tbResList.php?qv=142&tsv=1109&wNotes=on&exSp=open">half-life</a> 1.5–2 hours.<br>
<a href="tbResList.php?qv=142&tsv=792&wNotes=on&exSp=open">BioAv</a> water-soluble, rapid absorbtion
<br>
Pathways:<br>
<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- varying results of
<a href="tbResList.php?qv=142&tsv=275&wNotes=on">ROS</a> up or down in cancer cells.
Plus a
<a href="https://nestronics.ca/dbx/tbResEdit.php?rid=3017">report</a>
of lowering ROS and no effect on Tumor cell viability.<br>
However always seems to lower
<a href="tbResList.php?qv=142&tsv=275&wNotes=on&word=ROS↓">ROS↓</a> in normal cells.<br>
- ROS↑ related:
<a href="tbResList.php?qv=142&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?qv=142&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?qv=142&tsv=459&wNotes=on">UPR↑</a>,
<!-- <a href="tbResList.php?qv=142&tsv=356&wNotes=on">GRP78↑</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>, -->
<a href="tbResList.php?qv=142&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?qv=142&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?qv=142&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?qv=142&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?qv=142&wNotes=on&word=HSP">HSP↓</a>,
<!--<a href="tbResList.php?qv=142&wNotes=on&word=Prx">Prx</a>, mitochondrial antioxidant enzyme-->
<br>
<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- No indication of Lowering AntiOxidant defense in Cancer Cells:
<!--<a href="tbResList.php?qv=142&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?qv=142&word=Trx&wNotes=on">TrxR↓**</a>,
<a href="tbResList.php?qv=142&tsv=298&wNotes=on&word=SOD↓">SOD↓</a>,
<a href="tbResList.php?qv=142&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<a href="tbResList.php?qv=142&tsv=46&wNotes=on">Catalase↓</a>
<a href="tbResList.php?qv=142&tsv=597&wNotes=on">HO1↓</a>
<a href="tbResList.php?qv=142&wNotes=on&word=GPx">GPx↓</a>
-->
<br>
- Raises
<a href="tbResList.php?qv=142&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:(and perhaps even in cancer cells)
<a href="tbResList.php?qv=142&tsv=275&wNotes=on&word=ROS↓">ROS↓</a>,
<a href="tbResList.php?qv=142&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>***,
<a href="tbResList.php?qv=142&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?qv=142&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?qv=142&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=142&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?qv=142&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?qv=142&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?qv=142&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?qv=142&tsv=908&wNotes=on&word=NLRP3↓">NLRP3↓</a>,
<a href="tbResList.php?qv=142&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?qv=142&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?qv=142&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?qv=142&tsv=368&wNotes=on&word=IL8↓">IL-8↓</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=142&tsv=604&wNotes=on">TumMeta↓</a>,
<a href="tbResList.php?qv=142&tsv=323&wNotes=on">TumCG↓</a>,
<a href="tbResList.php?qv=142&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?qv=142&tsv=204&wNotes=on">MMPs↓</a>,
<a href="tbResList.php?qv=142&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?qv=142&tsv=203&wNotes=on">MMP9↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=308&wNotes=on">TIMP2</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=415&wNotes=on">IGF-1↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=428&wNotes=on">uPA↓</a>, -->
<a href="tbResList.php?qv=142&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=142&tsv=1284&wNotes=on">ROCK1↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=110&wNotes=on">FAK↓</a>, -->
<a href="tbResList.php?qv=142&tsv=273&wNotes=on">RhoA↓</a>,
<a href="tbResList.php?qv=142&tsv=214&wNotes=on">NF-κB↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=79&wNotes=on">CXCR4↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=1247&wNotes=on">SDF1↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=304&wNotes=on">TGF-β↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=719&wNotes=on">α-SMA↓</a>, -->
<a href="tbResList.php?qv=142&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=142&tsv=1178&wNotes=on">MARK4↓</a> <!-- contributing to tumor growth, invasion, and metastasis-->
<br>
<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
- reactivate genes thereby inhibiting cancer cell growth(weak) :
<a href="tbResList.php?qv=142&tsv=984&wNotes=on">HDAC2↓</a>,
<a href="tbResList.php?qv=142&tsv=469&wNotes=on">DNMTs↓weak</a>,
<!--<a href="tbResList.php?qv=142&tsv=86&wNotes=on">DNMT3A↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=108&wNotes=on">EZH2↓</a>, -->
<a href="tbResList.php?qv=142&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?qv=142&wNotes=on&word=HSP">HSP↓</a>,
<!--<a href="tbResList.php?qv=142&tsv=506&wNotes=on">Sp proteins↓</a>, -->
<br>
<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?qv=142&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?qv=142&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?qv=142&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?qv=142&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?qv=142&tsv=894&wNotes=on">CDK4↓</a>,
<!--<a href="tbResList.php?qv=142&tsv=895&wNotes=on">CDK6↓</a>,-->
<br>
<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?qv=142&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?qv=142&tsv=324&wNotes=on">TumCI↓</a>,
<!--<a href="tbResList.php?qv=142&tsv=110&wNotes=on">FAK↓</a>, -->
<a href="tbResList.php?qv=142&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=142&tsv=96&wNotes=on">EMT↓</a>,
<!--<a href="tbResList.php?qv=142&tsv=1117&wNotes=on">TOP1↓</a>, -->
<!--<a href="tbResList.php?qv=142&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=142&tsv=129&wNotes=on">glycolysis</a>
/<a href="tbResList.php?qv=142&tsv=947&wNotes=on">Warburg Effect</a> and
<a href="tbResList.php?qv=142&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?qv=142&tsv=143&wNotes=on">HIF-1α↓??</a>,
<!--<a href="tbResList.php?qv=142&tsv=772&wNotes=on">PKM2↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=35&wNotes=on">cMyc↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=566&wNotes=on&word=GLUT">GLUT1↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=906&wNotes=on">LDH↓</a>, -->
<a href="tbResList.php?qv=142&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<!--<a href="tbResList.php?qv=142&tsv=773&wNotes=on">HK2↓</a>, -->
<a href="tbResList.php?qv=142&wNotes=on&word=PFK">PFKs↓</a>,
<!--<a href="tbResList.php?qv=142&wNotes=on&word=PDK">PDKs↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=847&wNotes=on">ECAR↓</a>, -->
<!--<a href="tbResList.php?qv=142&tsv=230&wNotes=on">OXPHOS↓</a>, -->
<a href="tbResList.php?qv=142&tsv=356&wNotes=on">GRP78↑</a>,
<!--<a href="tbResList.php?qv=142&tsv=1278&wNotes=on">Glucose↓</a>, -->
<a href="tbResList.php?qv=142&tsv=623&wNotes=on">GlucoseCon↓</a>
<br>
<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=142&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=142&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?qv=142&tsv=143&wNotes=on">HIF-1α↓</a>,
<!-- <a href="tbResList.php?qv=142&wNotes=on&word=NOTCH">Notch↓</a>, -->
<!-- <a href="tbResList.php?qv=142&wNotes=on&word=FGF">FGF↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=361&wNotes=on">PDGF↓</a>, -->
<a href="tbResList.php?qv=142&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<!-- <a href="tbResList.php?qv=142&&wNotes=on&word=ITG">Integrins↓</a>, -->
<br>
<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- inhibits Cancer Stem Cells (few references) :
<a href="tbResList.php?qv=142&tsv=795&wNotes=on">CSC↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=524&wNotes=on">CK2↓</a>, -->
<a href="tbResList.php?qv=142&tsv=141&wNotes=on">Hh↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=434&wNotes=on">GLi↓</a>, -->
<a href="tbResList.php?qv=142&tsv=124&wNotes=on">GLi1↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=677&wNotes=on">CD133↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=655&wNotes=on">CD24↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=342&wNotes=on">β-catenin↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=357&wNotes=on">n-myc↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=656&wNotes=on">sox2↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=222&wNotes=on">notch2↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=1024&wNotes=on">nestin↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=508&wNotes=on">OCT4↓</a>, -->
<br>
<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=142&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=142&tsv=4&wNotes=on">AKT↓</a>,
<!-- <a href="tbResList.php?qv=142&wNotes=on&word=JAK">JAK↓</a>, -->
<a href="tbResList.php?qv=142&wNotes=on&word=STAT">STAT↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=377&wNotes=on">Wnt↓</a>, -->
<!-- <a href="tbResList.php?qv=142&tsv=342&wNotes=on">β-catenin↓</a>, -->
<a href="tbResList.php?qv=142&tsv=9&wNotes=on">AMPK</a>,
<!-- <a href="tbResList.php?qv=142&tsv=475&wNotes=on">α↓</a>, -->
<a href="tbResList.php?qv=142&tsv=105&wNotes=on">ERK↓</a>,
<!-- <a href="tbResList.php?qv=142&tsv=1014&wNotes=on">5↓</a>, -->
<a href="tbResList.php?qv=142&tsv=168&wNotes=on">JNK</a>,
<br>
<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=142&tsv=1106&wNotes=on">chemo-sensitization</a>,
<a href="tbResList.php?qv=142&tsv=1171&wNotes=on">chemoProtective</a>,
<a href="tbResList.php?qv=142&tsv=1107&wNotes=on">RadioSensitizer</a>,
<a href="tbResList.php?qv=142&tsv=1185&wNotes=on">RadioProtective</a>,
<a href="tbResList.php?qv=142&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=142&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=142&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=142&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=142&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=142&tsv=1188&wNotes=on">CardioProtective</a>,
<br>
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=142&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a><br>
<br>
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Label</th>
<th>Primary Interpretation</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>Reactive oxygen species (ROS)</td>
<td>↓ ROS (dominant antioxidant effect)</td>
<td>↓ ROS</td>
<td>Driver</td>
<td>Antioxidant / redox buffering</td>
<td>Rosmarinic acid is a strong phenolic antioxidant; cancer effects are largely redox-modulatory rather than cytotoxic</td>
</tr>
<tr>
<td>2</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB activation</td>
<td>↓ inflammatory NF-κB tone</td>
<td>Secondary</td>
<td>Suppression of inflammatory survival signaling</td>
<td>NF-κB inhibition explains anti-inflammatory, anti-proliferative, and chemopreventive effects</td>
</tr>
<tr>
<td>3</td>
<td>MAPK signaling (ERK / JNK / p38)</td>
<td>↓ ERK; ↑ JNK/p38 (context-dependent)</td>
<td>↔ minimal</td>
<td>Secondary</td>
<td>Stress-modulated signaling</td>
<td>MAPK modulation reflects redox-sensitive signaling rather than direct kinase inhibition</td>
</tr>
<tr>
<td>4</td>
<td>Cell cycle regulation</td>
<td>↑ G0/G1 arrest (mild)</td>
<td>↔ spared</td>
<td>Phenotypic</td>
<td>Cytostatic growth control</td>
<td>Growth inhibition is modest and non-cytotoxic in most models</td>
</tr>
<tr>
<td>5</td>
<td>Apoptosis</td>
<td>↑ apoptosis (weak / context-dependent)</td>
<td>↓ apoptosis</td>
<td>Phenotypic</td>
<td>Threshold-dependent cell death</td>
<td>Apoptosis is not a dominant mechanism and usually requires high doses or co-stress</td>
</tr>
<tr>
<td>6</td>
<td>NRF2 antioxidant response</td>
<td>↑ NRF2 (adaptive)</td>
<td>↑ NRF2 (protective)</td>
<td>Adaptive</td>
<td>Antioxidant gene induction</td>
<td>NRF2 activation reflects reinforcement of antioxidant capacity</td>
</tr>
</table>