Description: <b>Berberine</b> is a chemical found in some plants like European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Berberine is a bitter-tasting and yellow-colored chemical.<br>
Coptis (commonly referring to Coptidis Rhizoma, a traditional Chinese medicinal herb) contains bioactive alkaloids (most notably berberine and coptisine) that have been studied for their pharmacological effects—including their influence on reactive oxygen species (ROS) and related pathways.<br>
<br>
– Berberine is known for its relatively low oral bioavailability, often cited at less than 1%. This low bioavailability is mainly due to poor intestinal absorption and active efflux by transport proteins such as P-glycoprotein.<br>
– Despite the low bioavailability, berberine is still pharmacologically active, and its metabolites may also contribute to its overall effects.<br>
<br>
• Effective Dosage in Studies<br>
– Many clinical trials or preclinical studies use dosages in the range of 500 to 1500 mg per day, typically administered in divided doses.<br>
– Therefore, to obtain a bioactive dose of berberine, supplementation in a standardized extract form is necessary.<br>
<br>
-IC50 in cancer cell lines: Approximately 10–100 µM (commonly around 20–50 µM in many models)<br>
-IC50 in normal cell lines: Generally higher (often above 100 µM), although this can vary with cell type<br>
- In vivo studies: Dosing regimens in animal models generally range from about 50 to 200 mg/kg<br>
- very effective AChE inhibitor (Alzheimers)<br>
- Berberine may enhance the effects of blood-thinning medications like warfarin and aspirin. <br>
<br>
<br>
-Note <a href="tbResList.php?qv=41&tsv=1109&wNotes=on&exSp=open">half-life</a> reports vary 2.5-90hrs?.<br>
-low solubility of apigenin in water :
<a href="tbResList.php?qv=41&tsv=792&wNotes=on&exSp=open">BioAv</a>
<br>
Pathways:<br>
<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- induce
<a href="tbResList.php?qv=41&tsv=275&wNotes=on">ROS</a> production<br>
- ROS↑ related:
<a href="tbResList.php?&qv=41&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?&qv=41&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?&qv=41&tsv=38&wNotes=on">Ca+2↑</a>,
<a href="tbResList.php?&qv=41&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?&qv=41&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?&qv=41&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?&qv=41&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?&qv=41&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?&qv=41&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=41&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?&qv=41&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<br>
- Raises
<a href="tbResList.php?&qv=41&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?&qv=41&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?&qv=41&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?&qv=41&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?&qv=41&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=41&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?&qv=41&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?&qv=41&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?&qv=41&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?&qv=41&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?&qv=41&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?&qv=41&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?&qv=41&tsv=368&wNotes=on&word=IL8↓">IL-8↓</a>
<br>
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.<br>
<!-- GROWTH/METASTASES : EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1, uPA↓, VEGF↓, ERK↓-->
- inhibit Growth/Metastases :
<a href="tbResList.php?&qv=41&tsv=96&wNotes=on"EMT↓</a>,
<a href="tbResList.php?&qv=41&tsv=204&wNotes=on">MMPs↓</a>,
<a href="tbResList.php?&qv=41&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?&qv=41&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?&qv=41&tsv=415&wNotes=on">IGF-1↓</a>,
<a href="tbResList.php?&qv=41&tsv=428&wNotes=on">uPA↓</a>,
<a href="tbResList.php?&qv=41&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=41&tsv=1284&wNotes=on">ROCK1↓</a>,
<a href="tbResList.php?&qv=41&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=41&tsv=273&wNotes=on">RhoA↓</a>,
<a href="tbResList.php?&qv=41&tsv=214&wNotes=on">NF-κB↓</a>,
<a href="tbResList.php?&qv=41&tsv=79&wNotes=on">CXCR4↓</a>,
<a href="tbResList.php?&qv=41&tsv=304&wNotes=on">TGF-β↓</a>,
<a href="tbResList.php?&qv=41&tsv=719&wNotes=on">α-SMA↓</a>,
<a href="tbResList.php?&qv=41&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=41&tsv=140&wNotes=on">HDAC↓</a>,
<a href="tbResList.php?qv=41&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=41&tsv=108&wNotes=on">EZH2↓</a>,
<a href="tbResList.php?qv=41&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?&qv=41&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=41&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?&qv=41&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?&qv=41&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?&qv=41&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?&qv=41&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?&qv=41&tsv=895&wNotes=on">CDK6↓</a>,
<br>
<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?&qv=41&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?&qv=41&tsv=324&wNotes=on">TumCI↓</a>,
<a href="tbResList.php?&qv=41&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=41&tsv=105&wNotes=on">ERK↓</a>,
<br>
<!-- GLYCOLYSIS : ATP↓, HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓, lactateProd, OXPHOS -->
- inhibits
<a href="tbResList.php?qv=41&tsv=129&wNotes=on">glycolysis</a>
/<a href="tbResList.php?qv=41&tsv=947&wNotes=on">Warburg Effect</a> and
<a href="tbResList.php?qv=41&tsv=21&wNotes=on&word=ATP↓">ATP depletion</a> :
<a href="tbResList.php?&qv=41&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=41&tsv=772&wNotes=on">PKM2↓</a>,
<a href="tbResList.php?&qv=41&tsv=35&wNotes=on">cMyc↓</a>,
<a href="tbResList.php?&qv=41&tsv=566&wNotes=on&word=GLUT">GLUT1↓</a>,
<a href="tbResList.php?&qv=41&tsv=906&wNotes=on">LDH↓</a>,
<a href="tbResList.php?&qv=41&tsv=175&wNotes=on&word=LDH">LDHA↓</a>,
<a href="tbResList.php?&qv=41&tsv=773&wNotes=on">HK2↓</a>,
<a href="tbResList.php?&qv=41&wNotes=on&word=PFK">PFKs↓</a>,
<a href="tbResList.php?&qv=41&wNotes=on&word=PDK">PDKs↓</a>,
<a href="tbResList.php?&qv=41&tsv=1278&wNotes=on">Glucose↓</a>,
<a href="tbResList.php?&qv=41&tsv=623&wNotes=on">GlucoseCon↓</a>
<br>
<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=41&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=41&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=41&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=41&wNotes=on&word=NOTCH">Notch↓</a>,
<a href="tbResList.php?&qv=41&wNotes=on&word=FGF">FGF↓</a>,
<a href="tbResList.php?&qv=41&tsv=361&wNotes=on">PDGF↓</a>,
<a href="tbResList.php?&qv=41&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<a href="tbResList.php?&qv=41&&wNotes=on&word=ITG">Integrins↓</a>,
<br>
<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- inhibits Cancer Stem Cells :
<a href="tbResList.php?qv=41&tsv=795&wNotes=on">CSC↓</a>,
<a href="tbResList.php?qv=41&tsv=141&wNotes=on">Hh↓</a>,
<a href="tbResList.php?qv=41&tsv=124&wNotes=on">GLi1↓</a>,
<a href="tbResList.php?qv=41&tsv=677&wNotes=on">CD133↓</a>,
<a href="tbResList.php?qv=41&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=41&tsv=357&wNotes=on">n-myc↓</a>,
<a href="tbResList.php?qv=41&tsv=656&wNotes=on">sox2↓</a>,
<a href="tbResList.php?qv=41&tsv=222&wNotes=on">notch2↓</a>,
<a href="tbResList.php?qv=41&tsv=1024&wNotes=on">nestin↓</a>,
<a href="tbResList.php?qv=41&tsv=508&wNotes=on">OCT4↓</a>,
<br>
<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=41&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=41&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=41&wNotes=on&word=JAK">JAK↓</a>,
<a href="tbResList.php?qv=41&wNotes=on&word=STAT">STAT↓</a>,
<a href="tbResList.php?qv=41&tsv=377&wNotes=on">Wnt↓</a>,
<a href="tbResList.php?qv=41&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=41&tsv=9&wNotes=on">AMPK↓</a>,
<a href="tbResList.php?qv=41&tsv=475&wNotes=on">α↓</a>,
<a href="tbResList.php?qv=41&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=41&tsv=168&wNotes=on">JNK</a>,
<br>
<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=41&tsv=1106&wNotes=on">chemo-sensitization</a>,
<a href="tbResList.php?qv=41&tsv=1171&wNotes=on">chemoProtective</a>,
<a href="tbResList.php?qv=41&tsv=1107&wNotes=on">RadioSensitizer</a>,
<a href="tbResList.php?qv=41&tsv=1185&wNotes=on">RadioProtective</a>,
<a href="tbResList.php?qv=41&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=41&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=41&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=41&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=41&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=41&tsv=1188&wNotes=on">CardioProtective</a>,
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=41&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 / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>
<tr>
<td>1</td>
<td>AMPK → mTOR axis</td>
<td>↑ AMPK / ↓ mTOR signaling</td>
<td>Metabolic stress + growth suppression</td>
<td>In vivo/in vitro colon tumorigenesis model: berberine activates AMPK, inhibits mTOR signaling and reduces proliferation/tumorigenesis, growth suppression, autophagy, HIF-1α ↓, glycolysis ↓, berberine’s known mitochondrial/energetic effects</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4504840/">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Mitochondrial dysfunction / ROS generation</td>
<td>↑ ROS / mitochondrial stress</td>
<td>Upstream metabolic trigger</td>
<td>Berberine inhibits mitochondrial function, increases ROS, and contributes to AMPK activation and downstream apoptosis</td>
<td><a href="https://www.nature.com/articles/aps2012161">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Mitochondrial apoptosis (cytochrome c release)</td>
<td>↑ cytochrome c release</td>
<td>Intrinsic death signaling</td>
<td>Oral cancer model: berberine reduces mitochondrial membrane potential, releases cytochrome c, activates caspase-3</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/17970083/">(ref)</a></td>
</tr>
<tr>
<td>4</td>
<td>Intrinsic apoptosis (caspase-3 activation)</td>
<td>↑ caspase-3 activation</td>
<td>Programmed cell death</td>
<td>Same oral cancer study documents caspase-3 activation as a key execution marker</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/17970083/">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>NF-κB signaling (p65 activation)</td>
<td>↓ NF-κB activation</td>
<td>Reduced pro-survival transcription</td>
<td>Colon cancer model reports inhibition of p65 phosphorylation; interpreted as secondary to metabolic/redox stress</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4504840/">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Cell cycle control</td>
<td>↑ G1 arrest</td>
<td>Proliferation blockade</td>
<td>Prostate cancer model: berberine induces G1-phase cell cycle arrest and caspase-3–dependent apoptosis</td>
<td><a href="https://aacrjournals.org/mct/article/5/2/296/285475/Berberine-a-natural-product-induces-G1-phase-cell">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>Hypoxia / glycolysis signaling (HIF-1α)</td>
<td>↓ HIF-1α protein</td>
<td>Warburg / glycolysis suppression</td>
<td>Berberine suppresses mTOR and reduces HIF-1α protein expression downstream of AMPK activation</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6521278/">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (HIF-1α → VEGF axis)</td>
<td>↓ VEGF signaling</td>
<td>Reduced vascular support</td>
<td>Lung cancer study: berberine suppresses VEGF signaling alongside HIF-1α inhibition</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069240">(ref)</a></td>
</tr>
<tr>
<td>9</td>
<td>PI3K–AKT–mTOR signaling</td>
<td>↓ PI3K / AKT / mTOR</td>
<td>Survival pathway suppression</td>
<td>Gastric cancer paper: berberine represses PI3K/AKT/mTOR signaling and improves chemosensitivity</td>
<td><a href="https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.616251/full">(ref)</a></td>
</tr>
<tr>
<td>10</td>
<td>Migration / invasion programs</td>
<td>↓ migration & invasion</td>
<td>Anti-metastatic phenotype</td>
<td>Tongue SCC model: berberine suppresses migration and invasion with associated signaling changes</td>
<td><a href="https://www.sciencedirect.com/science/article/pii/S0304383509000640">(ref)</a></td>
</tr>
<tr>
<td>11</td>
<td>Telomerase (hTERT) / immortalization axis</td>
<td>↓ hTERT-related signaling</td>
<td>Reduced proliferative capacity</td>
<td>Lung cancer study includes AP-2/hTERT regulatory axis modulation by berberine</td>
<td><a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069240">(ref)</a></td>
</tr>
<tr>
<td>12</td>
<td>In vivo tumor suppression</td>
<td>↓ tumorigenesis</td>
<td>Demonstrated anti-tumor effect</td>
<td>Colon tumorigenesis model confirms reduced proliferation and tumor burden with berberine</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4504840/">(ref)</a></td>
</tr>
</table>