Database Query Results : Berberine, , EZH2

BBR, Berberine: Click to Expand ⟱

Features:

Berberine 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.
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.

– 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.
– Despite the low bioavailability, berberine is still pharmacologically active, and its metabolites may also contribute to its overall effects.

• Effective Dosage in Studies
– Many clinical trials or preclinical studies use dosages in the range of 500 to 1500 mg per day, typically administered in divided doses.
– Therefore, to obtain a bioactive dose of berberine, supplementation in a standardized extract form is necessary.

-IC50 in cancer cell lines: Approximately 10–100 µM (commonly around 20–50 µM in many models)
-IC50 in normal cell lines: Generally higher (often above 100 µM), although this can vary with cell type
- In vivo studies: Dosing regimens in animal models generally range from about 50 to 200 mg/kg
- very effective AChE inhibitor (Alzheimers)
- Berberine may enhance the effects of blood-thinning medications like warfarin and aspirin.

-Note half-life reports vary 2.5-90hrs?.
-low solubility of apigenin in water : BioAv
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, EZH2↓, P53↑, HSP↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, CD133↓, β-catenin↓, n-myc↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells

Rank	Pathway / Target Axis	Direction	Primary Effect	Notes / Cancer Relevance	Ref
1	AMPK → mTOR axis	↑ AMPK / ↓ mTOR signaling	Metabolic stress + growth suppression	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	(ref)
2	Mitochondrial dysfunction / ROS generation	↑ ROS / mitochondrial stress	Upstream metabolic trigger	Berberine inhibits mitochondrial function, increases ROS, and contributes to AMPK activation and downstream apoptosis	(ref)
3	Mitochondrial apoptosis (cytochrome c release)	↑ cytochrome c release	Intrinsic death signaling	Oral cancer model: berberine reduces mitochondrial membrane potential, releases cytochrome c, activates caspase-3	(ref)
4	Intrinsic apoptosis (caspase-3 activation)	↑ caspase-3 activation	Programmed cell death	Same oral cancer study documents caspase-3 activation as a key execution marker	(ref)
5	NF-κB signaling (p65 activation)	↓ NF-κB activation	Reduced pro-survival transcription	Colon cancer model reports inhibition of p65 phosphorylation; interpreted as secondary to metabolic/redox stress	(ref)
6	Cell cycle control	↑ G1 arrest	Proliferation blockade	Prostate cancer model: berberine induces G1-phase cell cycle arrest and caspase-3–dependent apoptosis	(ref)
7	Hypoxia / glycolysis signaling (HIF-1α)	↓ HIF-1α protein	Warburg / glycolysis suppression	Berberine suppresses mTOR and reduces HIF-1α protein expression downstream of AMPK activation	(ref)
8	Angiogenesis signaling (HIF-1α → VEGF axis)	↓ VEGF signaling	Reduced vascular support	Lung cancer study: berberine suppresses VEGF signaling alongside HIF-1α inhibition	(ref)
9	PI3K–AKT–mTOR signaling	↓ PI3K / AKT / mTOR	Survival pathway suppression	Gastric cancer paper: berberine represses PI3K/AKT/mTOR signaling and improves chemosensitivity	(ref)
10	Migration / invasion programs	↓ migration & invasion	Anti-metastatic phenotype	Tongue SCC model: berberine suppresses migration and invasion with associated signaling changes	(ref)
11	Telomerase (hTERT) / immortalization axis	↓ hTERT-related signaling	Reduced proliferative capacity	Lung cancer study includes AP-2/hTERT regulatory axis modulation by berberine	(ref)
12	In vivo tumor suppression	↓ tumorigenesis	Demonstrated anti-tumor effect	Colon tumorigenesis model confirms reduced proliferation and tumor burden with berberine	(ref)

EZH2, enhancer of zeste homolog 2 (Drosophila): Click to Expand ⟱

Source: CGL-Driver Genes

Type: Oncogene

EZH2 (Enhancer of Zeste Homolog 2) is a gene that encodes a protein which is a key component of the Polycomb Repressive Complex 2 (PRC2). This complex is involved in the regulation of gene expression through histone methylation, specifically the trimethylation of histone H3 at lysine 27 (H3K27me3), which leads to transcriptional repression of target genes.
EZH2 is often overexpressed in various types of cancers, including breast, prostate, and lymphoma. This overexpression can lead to the silencing of tumor suppressor genes, contributing to uncontrolled cell proliferation and survival.

EZH2 is biology-first; its biomarker value is a readout of epigenetic state.

Scientific Papers found: Click to Expand⟱

2704-

BBR,

Inhibitory Effect of Berberine on Zeste Homolog 2 (Ezh2) Enhancement in Human Esophageal Cell Lines

in-vitro,

ESCC,

KYSE450

EZH2↓, Berberine-induced inhibition of Ezh2 expression led to inhibition of cell proliferation by G1 phase cell cycle arrest and induced anti-invasive properties of KYSE450 cells in Boyden chamber assays.
AXL↓, Berberine treatment also resulted in strong transcriptional reduction of the AXL receptor kinase.

2703-

BBR,

CUR,

SFN,

UA,

GamB

Naturally occurring anti-cancer agents targeting EZH2

Review,

Var,

EZH2↓, In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators.

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:

Transcription & Epigenetics ⓘ

EZH2↓, 2,

Migration ⓘ

AXL↓, 1,

Clinical Biomarkers ⓘ

EZH2↓, 2,
Total Targets: 3

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: EZH2, enhancer of zeste homolog 2 (Drosophila)

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells