Database Query Results : Berberine, , GlucoseCon

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)


GlucoseCon, Glucose Consumption: Click to Expand ⟱
Source:
Type:
Glucose consumption is often elevated in cancer cells due to an increased reliance on glycolysis for energy production, even in the presence of oxygen. This phenomenon, known as the Warburg effect, is a metabolic shift that allows cancer cells to rapidly proliferate and survive in nutrient-poor environments.

The increased glucose consumption in cancer cells can be detected using positron emission tomography (PET) scans, which measure the uptake of a glucose analog labeled with a radioactive tracer.
Scientific Papers found: Click to Expand⟱
2708- BBR,    Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells
- in-vitro, CRC, HCT116
TumCG↓, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines
GlucoseCon↓,
GLUT1↓,
LDHA↓, berberine inhibited the mRNA levels of LDHA and HK2 in a concentration-dependent manner
HK2↓,
Hif1a↓, protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines
mTOR↓, mTOR signaling previously reported to regulate HIF‑1α protein synthesis was further found to be suppressed by berberine.
Glycolysis↓, berberine inhibits overactive glucose metabolism of colon cancer cells via suppressing mTOR‑depended HIF‑1α protein synthesis

2707- BBR,    Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
GLUT1↓, BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1
Akt↓, and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines
mTOR↓,
ATP↓, BBR-induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation
GlucoseCon↓,
TumCP↓,
Warburg↓, antineoplastic effect of BBR may involve the reversal of the Warburg effect
selectivity↑, The results demonstrated that the colony-forming capacity was slightly inhibited in Hs 578Bst normal breast cells following BBR treatment, but significantly inhibited in both cancer cell lines.
TumCCA↑, BBR effectively induced cell cycle arrest at the G2M phase
Glycolysis↓, Notably, our preliminary experiments identified that BBR strongly decreased the glucose uptake ability of HepG2 and MCF7 cell lines, therefore, it was hypothesized that BBR may interfere with tumor progression by inhibiting glycolysis.


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

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 2,   Glycolysis↓, 2,   HK2↓, 1,   LDHA↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 2,   TumCG↓, 1,  

Migration ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Drug Metabolism & Resistance ⓘ

selectivity↑, 1,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GlucoseCon, Glucose Consumption
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:41  Target#:623  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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