Berberine / TNF-α Cancer Research Results

BBR, Berberine: Click to Expand ⟱
Features:

Berberine — Berberine is a protoberberine/isoquinoline alkaloid natural product found in plants such as Coptis, Berberis, and Phellodendron. It is a small-molecule phytochemical with pleiotropic metabolic, anti-inflammatory, and anticancer signaling effects rather than a single highly selective target profile. Its standard abbreviation is BBR. In oncology it is best classified as a multitarget natural-product lead compound and adjunct-sensitizer candidate, with strong preclinical evidence but no established standard anticancer regulatory use. Its translational profile is shaped by very low conventional oral bioavailability, extensive first-pass metabolism, broad tissue distribution, and substantial context dependence between cancer-cell pro-death effects and normal-cell cytoprotective redox effects.

Primary mechanisms (ranked):

  1. AMPK-centered metabolic stress with mitochondrial dysfunction, ATP depletion, and apoptosis/autophagy induction
  2. Suppression of aerobic glycolysis and hypoxia signaling, including HIF-1α, GLUT1, HK2, LDHA, and PKM2-linked tumor metabolism
  3. Anti-proliferative cell-cycle control with cyclin/CDK suppression and tumor suppressor reactivation
  4. Inhibition of PI3K/AKT, MAPK/ERK, JAK/STAT, and NF-κB inflammatory-survival signaling
  5. Anti-metastatic and anti-EMT activity via Wnt/β-catenin, TGF-β/Smad, FAK/RhoA/ROCK, MMPs, and CXCR4-related programs
  6. Pro-oxidant mitochondrial ROS elevation and ER-stress/caspase signaling in many cancer models, with opposite antioxidant/NRF2-supportive effects in some normal-cell and non-cancer settings
  7. Context-dependent chemosensitization and radiosensitization, including effects on hypoxia signaling and DNA-repair competence
  8. Emerging ferroptosis-related activity in some tumor models, but not a universal dominant mechanism across berberine biology

Bioavailability / PK relevance: Conventional oral berberine has poor systemic bioavailability, often cited as below 1% in animal studies, because of limited absorption, P-glycoprotein efflux, first-pass intestinal/hepatic metabolism, and self-aggregation. Human exposure is usually in the low ng/mL plasma range with conventional dosing, while multiple metabolites may contribute to activity. Tissue distribution can exceed plasma levels, but PK remains a major clinical translation constraint.

In-vitro vs systemic exposure relevance: Many anticancer in-vitro studies use roughly 10–100 µM, commonly around 20–50 µM, which usually exceeds readily achievable conventional plasma exposure after standard oral dosing. Therefore, direct translation of cell-culture potency to systemic monotherapy expectations is limited unless local gut exposure, tissue accumulation, metabolite contribution, formulation enhancement, or combination use is specifically relevant.

Clinical evidence status: Strong preclinical and mechanistic evidence; limited early human oncology/chemoprevention evidence; no established phase III anticancer efficacy standard and no mainstream regulatory approval as an anticancer drug. Current clinical relevance is best viewed as investigational and adjunct-oriented rather than proven standalone oncology therapy.

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↓">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)


TNF-α, TNF-α: Click to Expand ⟱
Source: HalifaxProj (block)
Type:
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a complex role in cancer biology. It is primarily produced by activated macrophages and is involved in systemic inflammation. TNF-α is a pro-inflammatory cytokine that can promote inflammation, which is a known factor in cancer development.
Overall, the expression of TNF-α in cancers is often linked to inflammation, tumor progression, and the tumor microenvironment.
Scientific Papers found: Click to Expand⟱
2705- BBR,    Mechanism underlying berberine's effects on HSP70/TNFα under heat stress: Correlation with the TATA boxes
- in-vivo, Nor, NA - in-vitro, Nor, PC12
HSP70/HSPA5↓, TNF-α↓,
2699- BBR,    Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line
- in-vitro, Lung, A549
HDAC↓, TumCCA↑, TNF-α↓, COX2↓, MMP2↓, MMP9↓, P21↑, P53↑, Casp↑, ac‑H3↑, ac‑H4↑, ROS↑, MMP↓,
4274- BBR,    Berberine exerts antidepressant effects in vivo and in vitro through the PI3K/AKT/CREB/BDNF signaling pathway
- in-vivo, NA, NA
*IL1β↓, *IL6↓, *TNF-α↓, *CRP↓, *CREB↑, *BDNF↑,
3684- BBR,    Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies
- Review, AD, NA
*Inflam↓, *antiOx↓, *AChE↓, *BChE↓, *MAOA↓, *MAOB↓, *lipid-P↓, *GSH↑, *ROS↓, *APP↓, *BACE↓, *p‑tau↓, *NF-kB↓, *TNF-α↓, *IL1β↓, *MAPK↓, *PI3K↓, *Akt↓, *neuroP↑, *memory↑,
1092- BBR,    Berberine as a Potential Anticancer Agent: A Comprehensive Review
- Review, NA, NA
Apoptosis↑, TumCCA↑, TumAuto↑, TumCI↓, IL1↓, IL6↓, TNF-α↓, LDH↓, P2X7↓, proCasp1↓, Casp1↓, ASC↓,
2677- BBR,    Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring
- in-vivo, Diabetic, NA
*hepatoP↑, *LC3II↑, *Beclin-1↑, *AMPK↑, *mTOR↑, *ER Stress↓, *CHOP↓, *JNK↓, *ROS↓, *Inflam↓, *BG↓, *SOD↑, *GPx↑, *Catalase↑, *IL10↑, *IL6↓, *TNF-α↓, *ALAT↓, *AST↓, *ALP↓,
2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, AntiCan↑, Apoptosis↑, TumAuto↑, TumCCA↑, TumMeta↓, TumCI↓, eff↑, eff↑, CD4+↓, TNF-α↓, IL1↓, BioAv↓, BioAv↓, other↓, AMPK↑, MAPK↓, NF-kB↓, IL6↓, MCP1↓, PGE2↓, COX2↓, *ROS↓, *antiOx↑, *GPx↑, *Catalase↑, AntiTum↑, TumCP↓, angioG↓, Fas↑, FasL↑, ROS↑, ATM↑, P53↑, RB1↑, Casp9↑, Casp8↑, Casp3↓, BAX↑, Bcl-2↓, Bcl-xL↓, IAP1↓, XIAP↓, survivin↓, MMP2↓, MMP9↓, CycB/CCNB1↓, CDC25↓, CDC25↓, Cyt‑c↑, MMP↓, RenoP↑, mTOR↓, MDM2↓, LC3II↑, ERK↓, COX2↓, MMP3↓, TGF-β↓, EMT↑, ROCK1↓, FAK↓, RAS↓, Rho↓, NF-kB↓, uPA↓, MMP1↓, MMP13↓, ChemoSen↑,
1399- BBR,  Rad,    Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review
- Review, NA, NA
*ROS↓, *MDA↓, *TNF-α↓, *TGF-β↓, *IL10↑, ROS↑, DNAdam↑, mtDam↑, MMP↓, Apoptosis↑, TumCCA↑, Hif1a↓, VEGF↓, RadioS↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

CDC25↓, 2,   MMP↓, 3,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   LDH↓, 1,  

Cell Death ⓘ

Apoptosis↑, 3,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp1↓, 1,   proCasp1↓, 1,   Casp3↓, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   Fas↑, 1,   FasL↑, 1,   IAP1↓, 1,   MAPK↓, 1,   MDM2↓, 1,   P2X7↓, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   other↓, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↓, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

ATM↑, 1,   DNAdam↑, 1,   P53↑, 2,  

Cell Cycle & Senescence ⓘ

CycB/CCNB1↓, 1,   P21↑, 1,   RB1↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   ERK↓, 1,   HDAC↓, 1,   mTOR↓, 1,   RAS↓, 1,  

Migration ⓘ

FAK↓, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 2,   MMP3↓, 1,   MMP9↓, 2,   Rho↓, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TumCI↓, 2,   TumCP↓, 1,   TumMeta↓, 1,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   CD4+↓, 1,   COX2↓, 3,   IL1↓, 2,   IL6↓, 2,   Inflam↓, 1,   MCP1↓, 1,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   ChemoSen↑, 1,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 2,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   RenoP↑, 1,  
Total Targets: 78

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 1,   lipid-P↓, 1,   MDA↓, 1,   ROS↓, 4,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   CREB↑, 1,  

Cell Death ⓘ

Akt↓, 1,   JNK↓, 1,   MAPK↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   ER Stress↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↑, 1,   PI3K↓, 1,  

Migration ⓘ

APP↓, 1,   TGF-β↓, 1,  

Immune & Inflammatory Signaling ⓘ

CRP↓, 1,   IL10↑, 2,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 2,   NF-kB↓, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,   BDNF↑, 1,   MAOA↓, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

BACE↓, 1,   MAOB↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BG↓, 1,   CRP↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

hepatoP↑, 1,   memory↑, 1,   neuroP↑, 1,  
Total Targets: 46

Scientific Paper Hit Count for: TNF-α, TNF-α
8 Berberine
1 Radiotherapy/Radiation
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#:309  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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