condition found tbRes List
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


-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



Glycolysis, Glycolysis: Click to Expand ⟱
Source:
Type:
Glycolysis is a metabolic pathway that converts glucose into pyruvate, producing a small amount of ATP (energy) in the process. It is a fundamental process for cellular energy production and occurs in the cytoplasm of cells. In normal cells, glycolysis is tightly regulated and is followed by aerobic respiration in the presence of oxygen, which allows for the efficient production of ATP.
In cancer cells, however, glycolysis is often upregulated, even in the presence of oxygen. This phenomenon is known as the Warburg Mutations in oncogenes (like MYC) and tumor suppressor genes (like TP53) can alter metabolic pathways, promoting glycolysis and other anabolic processes that support cell growth.effect.
Acidosis: The increased production of lactate from glycolysis can lead to an acidic microenvironment, which may promote tumor invasion and suppress immune responses.

Glycolysis is a hallmark of malignancy transformation in solid tumor, and LDH is the key enzyme involved in glycolysis.

Pathways:
-GLUTs, HK2, PFK, PK, PKM2, LDH, LDHA, PI3K/AKT/mTOR, AMPK, HIF-1a, c-MYC, p53, SIRT6, HSP90α, GAPDH, HBT, PPP, Lactate Metabolism, ALDO

Natural products targeting glycolytic signaling pathways https://pmc.ncbi.nlm.nih.gov/articles/PMC9631946/
Alkaloids:
-Berberine, Worenine, Sinomenine, NK007, Tetrandrine, N-methylhermeanthidine chloride, Dauricine, Oxymatrine, Matrine, Cryptolepine

Flavonoids: -Oroxyline A, Apigenin, Kaempferol, Quercetin, Wogonin, Baicalein, Chrysin, Genistein, Cardamonin, Phloretin, Morusin, Bavachinin, 4-O-methylalpinumisofavone, Glabridin, Icaritin, LicA, Naringin, IVT, Proanthocyanidin B2, Scutellarin, Hesperidin, Silibinin, Catechin, EGCG, EGC, Xanthohumol.

Non-flavonoid phenolic compounds:
Curcumin, Resveratrol, Gossypol, Tannic acid.

Terpenoids:
-Cantharidin, Dihydroartemisinin, Oleanolic acid, Jolkinolide B, Cynaropicrin, Ursolic Acid, Triptolie, Oridonin, Micheliolide, Betulinic Acid, Beta-escin, Limonin, Bruceine D, Prosapogenin A (PSA), Oleuropein, Dioscin.

Quinones:
-Thymoquinone, Lapachoi, Tan IIA, Emodine, Rhein, Shikonin, Hypericin

Others:
-Perillyl alcohol, HCA, Melatonin, Sulforaphane, Vitamin D3, Mycoepoxydiene, Methyl jasmonate, CK, Phsyciosporin, Gliotoxin, Graviola, Ginsenoside, Beta-Carotene.
Scientific Papers found: Click to Expand⟱
2686- BBR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Nor, NA
Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1↓,
cycE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,

2710- BBR,    Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells
- in-vitro, Ovarian, SKOV3
Warburg↓, berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly.
miR-145↑,
HK2↓, westernblot suggested that berberine could significantly down regulate the expression of HK2
TET3↑, Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene.
Glycolysis↓, Furthermore, the effect of berberine on glycolysis related enzymes was detected, the results of qRT-PCR and westernblot suggested that berberine could significantly down regulate the expression of HK2
PKM2↓, Western blot results showed down-expression of miR-145 reversed berberine's inhibition of HK2 expression. PKM2, pyruvate kinase M2; HK2, Hexokinase2; GLUT1, glucose transporter 1; LDH, lactate dehydrogenase; PFK2, phosphofructokinase 2; PDK1,
GLUT1↓,
LDH↓,
PFK2↓,
PDK1↓,

2709- BBR,    Berberine inhibits the glycolysis and proliferation of hepatocellular carcinoma cells by down-regulating HIF-1α
- in-vitro, HCC, HepG2
TumCP↓, After exposure to 100 μmol/L BBR, the proliferation, migration and invasion of HepG2 cells were reduced, along with apoptosis was increased, while the levels of glycolysis-related proteins were decreased
TumCMig↓,
TumCI↓,
Apoptosis↑,
Glycolysis↓, BBR inhibits proliferation and glycolysis of HCC cells in vivo
Hif1a↓, BBR can down-regulate HIF-1α in the hypoxic microenvironment, and hinder the proliferation and metastasis of breast cancer cell
GLUT1↓, treatment with 100μmol/L BBR for 48 h, the levels of GLUT1, HK2, PKM2, and LDHA mRNA were markedly reduced in HepG2 cells
HK2↓,
PKM2↓,
LDHA↓,

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.

932- BBR,    The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity
- in-vivo, Nor, NA
*glucoNG↓, These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis
*Glycolysis↑,
*NH3↑, inhibited ammonia detoxification
*NADPH/NADP+↑,
*ATP↓,
*toxicity↑, narrow margin between the expected benefits and toxicity

2335- BBR,    Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
- in-vitro, CRC, HT29 - in-vitro, CRC, HCT116 - in-vivo, NA, NA
PKM2↓, berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. Berberine inhibited PKM2 activity
Glycolysis↓, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes
p‑STAT3↓,
Bcl-2↓,
cycD1↓,
TumCG↓, n vivo experiments showed that tumor growth was inhibited in HT29 cell-bearing mice injected intraperitoneally with berberine (5 or 10 mg/kg body weight)
Ki-67↓, Berberine inhibited the proliferation index (Ki67 expression)
lactateProd↓, Berberine inhibited lactate production, glucose uptake, pyruvate production, and PKM2 activity in HWT tumor tissues, but no apparent effects were observed in both F244A mutant cells and I199S mutant tumor tissues
glucose↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   AMPK↑,1,   Apoptosis↑,1,   ATP↓,2,   Bax:Bcl2↑,1,   Bcl-2↓,2,   Casp3↑,1,   Casp9↑,1,   CCR7↓,1,   CD133↓,1,   CDK2↓,1,   CDK4↓,1,   ChemoSen↑,1,   COX2↓,1,   CSCs↓,1,   CXCR4↓,1,   cycD1↓,2,   cycE↓,1,   Diff↓,1,   DNAdam↑,1,   Dose?,1,   Dose↓,1,   Dose↑,1,   eff↑,3,   eff↝,1,   EGFR↓,1,   EMT↓,1,   ERK↓,1,   glucose↓,1,   GlucoseCon↓,2,   GLUT1↓,4,   Glycolysis↓,6,   Hif1a↓,3,   HK2↓,3,   IL6↓,1,   Inflam↓,1,   JAK2↓,1,   Ki-67↓,1,   lactateProd↓,1,   LDH↓,1,   LDHA↓,2,   MCP1↓,1,   MEK↓,1,   miR-145↑,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   mTOR↓,2,   p‑mTORC1↓,1,   n-MYC↓,1,   Nestin↓,1,   NOTCH↓,1,   p27↑,1,   PDK1↓,1,   PFK2↓,1,   PGE2↓,2,   PI3K↓,1,   PKM2↓,3,   PTEN↑,1,   RadioS↑,1,   Raf↓,1,   ROS↑,1,   p‑S6K↓,1,   selectivity↑,2,   SOX2↓,1,   STAT3↓,1,   p‑STAT3↓,1,   Telomerase↓,1,   TET3↑,1,   TumCCA↑,2,   TumCG↓,2,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,2,   uPA↓,1,   VEGF↓,1,   VEGFR2↓,1,   Warburg↓,2,  
Total Targets: 78

Results for Effect on Normal Cells:
ATP↓,1,   glucoNG↓,1,   Glycolysis↑,1,   NADPH/NADP+↑,1,   NH3↑,1,   toxicity↑,1,  
Total Targets: 6

Scientific Paper Hit Count for: Glycolysis, Glycolysis
7 Berberine
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:41  Target#:129  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page