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



ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
2680- BBR,  PDT,    Photodynamic therapy-triggered nuclear translocation of berberine from mitochondria leads to liver cancer cell death
- in-vitro, Liver, HUH7
TumCD↑, blue light irradiation (488 nm). The results showed that berberine rapidly translocated from the mitochondria to the nucleus upon light exposure, ultimately inducing cell death in SNU449 and Huh7 cells.
ROS↑, Additionally, we observed a significant increase in reactive oxygen species, linking the phototoxic effects to oxidative stress
TumCCA↑, indicating cell cycle arrest following treatment with berberine and PDT
ER Stress↑, Western blotting confirmed that ER stress was significantly induced

2689- BBR,    Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells
- in-vitro, Nor, PC12 - in-vitro, AD, NA - in-vitro, Stroke, NA
*ROS↓, In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells.
*lipid-P↓,
*DNAdam↓, Berberine significantly diminished glutamate-induced DNA fragmentation
*GSH↑,
*SOD↑,
*eff↑, This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer’s disease), seizures, and stroke.
*cl‑Casp3↓, Berberine significantly decreased cleaved caspase-3 and bax/bcl-2 expressions in the glutamate-injured cells
*BAX↓,
*neuroP↑, the current study demonstrated that berberine exerts neuroprotective effects against glutamate-induced N2a and PC12 cytotoxicity via antioxidant and anti-apoptotic mechanisms
*Dose↝, the protective effect of berberine was more significant at lower concentrations and decreased with increasing concentration.
*Ca+2↓, Nadjafi et al demonstrated that berberine protects OLN-93 oligodendrocytes against ischemic-induced cell death by attenuating the intracellular Ca2+ overload similar to the NMDA or the AMPA/kainate receptors antagonists

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↑,

2681- BBR,  PDT,    Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells
- in-vitro, Melanoma, NA
Apoptosis↑, BBR-PDT induced apoptosis via up-regulating the expression of cleaved caspase-3 protein.
cl‑Casp3↑,
LC3s↑, LC3-related autophagy level was upregulated in MMCs with BBR-PDT.
ER Stress↑, BBR-PDT activated endoplasmic reticulum (ER) stress, involving a dramatic increase in reactive oxygen species (ROS).
ROS↑,
CHOP↑, knockdown of CHOP protein expression inhibited apoptosis, autophagy and ER stress levels caused by BBR-PDT, suggesting that CHOP protein may be related to apoptosis, autophagy and ER stress in MMCs with BBR-PDT

2679- BBR,    Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer’s Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress
- in-vivo, AD, NA
*cognitive↑, berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer’s disease (3 × Tg AD) mice.
PERK↓, berberine treatment may inhibit PERK/eIF2α signaling-mediated BACE1 translation, thus reducing Aβ production and resultant neuronal apoptosis
*eIF2α↓,
*neuroP↑, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress.
*ER Stress↓,
*ROS↓,

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↑, berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM)
*LC3II↑, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats.
*Beclin-1↑,
*AMPK↑,
*mTOR↑,
*ER Stress↓, It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation.
*CHOP↓,
*JNK↓,
*ROS↓,
*Inflam↓,
*BG↓, Oral supplementation of diabetic rats either by Lip-BBR or Vild, 10 mg/kg of each, significantly (p < 0.001) lowered the blood glucose levels of tested diabetic rats compared to the diabetic group.
*SOD↑, when the diabetic rats received Lip-BBR, the decrements were less pronounced compared to the diabetic group by 1.16 fold, 2.52 fold, and 67.57% for SOD, GPX, and CAT, respectively.
*GPx↑,
*Catalase↑,
*IL10↑, Treatment of the diabetic rats with Lip-BBR significantly (p < 0.001) elevated serum IL-10 levels by 37.01% compared with diabetic rats.
*IL6↓, Oral supplementation of Lip-BBR could markedly (p < 0.0001) reduce the elevated serum levels of IL-6 and TNF-α when it is used as a single treatment by 55.83% and 49.54%,
*TNF-α↓,
*ALAT↓, ALT, AST, and ALP in the diabetic group were significantly higher (p < 0.0001) by 88.95%, 81.64%, and 1.8 fold, respectively, compared with those in the control group, but this was reversed by the treatment with Lip-BBR
*AST↓,
*ALP↓,

2676- BBR,    Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress
- in-vivo, Nor, NA - in-vivo, CardioV, NA
*cardioP↑, Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage.
*ROS↓,
*ER Stress↓, pretreatment with BBR suppressed MI/R-induced ER stress
*p‑PERK↓, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues.
*p‑eIF2α↓,
*ATF4↓,
CHOP↓,
*JAK2↑, Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues
*STAT3↑,
*UPR↓, Therefore, reducing excessive UPR, also referred to as ER stress, is of great importance in ameliorating MI/R injury.

2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1↓,
PGE2↓,
COX2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents

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↓, BBR represses total HDAC and also class I, II, and IV HDAC activity through hyperacetylation of histones.
TumCCA↑, BBR triggers positive regulation of the sub-G0/G1 cell cycle progression phase in A549 cells.
TNF-α↓, BBR downregulates oncogenes (TNF-α, COX-2, MMP-2, and MMP-9) and upregulates tumor suppressor genes (p21 and p53) mRNA and protein expressions.
COX2↓,
MMP2↓, BBR Induces Downregulation of MMP-2 and MMP-9
MMP9↓,
P21↑,
P53↑,
Casp↑, triggered the caspase cascade apoptotic pathway in A549 cells
ac‑H3↑, BBR Increases the Acetylation State of Histones H3 and H4.
ac‑H4↑,
ROS↑, BBR Induces ROS Generation, Δψm Alteration, Membrane Loss, and Nuclear Fragmentation
MMP↓,

1376- BBR,  immuno,    Berberine sensitizes immune checkpoint blockade therapy in melanoma by NQO1 inhibition and ROS activation
- in-vivo, Melanoma, NA
OS↑, BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice.
ROS↑,
NQO1↓,
ICD↑,

1387- BBR,    Antitumor Activity of Berberine by Activating Autophagy and Apoptosis in CAL-62 and BHT-101 Anaplastic Thyroid Carcinoma Cell Lines
- in-vitro, Thyroid, CAL-62
TumCG↓,
Apoptosis↑,
LC3B↑, LC3B-II
ROS↑,
PI3K↓,
Akt↓,
mTOR↓,

1386- BBR,    Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓,
ROS↑,
JNK↑,
MMP↓,
Bcl-2↓,
BAX↑,
Cyt‑c↑, increased the release of cytochrome c
AIF↝,

1385- BBR,  5-FU,    Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
eff↓, Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents
ROS↑, LDB mildly while HDB greatly stimulated ROS generation BBR-induced ROS generation may activate the antioxidant response therefore to promote cancer cell proliferation.
TumCP↑,
NRF2↑,
ChemoSen↓, These findings revealed a potential negative impact of BBR on its adjuvant anti-breast cancer therapy

1384- BBR,    Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines
- in-vitro, PC, PANC1
TumCCA↑, inducing G1-phase arrest
ROS↑, In cells treated with 10 µM berberine, ROS production increased 2.6-fold relative to control cells
Apoptosis↑,

1382- BBR,    Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells
- in-vitro, Melanoma, SK-MEL-28
Apoptosis↑,
necrosis↑,
DNAdam↑, increase in the DNA damage index
TumCCA↑, G1/G0 phase
ROS↑, The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels
Casp3↑,
p‑P53↑,
ERK↑, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls.

1381- BBR,  Rad,    Berberine enhances the sensitivity of radiotherapy in ovarian cancer cell line (SKOV-3)
- in-vitro, Ovarian, SKOV3
RadioS↑, berberine might be a capable radiosensitizer for treating SKOV-3, because of oxidative DNA damage
ROS↑,
GSH↓, decreased level of (GSH) content supported the elevated ROS generation data
Apoptosis↑,

1380- BBR,  doxoR,    treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.
- in-vivo, Nor, NA
*ROS↓, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts.
*MDA↓, Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs.
*SOD↑,
*NRF2↑,
*HO-1↑,

1379- BBR,    Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells
- in-vitro, lymphoma, NA
TumCP↓,
CDK4↓,
CDK6↓,
cycD1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

1377- BBR,    Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway
- in-vitro, Arthritis, NA
Apoptosis↑, 30 μmol/L
MMP↓,
Bax:Bcl2↑,
LC3‑Ⅱ/LC3‑Ⅰ↓, Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01)
p62↑,
*ROS↓,

1389- BBR,  Lap,    Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS
- in-vitro, BC, BT474 - in-vitro, BC, AU-565
ChemoSen↑, combination therapy of berberine with lapatinib overcame lapatinib resistance.
Apoptosis↑,
ROS↑,
NRF2↓, Berberine reverses lapatinib resistance by inhibiting the Nrf2 signaling pathway

1375- BBR,    13-[CH2CO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein
- in-vitro, CRC, HCT8 - in-vivo, NA, NA
ROS↑,
TumCP↓, 2-5X lower IC50 than normal BBR
XIAP↓,
TumCG↓,
*toxicity↓, 13-Cys-BBR Had No Kidney And Liver Toxicity

1374- BBR,  PDT,    Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells
- in-vitro, RCC, 786-O - in-vitro, RCC, HK-2
ROS↑,
TumAuto↑,
Apoptosis↑,
Casp3↑,
eff↑, HK-2 treated with BBR associated with PDT showed a significant decrease in the cellular viability compared to the control cells

1299- BBR,    Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review
- Review, NA, NA
TumCCA↑, G1 phase, G0/G1 phase, or G2/M phase
TP53↑,
COX2↓,
Bax:Bcl2↑,
ROS↑,
VEGFR2↓,
Akt↓,
ERK↓,
MMP2↓, Berberine also decreased MMP-2, MMP-9, E-cadherin, EGF, bFGF, and fibronectin in the breast cancer cells.
MMP9↓,
IL8↑,
P21↑,
p27↑,
E-cadherin↓,
Fibronectin↓,
cMyc↓, The results indicated that these derivatives could selectively induce and stabilize the formation of the c-myc in the parallel molecular G-quadruplex. Accordingly, transcription of c-myc was down-regulated in the cancer cell line

1399- BBR,  Rad,    Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review
- Review, NA, NA
*ROS↓, normal cells
*MDA↓, normal cells
*TNF-α↓, normal cells
*TGF-β↓, TGF-β1 normal cells
*IL10↑, normal cells
ROS↑, cancer cells
DNAdam↑, cancer cells
mtDam↑, cancer cells
MMP↓, cancer cells
Apoptosis↑, cancer cells
TumCCA↑, cancer cells
Hif1a↓, cancer cells
VEGF↓, cancer cells
RadioS↑, revealed radiosensitizing properties

2023- BBR,    Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor
- in-vitro, Colon, NA - in-vitro, Nor, YAMC
TumCD↑, Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells.
*toxicity↓, In contrast, YAMC(normal) cells were not sensitive to berberine-induced cell death. less cytotoxic effects on normal colon epithelial cells.
selectivity↑, see figure 2
ROS↑, berberine-stimulated ROS production
*ROS∅, ROS production in a concentration-dependent manner only in IMCE cells, but not in YAMC cells. In YAMC cells, berberine did not induce ROS production
MMP↓, berberine induced mitochondrial depolarization in a concentration-dependent manner in IMCE cells, but not in YAMC cells
*MMP∅, but not in YAMC cells
PARP↑, Berberine Activation of PARP
BioAv↝, absorption of berberine by YAMC is lower than that by IMCE cells

2021- BBR,    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways
- Review, NA, NA
*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc

1405- BBR,  Chit,    Chitosan/alginate nanogel potentiate berberine uptake and enhance oxidative stress mediated apoptotic cell death in HepG2 cells
- in-vitro, Liver, HepG2
*BioAv↑, we reported to develop a hydrophilic nanogel (NG) composed of Chitosan (Chi) and sodium alginate (Alg) using the ion gelation method for delivering Berberine hydrochloride (BBR),
ROS↑,
MMP↓,
TumCP↓,

1404- BBR,    Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation
- in-vitro, Pca, PC3
Apoptosis↑,
*Apoptosis∅, not seen in non-neoplastic human prostate epithelial cells (PWR-1E)
MMP↓,
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
ROS↑,
eff↓, Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells.
Cyt‑c↑, release of cytochrome c

1402- BBR,    Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction
- in-vitro, GBM, T98G
tumCV↓,
ROS↑,
Ca+2↑,
ER Stress↑,
eff↓, administration of the antioxidants, N-acetylcysteine and glutathione, reversed berberine-induced apoptosis
Bax:Bcl2↑,
MMP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑,

1401- BBR,    Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity
- in-vitro, GBM, U87MG
TumCP↓, 25 µM of 24 h
Apoptosis↑,
ROS↑, BBR (25 μM/24 h) increased oxidative stress in U87MG cells

1400- BBR,    Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells
- in-vitro, Melanoma, U266
ROS↑,
TumCCA↑, G2/M phase arrest
Apoptosis↑,
miR-21↓,
Bcl-2↓,
NF-kB↓, 80 μmol/L
Set9↑, 2 fold

1398- BBR,    Berberine inhibits the progression of renal cell carcinoma cells by regulating reactive oxygen species generation and inducing DNA damage
- in-vitro, Kidney, NA
TumCP↓,
TumCMig↓,
ROS↑,
Apoptosis↑,
BAX↑,
BAD↑,
Bak↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp9↑,
E-cadherin↑,
TIMP1↑,
γH2AX↑,
Bcl-2↓,
N-cadherin↓,
Vim↓,
Snail↓,
RAD51↓,
PCNA↓,

1397- BBR,  Chemo,    Effects of Coptis extract combined with chemotherapeutic agents on ROS production, multidrug resistance, and cell growth in A549 human lung cancer cells
- in-vitro, Lung, A549
TumCG↓,
ROS↑, COP and BER increased ROS production and reduced MDR in A549 cells.
MDR1↓, reduce MDR

1396- BBR,    Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro
- in-vitro, GC, SNU1041 - in-vitro, GC, SNU5
tumCV↓,
ROS↑,
MMP1↓, berberine induced downregulation of MMP-1 -2, and -9 but did not affect the level of MMP-7
MMP2↓,
MMP9↓,
MMP7∅,

1395- BBR,    Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation
- in-vitro, GC, NA
Apoptosis↑,
ROS↑,
MMP↓,
ATP↓,
AMPK↑,
TP53↑,
p‑MAPK↓, decreased phosphorylated-MAPK3/1 expression
p‑ERK↓,

1394- BBR,  DL,    Synergistic Inhibitory Effect of Berberine and d-Limonene on Human Gastric Carcinoma Cell Line MGC803
- in-vitro, GC, MGC803
eff↑, Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect
ROS↑,
MMP↓,
Casp3↑,
Bcl-2↓,
TumCCA↑,

1393- BBR,  EPI,    Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest
- in-vitro, Bladder, T24
ChemoSen↑, Ber enhanced the inhibitory effect of EPI on the viability of T24 cells
TumCCA↑, cycle arrest at G0/G1
Apoptosis↑,
cl‑Casp3↑,
cl‑Casp9↑,
BAX↑,
P53↑,
P21↑,
Bcl-2↓,
ROS↑, Ber significantly increased ROS production

1392- BBR,    Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress
- in-vitro, GC, AGS - in-vitro, GC, MKN45
TumCG↓,
TumCMig↓,
ROS↑, intracellular
MDA↑, intracellular
SOD↓, intracellular
NRF2↓,
HO-1↓,
Hif1a↓,
EMT↓,
Snail↓,
Vim↓,

1390- BBR,  Rad,    Berberine Inhibited Radioresistant Effects and Enhanced Anti-Tumor Effects in the Irradiated-Human Prostate Cancer Cells
- in-vitro, Pca, PC3
RadioS↑, cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone
Apoptosis↑,
ROS↑, ROS generation was elevated by berberine with or without irradiation.
eff↑, antioxidant NAC inhibited berberine and radiation-induced cell death.
BAX↑,
Casp3↑,
P53↑,
p38↑,
JNK↑,
Bcl-2↓,
ERK↓,
HO-1↓,

1383- CUR,  BBR,  RES,    Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases
- Review, NA, NA
GSK‐3β↝,
ROS↑, BBB increased ROS production by decreasing c-MYC expression

1391- RES,  BBR,    Effects of Resveratrol, Berberine and Their Combinations on Reactive Oxygen Species, Survival and Apoptosis in Human Squamous Carcinoma (SCC-25) Cells
- in-vitro, Tong, SCC25
ROS↑,
eff↑, cytotoxicity of the compounds was significantly improved after their combined application Additive effects were observed for doses lower than the calculated IC50 of berberine [IC50=23µg/ml] and resveratrol [IC50=9µg/ml].

1403- SDT,  BBR,    From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells
- in-vitro, Cerv, HeLa - in-vitro, Lung, LLC1
eff↑, revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability
tumCV↓,
ATP↓,
ROS↑,
Casp3↑,
Casp7↑,
mtDam↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 42

Results for Effect on Cancer/Diseased Cells:
AIF↝,1,   Akt↓,4,   AMPK↑,3,   angioG↓,1,   AntiCan↑,1,   AntiTum↑,1,   AP-1↓,1,   Apoptosis↑,19,   AR↓,1,   ATM↑,1,   ATP↓,4,   BAD↑,1,   Bak↑,1,   BAX↑,6,   Bax:Bcl2↑,4,   Bcl-2↓,8,   Bcl-xL↓,1,   BioAv↓,3,   BioAv↝,1,   Ca+2↑,2,   Casp↑,1,   Casp3↓,1,   Casp3↑,7,   cl‑Casp3↑,4,   Casp7↑,1,   Casp8↑,1,   Casp9↑,3,   cl‑Casp9↑,3,   CCR7↓,1,   CD133↓,1,   CD4+↓,1,   CDC25↓,2,   CDK2↓,1,   CDK4↓,2,   CDK6↓,1,   ChemoSen↓,1,   ChemoSen↑,4,   CHOP↓,1,   CHOP↑,1,   cMyc↓,2,   COX2↓,5,   COX2↑,1,   CSCs↓,1,   CXCR4↓,1,   CycB↓,1,   cycD1↓,2,   cycE↓,1,   Cyt‑c↑,4,   Diff↓,1,   DNAdam↑,3,   DNMT1↓,1,   Dose?,1,   Dose↓,1,   Dose↑,1,   E-cadherin↓,1,   E-cadherin↑,1,   eff↓,4,   eff↑,12,   eff↝,1,   EGFR↓,2,   EMT↓,2,   EMT↑,1,   ER Stress↑,3,   ERK↓,5,   ERK↑,1,   p‑ERK↓,1,   FAK↓,1,   Fas↑,1,   FasL↑,1,   Fibronectin↓,1,   Glycolysis↓,1,   GSH↓,1,   GSK‐3β↝,1,   ac‑H3↑,1,   ac‑H4↑,1,   HDAC↓,1,   Hif1a↓,3,   HO-1↓,2,   IAP1↓,1,   ICD↑,1,   IL1↓,1,   IL6↓,2,   IL8↑,1,   Inflam↓,2,   JAK2↓,1,   JNK↑,3,   LC3‑Ⅱ/LC3‑Ⅰ↓,1,   LC3B↑,1,   LC3II↑,1,   LC3s↑,1,   MAPK↓,1,   p‑MAPK↓,1,   MCP1↓,2,   MDA↑,1,   MDM2↓,1,   MDR1↓,1,   MEK↓,1,   miR-21↓,1,   MMP↓,13,   MMP1↓,2,   MMP13↓,1,   MMP2↓,5,   MMP3↓,1,   MMP7∅,1,   MMP9↓,5,   mtDam↑,3,   mTOR↓,3,   p‑mTORC1↓,1,   N-cadherin↓,1,   n-MYC↓,1,   necrosis↑,1,   Nestin↓,1,   NF-kB↓,4,   NOTCH↓,1,   NQO1↓,1,   NRF2↓,3,   NRF2↑,1,   OS↑,1,   other↓,1,   P21↑,3,   p27↑,2,   p38↑,1,   P53↑,4,   p‑P53↑,1,   p62↑,1,   PARP↑,1,   cl‑PARP↑,2,   PCNA↓,1,   PERK↓,1,   PGE2↓,3,   PI3K↓,3,   PTEN↑,1,   RAD51↓,1,   RadioS↑,5,   Raf↓,1,   RAS↓,1,   RB1↑,1,   RenoP↑,1,   Rho↓,1,   ROCK1↓,1,   ROS↑,36,   p‑S6K↓,1,   selectivity↑,4,   Set9↑,1,   Snail↓,2,   SOD↓,1,   SOX2↓,1,   STAT3↓,2,   survivin↓,1,   Telomerase↓,2,   TGF-β↓,1,   TIMP1↑,1,   TNF-α↓,2,   TP53↑,2,   TumAuto↑,2,   TumCCA↑,13,   TumCD↑,2,   TumCG↓,4,   TumCI↓,1,   TumCMig↓,2,   TumCP↓,6,   TumCP↑,1,   tumCV↓,4,   TumMeta↓,1,   uPA↓,2,   VEGF↓,3,   VEGFR2↓,2,   Vim↓,2,   Wnt↓,1,   XIAP↓,2,   β-catenin/ZEB1↓,1,   γH2AX↑,1,  
Total Targets: 172

Results for Effect on Normal Cells:
ALAT↓,1,   ALP↓,1,   AMPK↑,1,   antiOx?,1,   antiOx↑,1,   Apoptosis∅,1,   AST↓,1,   ATF4↓,1,   BAX↓,1,   Beclin-1↑,1,   BG↓,1,   BioAv↑,1,   Ca+2↓,1,   cardioP↑,1,   cl‑Casp3↓,1,   Catalase↑,2,   CHOP↓,1,   cognitive↑,1,   DNAdam↓,1,   Dose↝,1,   eff↑,1,   eIF2α↓,1,   p‑eIF2α↓,1,   ER Stress↓,3,   GPx↑,2,   GSH↑,1,   hepatoP↑,1,   HO-1↑,1,   IL10↑,2,   IL6↓,1,   Inflam↓,2,   JAK2↑,1,   JNK↓,1,   LC3II↑,1,   lipid-P↓,1,   MDA↓,2,   MMP∅,1,   mTOR↑,1,   neuroP↑,2,   NRF2↑,1,   p‑PERK↓,1,   ROS↓,8,   ROS∅,1,   SOD↑,3,   STAT3↑,1,   TGF-β↓,1,   TNF-α↓,2,   toxicity↓,2,   UPR↓,1,  
Total Targets: 49

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
42 Berberine
3 Photodynamic Therapy
3 Radiotherapy/Radiation
2 Resveratrol
1 immunotherapy
1 5-fluorouracil
1 doxorubicin
1 Lapatinib
1 chitosan
1 Chemotherapy
1 D-limonene
1 epirubicin
1 Curcumin
1 SonoDynamic Therapy UltraSound
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:41  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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