condition found tbRes List
CUR, Curcumin: Click to Expand ⟱
Features:
Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells.
- GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown

Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓">ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- 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⟱
3446- ALA,  CUR,    The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression
- in-vivo, Nor, NA
*hepatoP↑, Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.
*α-SMA↓, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication
*COL3A1↓,
*ROS↓, scavenging activity to ROS and a capacity to regenerate endogenous antioxidants such as GSH, and vitamins C and E.
*GSH↑,
*ALAT↓, ALT, AST, and ALP activity levels compared to those of the control group. The use of NACS, Curc, and/or Lip acid significantly reduced the toxic effects of NHPA on those enzymes,
*AST↓,
*ALP↓,
*MDA↓, The combination therapy showed an apparent reduction in MDA level more than other treatments

3514- Bor,  CUR,    Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta
- in-vivo, AD, NA
*DNAdam↓, Co-administration of BA and curcumin on synaptosomes exposed to Aβ1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities.
*MDA↓,
*AChE↓,
*neuroP↑, BA and curcumin had protective effects on rat brain synaptosomes against Aβ1-42 exposure.
*ROS↓, BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of Aβ1-42 exposed.
*NO↓, Synaptosomes treated with BA showed a significant reduction in MDA and NO levels

462- CUR,    Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress
- in-vitro, Pca, PC3
Bcl-2↓,
MMP↓,
cl‑Casp3↑,
BAX↑,
BIM↑,
p‑PARP↑,
PUMA↑,
p‑P53↑,
ROS↑,
p‑ERK↑,
p‑eIF2α↑,
CHOP↑,
ATF4↑,

477- CUR,    Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells
- in-vitro, Cerv, SiHa
TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

440- CUR,    Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells
- vitro+vivo, CRC, SW480 - vitro+vivo, CRC, HT-29
NNMT↓,
p‑STAT3↓,
TumCP↓,
TumCCA↑, G2/M phase cell cycle arrest
ROS↑,

448- CUR,    Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation
- in-vitro, CRC, HT-29
Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

454- CUR,    Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway
- in-vitro, GC, MGC803
TumCMig↓,
TumCP↓,
ROS↑,
mtDam↑,
DNAdam↑,
Apoptosis↑,
ATR↑,
P21↑,
p‑P53↑,
GADD45A↑,
p‑γH2AX↑,

1980- CUR,  Rad,    Thioredoxin reductase-1 (TxnRd1) mediates curcumin-induced radiosensitization of squamous carcinoma cells
- in-vitro, Cerv, HeLa - in-vitro, Laryn, FaDu
selectivity↑, previously demonstrated that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxic effects of radiation on normal human fibroblasts
RadioS↑,
TrxR↓, inhibitory activity of curcumin on the anti-oxidant enzyme Thioredoxin Reductase-1 (TxnRd1) is required for curcumin-mediated radiosensitization of squamous carcinoma cells
ROS↑, induced reactive oxygen species
ERK↑, sustained ERK1/2 activation
Dose∅, Curcumin treatment resulted in a dose-dependent decrease in TxnRd activity with an IC50 of approximately 10 µM in both cell lines
cl‑PARP↑, curcumin induced a robust increase in cleaved PARP

1510- CUR,  Chemo,    Combination therapy in combating cancer
- Review, NA, NA
*NRF2↑, Curcuminoids are linear diarylheptanoids that upregulate Nrf2 expression and induce Nrf2 translocation to the nucleus to elicit its antioxidant effects
*GSH↑, curcuminoids upregulate glutathione levels which have been shown to reduce ROS levels and remove carcinogens, aiding in chemoprevention
*ROS↓,
ChemoSideEff↓, aiding in chemoprevention
eff↑, Curcuminoids in combination with chemotherapy have demonstrated an overall positive outcome, and have also shown to increase the survival rate in some patients
OS↓, shown to increase the survival rate in some patients
chemoP↑, have been shown to reduce ROS levels and remove carcinogens, aiding in chemoprevention

1609- CUR,  EA,    Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells
- in-vitro, Cerv, NA
eff↑, combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay
Dose∅, IC50 value for Curcumin is calculated as 16.52 mM and for Ellagic acid the IC50 Value is 19.47 mM. The combination of Curcumin and Ellagic acid has IC50 value 10.9 mM.
ROS↑, Curcumin alone increases the ROS level significantly. Similarly the C + E treated cells exhibited a very high magnitude of ROS level.
DNAdam↑, Curcumin and Ellagic acid show mild degree of DNA damage at this concentration but the C + E treated cells shows greater degree of DNA damage
P53↑, C + E treated cells show greater degree of stabilization of p53
P21↑, Elevated expression of p21 in response to Curcumin and C + E treatment
BAX↑, But the C + E treated cells showed higher expression of Bax
Dose∅, Curcumin daily shows detectable levels of Curcumin in plasma and urine and the concentration is close to 11.1 nMol/l

1978- CUR,    Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells
- in-vitro, Cerv, HeLa
TrxR1↓, curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells
ROS↑,
DNA-PK↑, subsequently induces DNA oxidative damage
eff↑, curcumin-pretreated HeLa cells are more sensitive to oxidative stress
Trx↓, down-regulates Trx1 level and decreases Trx activity in HeLa cells
Trx1↓,

1979- CUR,  Rad,    Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase
- in-vitro, Lung, A549
eff↑, As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay.
ROS↑, significant increase in cellular ROS
GSH/GSSG↓, decrease in GSH to GSSG ratio
TrxR↓, inhibition of thioredoxin reductase enzyme by DIMC
selectivity↑, DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system.

1981- CUR,    Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity
- in-vitro, Lung, NA
eff↑, Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin
ROS↑, Mitocurcumin increased the mitochondrial reactive oxygen species (ROS
mt-GSH↓, decreased the mitochondrial glutathione levels
Bax:Bcl2↑, increased BAX to BCL-2 ratio
Cyt‑c↑, cytochrome C release into the cytosol
MMP↓, loss of mitochondrial membrane potential
Casp3↑, increased caspase-3 activity
Trx2↓, mitocurcumin revealed that it binds to the active site of the mitochondrial thioredoxin reductase (TrxR2) with high affinity
TrxR↓, In corroboration with the above finding, mitocurcumin decreased TrxR activity in cell free as well as the cellular system.
mt-DNAdam↑, mitochondrial DNA damage

2308- CUR,    Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells
- in-vitro, Liver, HepG2
GlucoseCon↓, Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production
lactateProd↓,
ECAR↓,
NO↓,
ROS↑, Curcumin favors the ROS production in HepG2 cells in normal as well as hyperglycemic conditions. ROS production was detected in cancer cells treated with curcumin, or doxorubicin, or their combinations in NG or HG medium for 24 h
HK2↓, HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, tr
PFK1↓,
GAPDH↓,
PKM2↓,
LDHA↓,
FASN↓,
GLUT1↓, Curcumin treatment was able to significantly decrease the expression of GLUT1, HKII, and HIF-1α in HepG2 cells either incubated in NG or HG medium.
MCT1↓,
MCT4↓,
HCAR1↓,
SDH↑, Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition
ChemoSen↑, Curcumin Prevents High Glucose-Induced Chemoresistance
ROS↑, Treatment of cells with doxorubicin in presence of curcumin was found to cooperatively augment the ROS level in cells of both NG and HG groups.
BioAv↑, Curcumin Favors Drug Accumulation in Cancer Cells
P53↑, An increased expression of p53 in curcumin-treated cells can be suggestive of susceptibility towards cytotoxic action of anticancer drugs
NF-kB↓, curcumin has therapeutic benefits in hyperglycemia-associated pathological manifestations and through NF-κB inhibition
pH↑, Curcumin treatment was found to resist the lowering of pH of culture supernatant both in NG as well in HG medium.

2312- CUR,    Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy
- Review, Var, NA
ROS↑,
PKM2↓, ROS accumulation inhibits PKM2

2654- CUR,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, ROS induction has been implicated as one of the mechanisms of the anticancer activity of curcumin and its derivatives in various cancers
Catalase↓, Curcumin induces ROS by inhibiting the activity of various ROS-related metabolic enzymes, such as CAT, SOD1, glyoxalase 1, and NAD(P)H dehydrogenase [quinone] 1 [146,149]
SOD1↓,
GLO-I↓,
NADPH↓,
TumCCA↑, ROS accumulation further mediates G1 or G2/M cell cycle arrest [146,147,150,154], senescence [146], and apoptosis.
Apoptosis↑,
Akt↓, downregulation of AKT phosphorylation [145
ER Stress↑, endoplasmic reticulum stress (namely through the PERK–ATF4–CHOP axis)
JNK↑, activation of the JNK pathway [151],
STAT3↓, and inhibition of STAT3 [155].
BioAv↑, Additionally, the combination of curcumin and piperine, a pro-oxidative phytochemical that drastically increases the bioavailability of curcumin in humans

872- CUR,  RES,    New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects
- in-vitro, BC, TUBO - in-vitro, BC, SALTO
TumCP↓,
tumCV↓,
p62↓, reduced by Cur
p62↑, accumulated by Res
TumAuto↑, Cur only
TumAuto↓, Res only
ROS↑, increased ROS with Res
ROS↓, decreased ROS with Cur or combination
CHOP↑, strongly upregulated by the curcumin/resveratrol combination

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

1408- CUR,    Antiproliferative and ROS Regulation Activity of Photoluminescent Curcumin-Derived Nanodots
- in-vitro, Lung, A549
ROS↓, antioxidation activity at low concentrations (<0.08 mg/mL) with low levels of reactive oxygen species (ROS) generation, i.e., 82% of the ROS level in cells without treatment for A549 cells;
ROS↑, at high concentrations, the nanodots exhibit a pro-oxidant effect on both the cancer cells (A549) and normal cells (EA.hy926) by inducing more ROS generation and dose-dependent cytotoxicity.

1409- CUR,    Curcumin analog WZ26 induces ROS and cell death via inhibition of STAT3 in cholangiocarcinoma
- in-vivo, CCA, Walker256
TumCG↓,
ROS↑,
MMP↓,
STAT3↓,
TumCCA↑, G2/M cell cycle
eff↓, Pretreatment of N-acetyl cysteine (NAC), an antioxidant agent, could fully reverse the WZ26-induced ROS-mediated changes in CCA cells

1410- CUR,    Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway
- vitro+vivo, OS, MG63
tumCV↓,
Apoptosis↑,
TumCG↓,
NRF2↓, after treatment with curcumin, Nrf2 and GPX4 levels were significantly decreased
GPx4↓,
HO-1↓,
xCT↓, SLC7A11
ROS↑, our results revealed that after treatment with curcumin, ROS and MDA levels were significantly increased while GSH levels were decreased
MDA↑,
GSH↓,

1411- CUR,  Cisplatin,    Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects
- Review, Var, NA
ChemoSen↑, decreasing CP's adverse impacts and improving its antitumor
*ROS↓, Curcumin administration reduces ROS levels to prevent apoptosis in normal cells.
*NF-kB↓, curcumin can inhibit inflammation via down-regulation of NF-κB to maintain the normal function of organs.
TumCCA↑,

1418- CUR,    Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis
- Review, Arthritis, NA
*COX2↓, Curcumin downregulates the cyclooxygenase-2 (COX-2) pathway, reducing the production of prostaglandins associated with inflammation
*Inflam↓,
*5LO↓, directly inhibits lipoxygenase (LOX)
*NO↓,
*NF-kB↓,
*TNF-α↓,
*IL1↓,
*IL2↑,
*IL6↓,
*IL8↓,
*IL12↓,
*MCP1↓,
*PGE2↓,
*MMP2↓,
*MMP3↓,
*MMP9↓,
*NLRP3↓,
*ROS↓, arthritis(basically normal cell)

1485- CUR,  Chemo,  Rad,    Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs
- Review, Var, NA
ChemoSen↑, Such effects of curcumin were due to its ability to sensitize cancer cells for increased production of ROS
NF-kB↓, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt
*STAT3↓, curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-kB, STAT3, COX2, Akt,
*COX2↓,
*Akt↓,
*NRF2↑, The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase
*HO-1↑,
*GPx↑,
*NADPH↑,
*GSH↑, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase)
*ROS↓, dietary curcumin can inhibit chemotherapy-induced apoptosis via inhibition of ROS generation and blocking JNK signaling
*p300↓, inhibit p300 HAT activity
radioP↑, radioprotector for normal organs
chemoP↑, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity.
RadioS↑,

132- CUR,    Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells
- in-vitro, Pca, NA
TumCCA↑,
ROS↑,
TumAuto↑,
UPR↑,

134- CUR,  RES,  MEL,  SIL,    Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
Apoptosis↑,
ROS↑,
Trx1↓,

140- CUR,    Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling
- in-vitro, Pca, PC3
CAFs/TAFs↓,
EMT↓,
ROS↓, We found that curcumin abolished the CAF-derived CM-induced ROS production and CXCR4 and IL-6 receptor expression in PC3 cells
CXCR4↓,
IL6↓,
MAOA↓,
mTOR↓,
HIF-1↓,

143- CUR,    Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ER Stress↑,
CHOP↑,
GRP78/BiP↑,
ROS↑,

159- CUR,    Crosstalk from survival to necrotic death coexists in DU-145 cells by curcumin treatment
- in-vitro, Pca, DU145
ROS↑, at higher concentrations
p‑Jun↑, phosphorylation
p‑p38↑, phosphorylation

15- CUR,  UA,    Effects of curcumin and ursolic acid in prostate cancer: A systematic review
NF-kB↝,
Akt↝,
AR↝,
Apoptosis↝,
Bcl-2↝,
Casp3↝,
BAX↝,
P21↝,
ROS↝,
Apoptosis↝,
Bcl-xL↝,
JNK↝,
MMP2↝,
P53↝,
PSA↝,
VEGF↝,
COX2↝,
cycD1↝,
EGFR↝,
IL6↝,
β-catenin/ZEB1↝,
mTOR↝,
NRF2↝,
p‑Akt↝,
AP-1↝,
Cyt‑c↝,
PI3K↝,
PTEN↝,
Cyc↝,
TNF-α↝,

117- CUR,    Increased Intracellular Reactive Oxygen Species Mediates the Anti-Cancer Effects of WZ35 via Activating Mitochondrial Apoptosis Pathway in Prostate Cancer Cells
- in-vivo, Pca, RM-1 - in-vivo, Pca, DU145
ROS↑,

118- CUR,    Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
ROS↑,
Bcl-2↓,
PARP↑,
cDC2↓,
CycB↓,
MDM2↓,

407- CUR,    Curcumin inhibited growth of human melanoma A375 cells via inciting oxidative stress
- in-vitro, Melanoma, A375
Apoptosis↑,
ROS↑,
GSH↓,
MMP↓, wreaking

410- CUR,    Nrf2 depletion enhanced curcumin therapy effect in gastric cancer by inducing the excessive accumulation of ROS
- vitro+vivo, GC, AGS - vitro+vivo, GC, HGC27
ROS↑,
NRF2↑, add knockdown of NRF2 enchances CUR efficacy

412- CUR,    Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
ROS↑, 25uM
PTP1B↓,

414- CUR,    Transcriptome Investigation and In Vitro Verification of Curcumin-Induced HO-1 as a Feature of Ferroptosis in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Ferroptosis↑,
Iron↑,
ROS↑,
lipid-P↑,
MDA↑,
GSH↓,
HO-1↑, Curcumin upregulates a variety of ferroptosis target genes related to redox regulation, especially heme oxygenase-1 (HO-1).
NRF2↑,
GPx↓,
ROS↑,
Iron↑, curcumin caused marked accumulation of intracellular iron
GPx4↓,
HSP70/HSPA5↑,
ATFs↑, ATF4
CHOP↑, DDIT3
MDA↑,
FTL↑, Curcumin upregulated FTL (encoding ferritin light chain), FTH1
FTH1↑,
BACH1↑,
REL↑, v-rel reticuloendotheliosis viral oncogene homolog A
USF1↑,
NFE2L2↑,

424- CUR,    Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Src↓,
p‑STAT1↓, pSTAT-1
p‑Akt↓,
p‑p44↓, p-p44
p‑p42↓, p-p42
RAS↓,
Raf↓, c-RAF
Vim↓,
β-catenin/ZEB1↓,
P53↓,
Bcl-2↓,
Mcl-1↓,
PIAS-3↑,
SOCS-3↑,
SOCS1↑,
ROS↑,
NF-kB↓, NF-kB inactivation, ROS generation and PA depletion in MCF-7, MDA-MB-453 and MDA-MB-231 breast can- cer cells
PAO↑,
SSAT↑,
P21↑,
Bak↑,

426- CUR,    Use of cancer chemopreventive phytochemicals as antineoplastic agents
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, CAL51
Bcl-2↓,
ROS↑,
BAX↑,
RAD51↑,
γH2AX↑,

405- CUR,  5-FU,    Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis
- vitro+vivo, CRC, HCT116
Apoptosis↑, more pronounced increase in apoptosis in p53-deficient when compared to p53-proficient cells
TumCMig↓,
NRF2↑,
ROS↑, antioxidant N-acetylcysteine suppressed the induction of apoptosis by curcumin
MET↓,
NA↑,

3576- CUR,    Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease
- Review, AD, NA
*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

2688- CUR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Var, NA - Review, AD, NA
*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↓,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

3575- CUR,    The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
- in-vivo, AD, NA
*antiOx↓, potent polyphenolic antioxidant
*ROS↓, Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1β, a proinflammatory cytokine elevated in the brains of these mice.
*IL1β↓,
*Aβ↓, low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble β-amyloid (Aβ), soluble Aβ, and plaque burden were significantly decreased by 43–50%
*Inflam↓, we report that the Indian spice curcumin suppresses indices of inflammation and oxidative damage in the brains of APPSw mice, factors that have been implicated in AD pathogenesis.
*toxicity↓, Studies have consistently shown that curcumin is relatively nontoxic and has few side effects at doses greater than the low dose tested in our mice.

3574- CUR,    The effect of curcumin (turmeric) on Alzheimer's disease: An overview
- Review, AD, NA
*antiOx↑, Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD
*Inflam↓,
*lipid-P↓,
*cognitive↑,
*memory↑, overall memory in patients with AD has improved.
*Aβ↓, curcumin may help the macrophages to clear the amyloid plaques found in Alzheimer's disease.
*COX2↓, Curcumin is found to inhibit cyclooxygenase (COX-2),
*ROS↓, The reduction of the release of ROS by stimulated neutrophils, inhibition of AP-1 and NF-Kappa B inhibit the activation of the pro-inflammatory cytokines TNF (tumor necrosis factor)-alpha and IL (interleukin)-1 beta
*AP-1↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*SOD↑, It also increased the activity of superoxide dismutase, sodium-potassium ATPase that normally decreased with aging.
*GSH↑, followed by a significant elevation in oxidized glutathione content.
*HO-1↑, curcumin induces hemoxygenase activity.
*IronCh↑, curcumin effectively binds to copper, zinc and iron.
*BioAv↓, Curcumin has poor bioavailability. Because curcumin readily conjugated in the intestine and liver to form curcumin glucuronides.
*Half-Life↝, , serum curcumin concentrations peaked one to two hours after an oral dose
*Dose↝, Peak serum concentrations were 0.5, 0.6 and 1.8 micromoles/L at doses of 4, 6 and 8 g/day respectively.
*BBB↑, Curcumin crosses the blood brain barrier and is detected in CSF
*BioAv↑, Absorption appears to be better with food.
*toxicity∅, A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for three months found no toxicity from curcumin.
*eff↑, Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increase the bioavailablity of curcumin by 2000%

2980- CUR,    Inhibition of NF B and Pancreatic Cancer Cell and Tumor Growth by Curcumin Is Dependent on Specificity Protein Down-regulation
- in-vivo, PC, NA
TumCG↓, curcumin inhibits Panc28 and L3.6pL pancreatic cancer cell and tumor growth in nude mice bearing L3.6pL cells as xenografts
p50↓, curcumin decreased expression of p50 and p65 proteins and NFkappaB-dependent transactivation and also decreased Sp1, Sp3, and Sp4 transcription factor
p65↓,
NF-kB↓,
Sp1/3/4↓,
MMP↓, Curcumin also decreased mitochondrial membrane potential and induced reactive oxygen species in pancreatic cancer cell
ROS↑,

2978- CUR,    N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells
- in-vitro, Lung, A549
ROS↑, ROS induced by curcumin in A549 cells was detected by flow cytometry
hTERT↓, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin
Sp1/3/4↓, curcumin decreases the expression of Sp1 through proteasome pathway
eff↓, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin.

2821- CUR,    Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)
- Review, Var, NA
*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,

2820- CUR,    Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways
- in-vitro, HCC, HepG2
*hepatoP↑, Curcumin also significantly reduced oxidative stress in liver, inhibited apoptosis, and induced autophagy. In vitro, curcumin (50 μM) decreased HepG2 cells viability and the concentration of SQSTM1.
*ROS?,
tumCV↓,

2819- CUR,  Chemo,    Curcumin as a hepatoprotective agent against chemotherapy-induced liver injury
- Review, Var, NA
*hepatoP↑, Several studies have shown that curcumin could prevent and/or palliate chemotherapy-induced liver injury
*Inflam↓, mainly due to its anti-inflammatory, antioxidant, antifibrotic and hypolipidemic properties.
*antiOx↓,
*lipid-P↓, Curcumin can lower lipid peroxidation by increasing the content of GSH, a major endogenous antioxidant,
*GSH↑,
*SOD↑, as well as by enhancing the activity of endogenous antioxidant enzymes, such as SOD, CAT, GPx and GST
*Catalase↑,
*GPx↑,
*GSTs↑,
*ROS↓, elimination of ROS
*ALAT↓, attenuated the increase in serum levels of TNF-α as well as several liver enzymes, including ALT, AST, alkaline phosphatase and MDA which are markers of liver damage caused by MTX or cisplatin.
*AST↓,
*MDA↓,
*NRF2↑, Curcumin also attenuated DILI through activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway
*COX2↑, Curcumin can also inhibit the expression of cyclooxygenase-2 (COX-2)
*NF-kB↓, NF-κB inhibition, which decreased the downstream induction of COX-2, ICAM-1 and MCP-1 pro-inflammatory regulators
*ICAM-1↓,
*MCP1↓,
*HO-1↑, increase in HO-1 and NQO1 expression
CXCc↓, Downregulation of pro-inflammatory chemokines, (CXCL1, CXCL2, and MCP-1)

2818- CUR,    Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/ GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways
- Review, AD, NA
*neuroP↑, Curcumin's protective functions against neural cell degeneration due to mitochondrial dysfunction and consequent events such as oxidative stress, inflammation, and apoptosis in neural cells have been documented
*ROS↓, studies show that curcumin exerts neuroprotective effects on oxidative stress.
*Inflam↓,
*Apoptosis↓,
*cognitive↑, cognitive performance to receive the title of neuroprotective
*cardioP↑, Studies have shown that curcumin can induce cell regeneration and defense in multiple organs such as the brain, cardiovascular system,
other↑, It has been shown that chronic use of curcumin in patients with neurodegenerative disorder can cause gray matter volume increase
*COX2↓, Curcumin also decreased the brain protein levels and activity of cyclooxygenase 2 (COX-2)
*IL1β↓, inhibition of IL-1β and TNF-α production, and enhancement of Nf-Kβ inhibition
*TNF-α↓,
NF-kB↓,
*PGE2↓, hronic curcumin therapy has shown a significant decrease in lipopolysaccharide (LPS)-induced elevation of brain prostaglandin E2 (PGE2) synthesis in rats
*iNOS↓, curcumin pretreatment decreased NOS activity in the ischemic rat model
*NO↓, curcumin has been shown to decrease NOS expression and NO production in rat brain tissue
*IL2↓, IL-2 is a cytokine that is anti-inflammatory. Numerous studies have shown that curcumin increases the secretion of IL-2
*IL4↓, curcumin reduced levels of IL-4
*IL6↓, Numerous studies have shown that curcumin in neurodegenerative events attenuates IL-6 production
*INF-γ↓, curcumin reduced the production of INF-γ, as pro-inflammatory cytokine
*GSK‐3β↓, Furthermore, previous findings have confirmed that inhibition of GSK-3β or CREB activation by curcumin has reduced the production of pro-inflammatory mediators under different conditions
*STAT↓, Inhibition of GSK-3β by curcumin has been found to result in reduced STAT activation
*GSH↑, chronic curcumin therapy increased glutathione levels in primary cultivated rat cerebral cortical cells
*MDA↓, multiple doses of 5, 10, 40 and 60 mg/kg) in rodents will inhibit neurodegenerative agent malicious effects, and reduce the amount of MDA and lipid peroxidation in brain tissue
*lipid-P↓,
*SOD↑, Curcumin induces increased production of SOD, glutathione peroxidase (GPx), CAT, and glutathione reductase (GR) activating antioxidant defenses
*GPx↑,
*Catalase↑,
*GSR↓,
*LDH↓, Curcumin decreased lactate dehydrogenase, lipoid peroxidation, ROS, H2O2 and inhibited Caspase 3 and 9
*H2O2↓,
*Casp3↓,
*Casp9↓,
*NRF2↑, ncreased mitochondrial uncoupling protein 2 and increased mitochondrial biogenesis. Nuclear factor-erythroid 2-related factor 2 (Nrf2)
*AIF↓, Curcumin treatment decreased the number of AIF positive nuclei 24 h after treatment in the hippocampus,
*ATP↑, curcumin in hippocampal cells induced an increase in mitochondrial mass leading to increased production of ATP with major improvements in mitochondrial efficiency

2816- CUR,    NEUROPROTECTIVE EFFECTS OF CURCUMIN
- Review, AD, NA - Review, Park, NA
*neuroP↑, Curcumin has an outstanding safety profile and a number of pleiotropic actions with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and anti-protein-aggregate activities.
*Inflam↓,
*antiOx↑,
*BioAv↓, despite concerns about poor oral bioavailability, curcumin has at least 10 known neuroprotective action
*AP-1↓, Curcumin inhibition of AP-1 and NF-κB-mediated transcription occurs at relatively low (<100 nM) doses and might be due to inhibition of histone acetylase (HAT) or activation of histone deacetylase (HDAC) activity
*NF-kB↓,
*HATs↓,
*HDAC↑,
Dose↑, At high doses (>3 µM) that are relevant to colon cancer but unlikely achievable with oral delivery in plasma and tissues outside of the gut, curcumin can act as an alkylating agent,10 a phase II enzyme inducer,11 and stimulate antioxidant response el
*ROS↓, We also found that curcmin reduced oxidative damage, inflammation, and cognitive deficits in rats receiving CNS infusions of toxic Aβ
*cognitive↑,
*Aβ↓, dose-dependently blocked Aβ aggregation at submicromolar concentrations

2810- CUR,    Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials
- Review, Nor, NA
*SOD↑, significant increase of SOD activities especially for studies ≥6 weeks
*lipid-P↓, also significantly reduced lipid peroxides, increased GSH and catalase activity.
*GSH↑,
*Catalase↑,
*ROS↓, neutralization of free radicals

1998- Myr,  CUR,    Thioredoxin-dependent system. Application of inhibitors
- Review, Var, NA
TrxR↓, myricetin, which like curcumin, can cause irreversible inhibition of TrxR activity
ROS↑, Curcumin-induced alkylation of TrxR can have effects analogous to NADPH oxidase that involve significant increases in ROS production and increased oxidative stress

918- QC,  CUR,  VitC,    Anti- and pro-oxidant effects of oxidized quercetin, curcumin or curcumin-related compounds with thiols or ascorbate as measured by the induction period method
- Analysis, NA, NA
ROS↑, CUR enhances the prooxidant activity of ascorbate(vit C)
ROS↑, Under anaerobic conditions, QUE, with a catechol ring, may be more prooxidant than CUR, with a phenol ring.

103- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- vitro+vivo, BC, 4T1
ROS↑,
MMP↓,
Bcl-2↓,
BAX↑,
Casp9↑,
T-Cell↑, (CD4+CD8+)
TGF-β↓,

871- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- in-vitro, BC, 4T1 - in-vivo, BC, 4T1
T-Cell↑, in tumor microenviroment
Neut↓,
Macrophages↓,
ROS↑, RCQ significantly increased reactive oxygen species
MMP↓, in cancer cells
other↓, alleviate immunosuppression of the tumor microenvironment to enhance the anti-tumor effect.
AntiTum↑, at least nearly 5 times higher than that of a single Res/Cur/Que  = 1:1:0.5
TumVol↓, 35-47% tumor inhibition rate

119- UA,  CUR,  RES,    Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, ROS↑ only with CUR alone, otherwise ↓
p‑STAT3↓,
Src↓,
AMPK↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 56

Results for Effect on Cancer/Diseased Cells:
Akt↓,3,   Akt↑,1,   Akt↝,1,   p‑Akt↓,2,   p‑Akt↝,1,   AMPK↑,1,   AntiTum↑,1,   AP-1↝,1,   Apoptosis↑,10,   Apoptosis↝,2,   AR↝,1,   ATF4↑,1,   ATF6↑,1,   ATFs↑,1,   ATR↑,1,   BACH1↑,1,   BAD↑,1,   p‑BAD↓,1,   Bak↑,1,   BAX↑,4,   BAX↝,1,   Bax:Bcl2↑,1,   Bcl-2↓,7,   Bcl-2↝,1,   Bcl-xL↝,1,   Beclin-1↑,1,   BIM↑,1,   BioAv↓,1,   BioAv↑,3,   CAFs/TAFs↓,1,   Casp3↑,2,   Casp3↝,1,   cl‑Casp3↑,2,   Casp9↑,1,   Catalase↓,1,   cDC2↓,1,   CDC25↓,1,   chemoP↑,2,   ChemoSen↑,5,   ChemoSideEff↓,1,   CHOP↑,5,   COX2↝,1,   CSCs↓,1,   CXCc↓,1,   CXCL12↓,1,   CXCR4↓,1,   Cyc↝,1,   CycB↓,2,   cycD1↓,1,   cycD1↝,1,   Cyt‑c↑,2,   Cyt‑c↝,1,   DNA-PK↑,1,   DNAdam↑,3,   mt-DNAdam↑,1,   DNMT1↓,1,   Dose↑,1,   Dose∅,3,   ECAR↓,1,   eff↓,2,   eff↑,6,   EGFR↝,1,   p‑eIF2α↑,1,   EMT↓,2,   ER Stress↑,3,   ERK↑,1,   p‑ERK↑,2,   EZH2↓,1,   FASN↓,1,   Fenton↑,1,   Ferroptosis↑,1,   FTH1↑,1,   FTL↑,1,   GADD45A↑,1,   GAPDH↓,1,   GLO-I↓,1,   GlucoseCon↓,1,   GLUT1↓,1,   GPx↓,1,   GPx1↓,1,   GPx4↓,3,   GRP78/BiP↑,1,   GSH↓,4,   mt-GSH↓,1,   GSH/GSSG↓,1,   GSK‐3β↝,1,   HCAR1↓,1,   HIF-1↓,1,   Hif1a↓,1,   HK2↓,1,   HO-1↓,1,   HO-1↑,3,   HSP27↑,1,   HSP70/HSPA5↑,1,   hTERT↓,1,   IL6↓,2,   IL6↝,1,   Iron↑,3,   JAK2↓,1,   JNK↑,1,   JNK↝,1,   p‑JNK↑,1,   p‑Jun↑,1,   lactateProd↓,1,   LAMs↓,1,   LC3‑Ⅱ/LC3‑Ⅰ↑,1,   LC3II↓,1,   LDHA↓,1,   lipid-P↑,1,   Macrophages↓,1,   MAOA↓,1,   Mcl-1↓,1,   MCT1↓,1,   MCT4↓,1,   MDA↑,3,   MDM2↓,1,   MET↓,1,   miR-21↓,1,   miR-27a-3p↓,1,   MMP↓,7,   MMP2↓,1,   MMP2↝,1,   MMP9↓,1,   mtDam↑,2,   mTOR↓,2,   mTOR↝,1,   NA↑,1,   NADPH↓,1,   Nanog↓,1,   Neut↓,1,   NF-kB↓,6,   NF-kB↝,1,   NFE2L2↑,1,   NNMT↓,1,   NO↓,1,   NOTCH1↓,1,   NQO1↑,1,   NRF2↓,1,   NRF2↑,3,   NRF2↝,1,   OCT4↓,1,   OS↓,1,   other↓,1,   other↑,1,   p16↑,1,   P21↑,4,   P21↝,1,   p‑p38↑,1,   p‑p42↓,1,   p‑p44↓,1,   p50↓,1,   P53↓,1,   P53↑,3,   P53↝,1,   p‑P53↑,2,   p62↓,1,   p62↑,3,   p65↓,1,   PAO↑,1,   PARP↑,1,   p‑PARP↑,1,   cl‑PARP↑,3,   PFK1↓,1,   pH↑,1,   PI3K↝,1,   PIAS-3↑,1,   PKM2↓,2,   PSA↝,1,   PTEN↑,1,   PTEN↝,1,   PTP1B↓,1,   PUMA↑,1,   RAD51↑,1,   radioP↑,1,   RadioS↑,2,   Raf↓,1,   RAS↓,1,   REL↑,1,   ROS↓,3,   ROS↑,42,   ROS⇅,1,   ROS↝,1,   SDH↑,1,   selectivity↑,2,   SOCS-3↑,1,   SOCS1↑,1,   SOD1↓,1,   SOX2↓,1,   SOX9?,1,   Sp1/3/4↓,3,   Src↓,2,   SSAT↑,1,   p‑STAT1↓,1,   STAT3↓,3,   p‑STAT3↓,2,   T-Cell↑,2,   TGF-β↓,2,   TNF-α↝,1,   TP53↑,1,   Trx↓,1,   Trx1↓,2,   Trx2↓,1,   TrxR↓,4,   TrxR1↓,1,   TumAuto↓,1,   TumAuto↑,3,   TumCCA↑,7,   TumCG↓,3,   TumCMig↓,2,   TumCP↓,4,   tumCV↓,3,   TumVol↓,1,   UPR↑,1,   USF1↑,1,   VEGF↓,2,   VEGF↝,1,   Vim↓,1,   xCT↓,1,   XIAP↓,1,   ZBTB10↑,1,   α-SMA↓,1,   β-catenin/ZEB1↓,1,   β-catenin/ZEB1↝,1,   γH2AX↑,1,   p‑γH2AX↑,1,  
Total Targets: 225

Results for Effect on Normal Cells:
5LO↓,1,   Ach↑,1,   AChE↓,2,   AIF↓,1,   Akt↓,1,   Akt↑,1,   ALAT↓,2,   ALP↓,1,   antiOx↓,3,   antiOx↑,4,   AP-1↓,2,   Apoptosis↓,1,   AST↓,2,   ATP↑,1,   Aβ↓,4,   BBB↑,2,   Bcl-2↑,1,   BioAv↓,2,   BioAv↑,1,   BioAv↝,1,   cardioP↑,1,   Casp3↓,1,   Casp9↓,1,   Catalase↑,3,   ChAT↑,1,   cognitive↑,5,   COL3A1↓,1,   COX2↓,4,   COX2↑,1,   DNAdam↓,1,   Dose↝,1,   eff↑,1,   Ferritin↑,1,   GPx↑,3,   GSH↑,8,   GSK‐3β↓,1,   GSR↓,1,   GSTs↑,1,   H2O2↓,1,   Half-Life↝,1,   HATs↓,1,   HDAC↑,1,   hepatoP↑,3,   HO-1↑,4,   HO-2↓,1,   ICAM-1↓,1,   IL1↓,1,   IL12↓,1,   IL1β↓,4,   IL2↓,1,   IL2↑,1,   IL4↓,1,   IL6↓,2,   IL8↓,1,   INF-γ↓,1,   Inflam↓,9,   iNOS↓,1,   IronCh↑,2,   LDH↓,1,   LDL↓,1,   lipid-P↓,4,   MCP1↓,2,   MDA↓,5,   memory↑,3,   MMP2↓,1,   MMP3↓,1,   MMP9↓,1,   NADPH↑,1,   neuroP↑,4,   NF-kB↓,5,   NLRP3↓,1,   NO↓,3,   NO↑,1,   NRF2↑,6,   p300↓,1,   PGE2↓,2,   PI3K↑,1,   ROS?,1,   ROS↓,16,   SOD↑,5,   STAT↓,1,   STAT3↓,1,   tau↓,1,   TNF-α↓,3,   toxicity↓,1,   toxicity∅,1,   α-SMA↓,1,  
Total Targets: 87

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
56 Curcumin
6 Resveratrol
3 Radiotherapy/Radiation
3 Chemotherapy
3 Quercetin
2 Ursolic acid
1 Alpha-Lipoic-Acid
1 Boron
1 Ellagic acid
1 Berberine
1 Cisplatin
1 Melatonin
1 Silymarin (Milk Thistle) silibinin
1 5-fluorouracil
1 Myricetin
1 Vitamin C (Ascorbic Acid)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:65  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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