Ca+2 Cancer Research Results

Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
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In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
Scientific Papers found: Click to Expand⟱
3864- ACNs,    Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain
*Aβ↓,
*ROS↓,
*cognitive↑, Mulberries are a rich source of ANTs that induce antioxidant enzymes and promote cognition
*APP↓, In the cerebral cortex, blackcurrant and bilberry extract reduced APP levels in AD mouse models, but changes in the expression or phosphorylation of tau-protein were not observed
*BBB↑, ANTs cross the blood-brain barrier and protect brain tissue from Abeta toxicity
*Ca+2↓, Aronia melanocarpa. ANTs of this plant decrease intracellular calcium and ROS but increase ATP and mitochondrial potential.
*ATP↑,
*BACE↓, An-NPs also attenuate the protein expression of BACE-1 neuroinflammatory markers, such as phosphonuclear factor kB (p-NF-kB), tumor-necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS),
*p‑NF-kB↓,
*TNF-α↓,
*iNOS↓,

3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, Alpha-lipoic acid (α-LA), a natural antioxidant
*memory↑, multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects
*neuroP↑, α-LA could be considered neuroprotective
*Inflam↓, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies.
*IronCh↑, α-LA leads to a marked downregulation in iron absorption and active iron reserve inside the neuron
*NRF2↑, α-LA induces the activity of the nuclear factor erythroid-2-related factor (Nrf2), a transcription factor.
*BBB↑, capable of penetrating the BBB
*GlucoseCon↑, Fig 2, α-LA mediated regulation of glucose uptake
*Ach↑, α-LA may show its action on the activity of the ChAT enzyme, which is an essential enzyme in acetylcholine metabolism
*ROS↓,
*p‑tau↓, decreased degree of tau phosphorylation following treatment with α-LA
*Aβ↓, α-LA possibly induce the solubilization of Aß plaques in the frontal cortex
*cognitive↑, cognitive reservation of α-LA served AD model was markedly upgraded in additional review
*Hif1a↑, α-LA treatment efficaciously induces the translocation and activity of hypoxia-inducible factor-1α (HIF-1α),
*Ca+2↓, research found that α-LA therapy remarkably declines Ca2+ concentration and calpain signaling
*GLUT3↑, inducing the downstream target genes expression, such as GLUT3, GLUT4, HO-1, and VEGF.
*GLUT4↑,
*HO-1↑,
*VEGF↑,
*PDKs↓, α-LA also ameliorates survival in mutant mice of Huntington's disease [150–151], possibly due to the inhibition of the activity of pyruvate dehydrogenase kinase
*PDH↑, α-LA administration enhances PDH expression in mitochondrial hepatocytes by inhibiting the pyruvate dehydrogenase kinase (PDK),
*VCAM-1↓, α-LA inhibits the expression of cell-cell adhesion molecule-1 and VCAM-1 in spinal cords and TNF-α induced neuronal endothelial cells injury
*GSH↑, α-LA may enhance glutathione production in old-aged models
*NRF2↑, activation of the Nrf2 signaling by α-LA
*hepatoP↑, α-LA also protected the liver against oxidative stress-mediated hepatotoxicity
*ChAT↑, α-LA in mice models may prevent neuronal injury possibly due to an increase in ChAT in the hippocampus of animal models

2478- Ba,    The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway
- in-vitro, BC, MDA-MB-231
Bcl-2↓, Baicalein induced apoptosis in a time-dependent effect through the inhibition of Bcl-2 expression, increased the levels of Bax
BAX↓,
Cyt‑c↑, promoted the cytochrome c release and caspase-3 activation.
Casp3↑,
Ca+2↓, baicalein induced apoptosis via Ca2+ production, mitochondria-dependent and caspase-3 activation in MDA-MB-231 cells.

2601- Ba,    Cardioprotective effects of baicalein on heart failure via modulation of Ca2 + handling proteins in vivo and in vitro
- in-vitro, Nor, NA - in-vivo, Nor, NA
*cardioP↑, First, we demonstrated baicalein improved cardiac function and prevented LV hypertrophy.
*p‑Ca+2↓, including downregulation of phosphorylation of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) and expression of Na(+)/Ca(2 +)-exchangers (NCX1), upregulation of sarcoplasmic reticulum Ca(2 +) ATPase 2 (SERCA2) and ryanodine receptor 2 (RYR2)

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

2670- BBR,    Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
- Review, Var, NA
*Inflam↓, According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity
*antiOx↑,
*Ca+2↓, Impaired cerebral arterial vasodilation can be alleviated by berberine in a diabetic rat model via down-regulation of the intracellular Ca2+ processing of VSMCs
*BioAv↓, poor oral absorption and low bioavailability
*BioAv↑, Conversion of biological small molecules into salt compounds may be a method to improve its bioavailability in vivo.
*BioAv↑, Long-chain alkylation (C5-C9) may enhance hydrophobicity, which has been shown to improve bioavailability; for example, 9-O-benzylation further enhances lipophilicity and imparts neuroprotective effect
*angioG↑, figure 2
*MAPK↓,
*AMPK↓, 100 mg/kg berberine daily for 14 days attenuated ischemia–reperfusion injury via hemodynamic improvements and inhibition of AMPK activity in both non-ischemic and ischemic areas of rat heart tissue
*NF-kB↓,
VEGF↓,
PI3K↓,
Akt↓,
MMP2↓,
Bcl-2↓,
ERK↓,

2684- BBR,    Berberine is a Novel Mitochondrial Calcium Uniporter Inhibitor that Disrupts MCU‐EMRE Assembly
- in-vivo, Nor, NA
*MCU↓, These findings establish Berberine as a potent MCU inhibitor, offering a safe therapeutic strategy for diseases associated with dysregulated mitochondrial calcium homeostasis.
*mt-Ca+2↓, Berberine pretreatment reduces mitochondrial Ca2+ overload and mitigates ischemia/reperfusion‐induced myocardial injury in mice.
*cardioP↑, Berberine significantly reduces mitochondrial Ca2+ overload, providing cardioprotection against I/R‐induced myocardial injury in mice.

3509- Bor,    Boron and Prostate Cancer a Model for Understanding Boron Biology
- NA, Pca, NA
Ca+2↓, boric acid inhibits calcium (Ca²+) release from the endoplasmic reticulum. NAD+ stimulated release of Ca2+ was greatly diminished in the presence of boric acid

3511- Bor,    Boron
- Review, NA, NA
*memory↑, In boron-deprived humans, boron supplementation improved mental alertness, attention, short-term memory, and motor speed and dexterity.
*motorD↑,
*neuroP↑,
Ca+2↓, human prostate cells, boric acid acts as a reversible noncompetitive inhibitor of cADPR leading to decreased endoplasmic reticulum Ca2+
ATF4↑, The decreased Ca2+ results in the E74 like ETS transcription factor 2α activating transcription factor 4 (ATF4) and nuclear factor erythroid 2 like 2 (Nrf2),
NRF2↑,
*Inflam↓, a dietary boron intake >0.4 mg/d may be useful for bone and brain health and in modulating inflammatory and oxidative stress
*ROS↓,

3512- Bor,    Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake
- in-vitro, Pca, DU145
TumCP↓, Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α).
eIF2α↑, Phosphorylation of eIF2α occurs following BA treatment of DU-145 and LNCaP prostate cells
ATF4↑, post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively
ATF6↑,
GADD34↑, The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp),
CHOP↓, but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene.
GRP78/BiP↑, The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM.
GRP94↑,
Risk↓, Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration
*BMD↑,
Ca+2↓, LNCaP and DU-145: BA binds to cADPR and inhibits cADPR-activated Ca2+ release from the endoplasmic reticulum (ER) in a dose-dependent manner [15, 16] and lowers ER luminal Ca2+ concentrations
*Half-Life↝, lood levels of BA are dynamic, rising rapidly after a meal with an elimination half-life from 4 to 27.8 h depending on dose
IRE1∅, BA does not activate IRE1
chemoP↑, Dietary boron has been connected to three seemingly unconnected observations, increased bone mass and strength [10, 74, 75], chemoprevention

746- Bor,    Organoboronic acids/esters as effective drug and prodrug candidates in cancer treatments: challenge and hope
- Review, NA, NA
eff↑, newly developed boron-containing compounds have already demonstrated highly promising activities
*toxicity↓, Boronic acid/ester has been successfully incorporated into cancer treatments and therapy mainly due to its remarkable oxophilicity and low toxicity levels in the body
ROS↑, can trigger tumour microenvironmental abnormalities such as high levels of reactive oxygen species (ROS) and overexpressed enzymes
LAT↓, boron accumulation were observed to counterpart LAT-1 expression in a bone metastasis model of breast cancer
AntiCan↑, high concentration of boron in males reduces the probability of prostate cancer by 54% compared to males with low boron concentrations
AR↓, bortezomib
PSMB5↓, bortezomib
IGF-1↓, insulin-like growth factor 1 (IGF-1) in tumours was markedly reduced by boric acid.
PSA↓, exposure to both low-and high-dose boron supplementation, prostate-specific antigen (PSA) levels dropped by an average of 87%, while tumour size declined by an average of 31.5%
TumVol↓,
eff↑, phenylboronic acid is a more potent inhibitor than boric acid in targeting metastatic and proliferative properties of prostate cancer cells
Rho↓, RhoA, Rac1
Cdc42↓,
Ca+2↓, ER Ca+2 depletion occurred after the treatment of DU-145 prostate cancer cells with the physiological concentrations of boric acid
eff↑, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) against SCLC cell line using DMS-114 cells

760- Bor,    Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer’s Disease
- in-vivo, AD, NA
*memory↑, BA reduced damage to learning and memory functions and significantly lowered oxidative stress markers in the AD model.
*ROS↓, been reported that BA also reduces oxidative stress by increasing glutathione reserves,
*GSH↑,
*Aβ↓, and strongly inhibits Aβ aggregation via hydroxyl group
*Inflam↓, BA can act as a protective agent in apoptotic processes by regulating oxidative and inflammatory processes as well as mitochondrial membrane potential
*MMP↑,
*lipid-P↓, BA added to the diet prevented lipid peroxidation by supporting and strengthening the antioxidant defense system.
*Ca+2↓, Boron is thought to prevent apoptosis and strengthen antioxidant defense by reducing intracellular oxygen radicals and calcium levels.
*cognitive↑, Our hypothesis is that boric acid can improve cognitive function and histopathological outcomes by reducing oxidative stress in rats with STZ-induced Alzheimer’s Disease
*TOS↓, After BA administration, it increased TAS by increasing the antioxidant effect, and as a result, TOS and OSI decreased.

710- Bor,    Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells
- in-vitro, Pca, DU145
NAD↓, inhibits NAD+ and NADP+
TumCP↓, Cell proliferation was inhibited by 30% at 100 microM, 60% at 250 microM, and 97% at 1,000 microM BA
CD38↑,
Ca+2↓, hypothesize that toxicity of BA stems from the ability of high concentrations to impair Ca2+ signaling.

711- Bor,    Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells
- in-vitro, Pca, DU145
Ca+2↓, exposure of DU-145 cells to 50 µM BA for 1 hr decreased stored [Ca2+] by 32%.

6002- CGA,    Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials
- Review, Var, NA - Review, Diabetic, NA - Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms

6082- CHOC,    Potential for preventive effects of cocoa and cocoa polyphenols in cancer
- Review, Var, NA
*ROS↓, Cocoa flavonoids have been demonstrated to influence several important biological functions in vitro and in vivo by their free radical scavenging ability
Apoptosis↑, or through the regulation of signal transduction pathways to stimulate apoptosis and to inhibit inflammation, cellular proliferation, apoptosis, angiogenesis and metastasis.
Inflam↓,
TumCP↓,
angioG↓,
TumMeta↓,
*Ca+2↓, oxidative stress in lead-exposed cells through the downregulation of ROS generation, decrease of intracellular calcium and prevented the alteration of the mitochondrial membrane potential
*MMP∅,
CYP1A1↑, A polyphenolic cocoa extract increased CYP1A1 mRNA and protein levels and enzymatic activity in MCF-7 and SKBR3 breast cancer cells
PGE2↓, Cocoa phenolic extract inhibited the inflammatory mediator prostaglandin E2 in human intestinal Caco-2 cells
TumCCA↑, Cocoa-derived pentameric procyanidin (pentamer) caused G0/G1 cell cycle arrest in human breast cancer MDA MB-231,
chemoPv↑, This study demonstrated that a co- coa-rich diet could prevent the early stage of chemically induced colorectal cancer in rats

1585- Citrate,    Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer
- in-vitro, Ovarian, SKOV3 - in-vitro, Ovarian, A2780S - in-vitro, Nor, HEK293
Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1584- Citrate,    Anticancer effects of high-dose extracellular citrate treatment in pancreatic cancer cells under different glucose concentrations
- in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1
tumCV↓, Extracellular sodium citrate significantly reduced cell viability partially due to reduction in intracellular Ca2+ levels
i-Ca+2↓, Intracellular Ca2+ levels were significantly reduced by 28.5 %
TumCMig↓,
CD133↓, decrease in the levels of the stem cell marker prominin I (CD133) following sodium citrate treatment.
pH↑, pH slightly increased upon administration of sodium citrate
eff↑, findings suggest that exogenous sodium citrate treatment, particularly in combination with gemcitabine, may represent a novel therapeutic strategy for treating PDAC.
Ki-67↓, sodium citrate treatment decreased the percentage of Ki67-positive cells
eff↑, sodium citrate treatment may have a more pronounced anticancer effect on glycolytic pancreatic cancer cells with high expression of SLC13A5.

1580- Citrate,    Citrate activates autophagic death of prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway
- in-vitro, Pca, PC3 - in-vivo, PC, NA - in-vitro, Pca, LNCaP - in-vitro, Pca, WPMY-1
Apoptosis↑,
Ca+2↓, Ca2+-chelating property of citrate
Akt↓, downregulation CaMKII/AKT/mTOR pathway
mTOR↓,
selectivity↑, citrate (0-3 mM) did not affect the cell growth of normal prostate epithelial cells (WPMY-1).
TumCP↓, also verified that citrate significantly inhibited the proliferation of PCa cells (PC3 and LNCaP).
cl‑Casp3↑,
cl‑PARP↑, increased the levels of Cleaved caspase3 and Cleaved PARP in prostate cancer cells
LC3‑Ⅱ/LC3‑Ⅰ↑, ratio of LC3-II/I was markedly increased and the expression of p62 was significantly decreased after the treatment of citrate in PCa cells (PC3 and LNCaP).
p62↓,
ATG5↑, citrate also promoted the protein expression of Atg5, Atg7 and Beclin-1 in PCa cells (PC3 and LNCaP).
ATG7↑,
Beclin-1↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII ↓, citrate suppresses the activation of the CaMKI

1576- Citrate,    Targeting citrate as a novel therapeutic strategy in cancer treatment
- Review, Var, NA
TCA↓, Citrate serves as a key metabolite in the tricarboxylic acid cycle (TCA cycle, also referred to as the Krebs cycle)
T-Cell↝, modulation of T cell differentiation
Glycolysis↓, Citrate directly suppresses both cell glycolysis and TCA.
PKM2↓, citrate also inhibits glycolysis via its indirect inhibition of PK
PFK2?, In addition, citrate can inhibit PFK2,
SDH↓, citrate can inhibit enzymes, such as succinate dehydrogenase (SDH) and pyruvate dehydrogenase (PDH), in the TCA cycle
PDH↓,
β-oxidation↓, Citrate also inhibits β-oxidation as it promotes the formation of malonyl-CoA, which decreases the mitochondrial transport of fatty acids by inhibiting carnitine palmitoyl transferase I (CPT I)
CPT1A↓,
FASN↑, citrate has a positive role in promoting fatty acid synthesis
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Hif1a↓, Notably, in AML cell line U937, citrate induces apoptosis in a dose- and time-dependent manner by regulating the expression of HIF-1α and its downstream target GLUT-1
GLUT1↓,
angioG↓, citrate can also inhibit angiogenesis
Ca+2↓, chelate calcium ions in tumor cells
ROS↓, The other potential mechanism involved in citrate-mediated promotion of cancer growth and proliferation may be through its ability to decrease the levels of reactive oxygen species (ROS) in tumor cells
eff↓, dual effects of citrate in tumors may depend on the concentrations of citrate treatment, and different concentrations may bring out completely opposite effects even in the same tumor.
Dose↓, citrate concentration (<5 mM) appears to boost tumor growth and expansion in lung cancer A549 cells. 10mM and higher inhibited cell growth.
eff↑, citrate combined with ultraviolet (UV) radiation caused activation of caspase-3 and -9 in tumor cells (
Mcl-1↓, citrate has also been found to downregulate Mcl-1
HK2↓, Citrate also inhibits the enzymes PFK1 and hexokinase II (HK II) in glycolysis in tumor cells
IGF-1R↓,
PTEN↑, citrate may exert its effect via activating PTEN pathway
citrate↓, In addition to prostate cancer, citrate levels are significantly decreased in blood of patients with lung, bladder, pancreas and esophagus cancers
Dose∅, daily oral administration of citrate for 7 weeks at dose of 4 g/kg/day reduces tumor growth of several xenograft tumors and increases significantly the numbers of tumor-infiltrating T cells with no significant side effects in mouse models
eff↑, combining citrate with other compounds such as celecoxib, cisplatin, and 3-bromo-pyruvate, and have generated promising results
eff↑, combination of low effective doses of 3-bromo-pyruvate (3BP) (15uM), an inhibitor of glycolysis, and citrate (3 mM) significantly depleted the proliferation capability and migratory power of the C6 glioma
eff↑, Zinc treatment could lead to citrate accumulation in malignant prostate cells, which could have therapeutic potential in clinical therapy of prostate cancer.
eff↑, synergistic efficacy mediated by citrate combined with current checkpoint blockade therapies with anti-CTLA4 and/or anti-PD1/PDL1 will develop alternative novel strategies for future immunotherapy.

2315- Citrate,    Why and how citrate may sensitize malignant tumors to immunotherapy
- Review, Var, NA
Bcl-2↓, SCT can induce silent apoptosis by reducing expression of key pro-apoptotic proteins (Bcl-2, surviving, MCL1), and promoting the activation of caspases-3 and −9 and −8, as showed in multiple cancer cell lines
Mcl-1↓,
survivin↓,
Casp3↑,
Casp9↑,
Ferroptosis↑, SCT can also trigger ferroptosis, an iron-dependent form of lytic cell death inducing lipid peroxidation (LPO)
lipid-P↑,
Ca+2↓, citrate lowers mitochondrial Ca2+ concentration by chelation
Akt↓, by chelating cytosolic Ca2+, citrate inhibits the Ca2+/CAMKK2/AKT/mTOR signaling pathway, thereby suppressing HIF1-α dependent glycolysis
mTOR↓,
Hif1a↓,
MCU↓, reduces the activity of the mitochondrial calcium uniporter (MCU), resulting in decreasing ATP production, increasing ROS production
ATP↓,
ROS↑,
eff↑, Of note, ferroptosis can enhance the effectiveness of immunotherapy, as showed in glioma models

3631- Cro,    Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease
- in-vitro, AD, HT22 - in-vivo, AD, NA
*ROS↓, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells.
*Ca+2↓, crocin strongly inhibited the overload of Ca2+ compared with the l-Glu-damaged HT22 cells,
*BAX↓, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase-3
*BAD↓,
*Casp3↓,
*cognitive↑, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test,
*memory↑,
*Aβ↓, Crocin improved cognitive abilities of AD mice, and reduced Aβ deposition in their brains
*GPx↑, crocin was able to reduce the Aβ1-42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase,
*SOD↑,
*ChAT↑,
*Ach↑,
*AChE↓, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice.
*ROS↓,
*p‑Akt↑, crocin upregulated the phosphorylation levels of Akt and mTOR in 24-h l-Glu-exposed cells.
*p‑mTOR↑,
*neuroP↑, crocin-mediated neuroprotection of l-Glu-damaged HT22 cells.

3831- CUR,    Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, Several studies have shown that C. longa is a potential neuroprotective drug
*ROS↓, Curcumin inhibited Aβ-induced DNA damage by reducing of ROS generation through p38 MAPK and AKT pathways
*Ca+2↓, attenuate apoptosis by regulating intracellular Ca2+ release, ROS, and mitochondrial membrane potential depolarization level in SH-SY5Y cells
*MMP↑,

1877- DCA,    Non-Hodgkin′s Lymphoma Reversal with Dichloroacetate
- Case Report, lymphoma, NA
Remission↑, Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later.
p‑PDKs↓, DCA has been shown to block this phosphorylation by PDK at the mitochondrial membrane level and decrease glycolysis in favor of glucose oxidation
Glycolysis↓,
i-Ca+2↓, This return to a normal metabolism of glucose allows for major changes including a decrease in Ca++ intracellularly, and stabilization of the mitochondria allowing a reactivation of caspases in cancer cells leading to apoptosis
toxicity↓, A reversible, minimal nerve damage can be considerably reduced by a daily thiamine intake of several hundred milligrams for humans. thiamine amount varies from 50 mg/day to 100 mg/day depending on whether it is administered orally or injected
Dose∅, A Non-Hodgkin′s lymphoma patient taking 10 mg/kg [750 mg] of dichloroacetate daily of his own accord, had a complete remission of his Non-Hodgkin′s lymphoma cancer after four months

5196- DCA,    Dichloroacetate induces apoptosis in endometrial cancer cells
- in-vitro, Var, NA
selectivity↑, Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells.
MMP↓, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism.
survivin↓,
Ca+2↓, DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway.
P53↑, DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism.
PDK1↓, DCA binds to PDK and attenuates inhibition of PDH activity.
PDH↑,
Glycolysis↓, The increased PDH activity shifts metabolism from glycolysis to glucose oxidation and decreases mitochondrial membrane potential (MMP) hyperpolarization
OXPHOS↑,
ROS↑, translocation of reactive oxygen species (ROS) and cytochrome c from the mitochondria to the cytoplasm, subsequently inducing apoptosis through the activation of caspases
Cyt‑c↑,
Apoptosis↑,
Casp↑,
tumCV↓, DCA Reduces Endometrial Cancer Cell Viability in a Dose-Dependent Manner
PUMA↑, DCA Increases PUMA Expression

3206- EGCG,    Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration
- Review, AMD, NA
*Ca+2↓, EGCG restores [Ca2+]i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis.
*ROS↓,
*Apoptosis↓,
*GRP78/BiP↓, EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells
*CHOP↓,
*PERK↓,
*IRE1↓,
*p‑PARP↓,
*Casp3↓,
*Casp12↓,
*ER Stress↓,
*UPR↓, EGCG mitigates ER stress; maintain calcium homeostasis and inhibition of UPR to control the progression of AMD.

3594- EGCG,    Epigallocatechin-3-gallate inhibits secretion of TNF-alpha, IL-6 and IL-8 through the attenuation of ERK and NF-kappaB in HMC-1 cells
- in-vitro, AD, HMC1
*TNF-α↓, EGCG (100 microM) inhibited PMA+A23187-induced TNF-alpha, IL-6 and IL-8 expression and production.
*IL6↓,
*IL8↓,
*Ca+2↓, EGCG inhibited the intracellular Ca(2+) level.

1974- EGCG,    Protective Effect of Epigallocatechin-3-Gallate in Hydrogen Peroxide-Induced Oxidative Damage in Chicken Lymphocytes
- in-vitro, Nor, NA
*ROS↓, suppressed the increase in intracellular reactive oxygen species (ROS), nitric oxide (NO),
*NO↓,
*MMP↑, preincubation of the cells with EGCG increased mitochondrial membrane potential (MMP) and reduced calcium ion ([Ca2+]i) load.
*i-Ca+2↓, EGCC Increased Mitochondrial Membrane Potential and Decreased [Ca2+]i
*HO-1↑, expression of SOD, Heme oxygenase-1 (HO-1), Catalase (CAT), GSH-PX, nuclear factor erythroid 2-related factor 2 (Nrf2), and thioredoxin-1 (Trx-1).
*Catalase↑,
*NRF2↑,
*Trx1↑,
*antiOx↑, EGCC Increased Antioxidant Capacity
*SOD↑, EGCC Decreased ROS and Increased SOD Generation
*Apoptosis↓,

2468- EGCG,    Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists
- in-vitro, Nor, NA
*AntiAg↑, EGCG inhibits platelet activation, by hindering the thrombin proteolytic activity, and by reducing the agonist-induced [Ca(2+)](c) increase through inhibition of Syk and Lyn activities.
*Ca+2↓,

4071- FA,    Folate and Alzheimer: when time matters
- Review, AD, NA
*cognitive↑, olate deficiency is a risk factor for neural tube defects and late in life for cognitive decline and Alzheimer's dementia (AD).
*ROS↓, Deficiency induces several Alzheimer pathomechanisms like oxidative stress, Ca(++) influx, accumulation of hyperphosphorylated tau and β-amyloid
*Ca+2↓,
*p‑tau↓,
*Aβ↓,

3778- FA,    Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review
- Review, AD, NA
*neuroP↑, it seems to ameliorate AD pathology by preventing neurodegeneration in several brain regions;
*Aβ↓, it has been shown to inhibit Aβ oligomer aggregations and to exert antioxidant, anti-inflammatory, and anti-apoptotic effects
*antiOx↑,
*Inflam↓,
*ROS↓, ability of ferulic acid to prevent oxidative stress
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B),
*NLRP3↓, it also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), has been observe
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK?, inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK),
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen in a mouse model of hepatotoxicity by inhibiting the expression of toll like receptor 4 (TLR4),
*TLR4↓,
*PPARγ↑, ferulic acid upregulated PPARγ and Nrf2 expression in renal cells,
*NRF2↑,
*Fenton↓, Ferulic acid may also inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu),
*IronCh↑,
*MDA↓, a lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker
*HO-1↑, Ferulic acid has been found able to upregulate HO-1, thus increasing the production of bilirubin, which acts as an efficient ROS scavenger,
*Bil↑,
*GCLC↑, (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic acid
*GCLM↑,
*NQO1↑,
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*SOD↑, Indeed, it prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*Ca+2↓,
*lipid-P↓,
*PGE2↓,

3714- FA,    Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review
- Review, AD, NA
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells

3771- H2,    Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?
- Review, AD, NA - Review, Stroke, NA
*cognitive↑, hydrogen improves cognitive and neurological deficits and prevents or delays the onset of neurodegenerative changes in the brain.
AntiCan↑, Chinese National Health and Medical Commission in 2020 recommended the use of inhaled hydrogen in addition to oxygen therapy for anti-cancer, anti-inflammatory and anti-oxidant treatments
*Inflam↓,
*antiOx↑,
*ROS↓, Hydrogen has been suggested as a new complementary therapy against stroke, which, e.g., reduces oxidative stress,
*neuroP↑, Molecular Hydrogen Neuroprotection in Post-Ischemic Brain Injury
*SOD↑, molecular hydrogen significantly increases SOD and GSH-Px activity, reduces malondialdehyde levels and infarct volume, relieves cerebral edema, improves neurological outcomes and alleviates cognitive deficits
*GPx↑,
*MDA↑,
*BBB↑, Molecular hydrogen has been shown to protect the permeability of the blood-brain barrier after focal and global cerebral ischemia
*OS↑, It was documented that hydrogen therapy significantly improved the 7-day survival rate of mice after global brain ischemia, from 8.3 to 50%
*Ca+2↓, In addition, hydrogen lowered the increased levels of intracellular Ca2+ caused by glutamate toxicity
*APP↓, Taken together, these results indicate that treatment with hydrogen-rich water prevents proteolysis of the amyloid protein precursor towards amyloid
*p‑tau↓, hydrogen-rich water significantly inhibited the phosphorylation of the tau protein

3764- H2,    Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model
- in-vivo, AD, NA
*memory↑, However, after H2 treatment, memory deficits were ameliorated.
*Aβ↓, H2 treatment also decreased AD-related biomarkers, such as Apo-E, Aβ-40, p-tau, and Bax and OS markers such as ROS, NO, Ca2+, and MDA in both serum and brain.
*p‑tau↓,
*BAX↓,
*ROS↓,
*NO↓,
*Ca+2↓,
*MDA↓,
*Catalase↓, In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H2 gas treatment in serum and brain
*GPx↓,
*TNF-α↓, (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H2 treatment in both serum and brain lysates
*Bcl-2↑, In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H2 treatment.
*VEGF↑,
*Inflam↓, 2% H2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers.
*cognitive↑,

4238- HNK,    Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint
- Review, AD, NA - NA, Park, NA
*BDNF↑, honokiol treatment led to an improvement in plasma BDNF levels.
*hepatoP↑, prevented liver damage by reducing transaminase levels (ALT and AST), liver OS, and TNF-α activity in mice challenged with LPS.
*ALAT↓,
*AST↓,
*TNF-α↓,
*SIRT3↑, 0.5, 1, 2, 5, 10 and 20 μM Enhanced SIRT3 expression, reduced Aβ levels
*Aβ↓,
*Apoptosis↓, Honokiol exhibited a dose-dependent reduction in hippocampal neural apoptosis, ROS generation, and decline in the membrane potential of mitochondria caused by AβO
*ROS↓,
*MMP↑,
*Ca+2↓, Dose-dependent reduction of ROS, suppression of intracellular Ca elevation, and inhibition of caspase-3 activity
*Casp3↓,
*Ach↑, Increased extracellular acetylcholine release to 165.5 ± 5.78% of the basal level
*PPARγ↑, Increased the expression of PPARγ and PGC1α
*PGC-1α↑,
*motorD↑, Improvement of motor dysfunction due to reversal of nigrostriatal dopaminergic neuronal loss
*TNF-α↓, Attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro
*IL1β↓,

2869- HNK,    Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's
- Review, AD, NA - Review, Park, NA
*neuroP↑, neuroprotective, anti-oxidant, anti-apoptotic, neuromodulating, anti-inflammatory, and many more qualities, honokiol,
*Inflam↓,
*motorD↑, degradation of dopaminergic neurons in Parkinson's disease and improving motor function.
*Aβ↓, Alzheimer's disease, honokiol showed promise in lowering the production of amyloid-beta (Aβ) plaques, phosphorylating tau, and enhancing cognitive performance
*p‑tau↓,
*cognitive↑,
*memory↑, prevented Acetylcholinesterase activity from elevation as well as improved acetylcholine levels, and improved learning, and memory deficits via increased ERK1/2 and Akt phosphorylation
*ERK↑,
*p‑Akt↑,
*PPARγ↑, honokiol has been reported to elevate PPARγ levels in APPswe/PS1dE9 mice as PPARγ is related to ani-inflammatory
*PGC-1α↑, honokiol boosted the expression of PGC1α and PPARγ
*MMP↑, as well as reduced elevated mitochondrial membrane potential and mitochondrial ROS
*mt-ROS↓,
*SIRT3↑, Honokiol has been found as a dual SIRT-3 activator and PPAR-γ agonist that reduced oxidative stress markers within cells and changed the AMPK pathway
*IL1β↓, honokiol prevented restraint stress-induced cognitive dysfunction by reducing the hippocampus's production of IL-1β, TNF-α, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)
*TNF-α↓,
*GRP78/BiP↓,
*CHOP↓,
*NF-kB↓, Additionally, the neuroprotective benefits of honokiol in mice with Aβ-induced learning and memory impairment have been attributed to the inactivation of NF-κB
*GSK‐3β↓, Treatment of honokiol in PC12 cells resulted in reduced GSK-3β and induced β-catenin which effectively showed the neuroprotective and anti-oxidant effect in AD therapy
*β-catenin/ZEB1↑,
*Ca+2↓, , anti-apoptotic effect via reduced caspase 3 levels, and protected membrane injury by reduced calcium level has been investigated in PC12 cells of AD models
*AChE↓, protective effects by serving as an antioxidant, reduced AchE levels, repaired neurofibrillary tangles, reduced NF-kB which downregulates Aβ plaque
*SOD↑, fig1
*Catalase↑,
*GPx↑,

3268- Lyco,    Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders
- Review, AD, NA
*BioAv↓, Lycopene bioavailability can be decreased by ageing, and some of the pathological states, such as cardiovascular diseases (CVDs)
*AntiCan↑, For instance, it has been shown that a higher dietary intake and circulating concentration of lycopene have protective effects against prostate cancer (PCa), in a dose-dependent way
*ROCK1↓, It remarkably lessened the expression of ROCK1, Ki-67, ICAM-1 and ROCK2,
*Ki-67↓,
*ICAM-1↓,
*cardioP↑, Lycopene is a cardioprotective nutraceutical.
*antiOx↑, Lycopene is a well-known antioxidant.
*NQO1↑, Furthermore, lycopene supplementation improves mRNA expressions of the NQO-1 and HO-1 as antioxidant enzymes.
*HO-1↑,
*TNF-α↓, downregulate inflammatory cytokines (i.e., TNF-α, and IL-1β) in the hippocampus of the mice.
*IL22↓,
*NRF2↑, Lycopene decreased neuronal oxidative damage by activating Nrf2, as well as by inactivating NF-κB translocation in H2O2-related SH-SY5Y cell model
*NF-kB↓,
*MDA↓, significantly reduced the malondialdehyde (MDA)
*Catalase↑, Furthermore, it improved the catalase (CAT), superoxide dismutase (SOD), and GSH levels, and antioxidant capacity [109].
*SOD↑,
*GSH↑,
*cognitive↑, Lycopene administration considerably improved cognitive defects, noticeably reduced MDA levels and elevated GSH-Px activity, and remarkably reduced tau
*tau↓,
*hepatoP↑, Lycopene was also found to be effective against hepatotoxicity by acting as an antioxidant, regulating total glutathione (tGSH) and CAT concentrations
*MMP2↑, It also elevated MMP-2 down-regulation
*AST↓, lowering the liver enzymes levels, like aspartate transaminase (AST), alanine transaminase (ALT), LDL, free fatty acid, and MDA.
*ALAT↓,
*P450↑, Moreover, tomato powder has been shown to have a protective agent against alcohol-induced hepatic injury by inducing cytochrome p450 2E1
*DNAdam↓, lycopene decreased DNA damage
*ROS↓, It has been revealed that they inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity in rats’ liver
*neuroP↑, lycopene consumption relieved cognitive defects, age-related memory loss, neuronal damage, and synaptic dysfunction of the brain.
*memory↑,
*Ca+2↓, Lycopene suppressed the 4-AP-invoked release of glutamate and elevated intra-synaptosomal Ca2+ level.
*Dose↝, an in vivo study revealed that lycopene (6.5 mg/day) was effective against cancer in men [147]. However, lycopene dose should be increased up to 10 mg/day, in the case of advanced PCa.
*Dose↑, lycopene supplementation (15 mg/day, for 12 weeks) in an old aged population improved immune function through increasing natural killer cell activity by 28%
*Dose↝, Finally, according to different epidemiological studies, daily lycopene intake can be suggested to be 2 to 20 mg per day
*toxicity∅, A toxicological study on rats showed the no-observed-adverse-effect level at the highest examined dose (i.e., 1.0% in the diet)
PGE2↓, Lycopene doses of 0, 10, 20, and 30 µM were used to treat human colorectal cancer cell. Prostaglandin E2 (PGE2), and NO levels declined after lycopene administration,
CDK2↓, Treatment with lycopene reduced cell hyperproliferation induced by UVB and ultimately promoted apoptosis and reduced CDK2 and CDK4 complex in SKH-1 hairless mice
CDK4↓,
STAT3↓, lycopene reduced the STAT3 expression in ovarian tissues
NOX↓, (SK-Hep-1) cells and indicated a substantial reduction in NOX activity. Moreover, it inhibits the protein expression of NOX4, NOX4 mRNA and ROS intracellular amounts
NOX4↓,
ROS↓,
*SREBP1↓, Lycopene decreases the fatty acid synthase (FAS), sterol regulatory element-binding protein 1c (SREBP-1c), and Acetyl-CoA carboxylase (ACC1) expression in HFD mice.
*FASN↓,
*ACC↓,

2236- MF,    Changes in Ca2+ release in human red blood cells under pulsed magnetic field
- in-vitro, Nor, NA
*Ca+2↓, Pulsed magnetic field (PMF) decreases Ca2+ level of inner red blood cell (RBC).
*eff↓, PMF gives RBCs positive effect consistently in Ca2+ level and plays a role in preventing RBC hemolysis from oxidative stress and improving RBCD.
*ROS↓, PMF plays a role in preventing oxidative stress or in restoring oxidative stress on RBCs.

2237- MF,    The Effect of Pulsed Electromagnetic Field Stimulation of Live Cells on Intracellular Ca2+ Dynamics Changes Notably Involving Ion Channels
- in-vitro, AML, KG-1 - in-vitro, Nor, HUVECs
Ca+2↑, In both the KG-1 and HUVECs, PEMF stimulation resulted in enhanced Ca2+ influx
selectivity↑, response of [Ca2+]i due to PEMF stimulation appeared in the opposite direction in HUVECs.
*Inflam↓, PEMF also effected a decrease in the inflammatory cytokines TNF-alpha and NFkB in macrophage-like cells [9]. Although these studies suggest that PEMF is effective in wound healing and at attenuating inflammation
*TNF-α↓,
*NF-kB↓,
*Ca+2↓, ATP-sensitive Ca2+ influx and ER Ca2+ release of HUVECs were decreased by PEMP stimulation.

2261- MF,    Tumor-specific inhibition with magnetic field
- in-vitro, Nor, GP-293 - in-vitro, Liver, HepG2 - in-vitro, Lung, A549
ROS↑, It enhances cell oxidative stress response and regulates apoptosis signaling pathway, changing intracellular Ca2+ concentration to induce apoptosis
Ca+2↓,
Apoptosis↑,
*selectivity↑, No signicant difference was found between the exposed 293T cell count versus the control group without magnetic exposure on the third day of exposure.
TumCG↓, Hepg2, A549 cell counts were signicantly lower than the unexposed control groups (the highest inhibition rate of Hepg2 was about 18%, and the highest inhibition rate of A549 was about 30%).
*i-Ca+2↓, Normal cells 293T showed a significant decrease in intracellular free calcium ion,
i-Ca+2↑, solid tumor cells showed no signicant change, while suspended tumor showed a slight increase in calcium ion

507- MF,    Effects of extremely low frequency electromagnetic fields on the tumor cell inhibition and the possible mechanism
- in-vitro, Liver, HepG2 - in-vitro, Lung, A549 - in-vitro, Nor, GP-293
MMP↓,
TumCG↓,
ROS↑, key to tumor growth inhibition
*Ca+2↓, Normal 293 T cells showed a significant decrease in the intracellular free calcium ion concentration.
Ca+2↑, The solid tumor cells showed no significant change, while the suspended tumor cells showed a slight increase in the calcium ion concentration
selectivity↑,
i-pH↑, In addition, the intracellular pH of A549 cells increased under the magnetic field.

194- MF,    Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke
- Review, Stroke, NA
*BAD↓,
*BAX↓,
*Casp3↓,
*Bcl-xL↑,
*p‑Akt↑,
*MMP9↓, EMF significantly decreased levels of IL-1β and MMP9 in the peri-infarct area at 24 h and 3rd day of the experiment
*p‑ERK↑, ERK1/2
*HIF-1↓,
*ROS↓, n a similar experiment, ELF-MF (50 Hz/1 mT) increased cell viability and decreased intracellular ROS/RNS in mesenchymal stem cells submitted to OGD conditions and 3 h ELF-MF exposure
*VEGF↑,
*Ca+2↓,
*SOD↑,
*IL2↑,
*p38↑,
*HSP70/HSPA5↑,
*Apoptosis↓, PEMF decreased apoptosis
*ROS↓, Nevertheless, in the presence of ischemia, EMF decreased NO and ROS concentrations.
*NO↓,

199- MFrot,  MF,    Modulation of Cellular Response to Different Parameters of the Rotating Magnetic Field (RMF)—An In Vitro Wound Healing Study
- in-vivo, Wounds, L929 - NA, NA, HaCaT
*ROS↑,
*Ca+2↓,
*other↝, (i) WMF can evoke new tissue production/regeneration (stem cell proliferation and subsequent differentiation) due to manipulation of ROS levels and also downstream heat shock protein 70 (Hsp70) expression
*other↝, (ii) The magnetic field causes changes in membrane potential and temporary membrane permeabilization that affects sodium content and potassium-efflux or the transmembrane voltage
*other↝, (iii) The calcium gradient between the extracellular and intracellular fluid is a transduction second messenger [28], and its gradient could potentially be affected by EMFs and MFs.
*other↝, (iv) MF may induce changes in enzymatic activities (e.g., enzymes involved in mitochondrial metabolism).
*other↝, (v) MF may cause cytoskeletal organization (due to reorganization of the electrostatically negative charged actin filaments), and those changes may affect the cellular shape, endoplasmic reticulum, mitotic apparatus
*other?, vi) Finally, the RMF creates the mixing process at the micro-level and may affect the energy level; some of the selected molecules strongly influence the transfer processes between the living cells and the culture medium

3839- Moringa,    Nutritional Value of Moringa oleifera Lam. Leaf Powder Extracts and Their Neuroprotective Effects via Antioxidative and Mitochondrial Regulation
*eff↑, moringa methanol extracts had more phenolic content and higher antioxidant activity than acetone extracts.
*ROS↓, pretreatments with methanol extracts showed a protective effect against H2O2-induced oxidative damage through increasing cell viability and reducing free radicals.
*lipid-P↓, the extract decreased lipid peroxidation and enhanced glutathione levels and antioxidant enzyme activity.
*GSH↑,
*antiOx↑,
*Ca+2↓, Finally, moringa also prevented mitochondrial dysfunction by regulating calcium levels and increasing mitochondrial membrane potential.
*MMP↑,
*neuroP↑, Moringa oleifera as a neuroprotective agent could be beneficial to protect against oxidative stress and provide necessary nutrients for a healthy diet.
*BBB↑, Polyphenolic compounds can pass across blood-brain barrier
*Catalase↑, 53% for CAT, 51% for SOD and 65% for GPx compared to no extract cells (100%). However, pretreatments with moringa extracts reversed this impairment in the defensive system
*SOD↑,
GPx↑,

3252- PBG,    Propolis Extract and Its Bioactive Compounds—From Traditional to Modern Extraction Technologies
- Review, NA, NA
*Inflam↓, extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway.
*TNF-α↓,
*NF-kB↓,
*MAPK↓,
*ERK↓,
*antiOx↑, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway,
*NRF2↑,
*cardioP↑, pinocembrin was shown to be cardioprotective by enhancing glycolysis in the myocardium, which is an essential mechanism of action against ischemic injury of the heart
*Glycolysis↑,
*Ca+2↓, Reducing the content of Ca2+ in mitochondria prevents mitochondrial membrane swelling,
*HO-1↑, CAPE is beneficial as an antioxidant and the inductor of heme oxygenase-1 (HO), Nrf2-regulated gene
*NRF2↑,
*neuroP↑, HO-1 induction results in cardioprotective effects in diabetes [80], neuroprotective in microglial cells

2006- PLB,    Plumbagin induces apoptosis in human osteosarcoma through ROS generation, endoplasmic reticulum stress and mitochondrial apoptosis pathway
- in-vitro, OS, MG63 - in-vitro, Nor, hFOB1.19
tumCV↓, Plumbagin reduced cell viability in osteosarcoma cells but not normal bone cells
selectivity↑,
mtDam↑, Plumbagin induced cell apoptosis by mitochondrial dysfunction, which in turn promoted Ca2+ release and endoplasmic reticulum (ER)‑stress
Ca+2↓,
ER Stress↑,
ROS↑, plumbagin improved reactive oxygen species (ROS) generation
Casp3↑, apoptotic cascades activated caspase‑3 and caspase‑9 to elicit apoptosis response
Casp9↑,
Apoptosis↑,
eff↓, Moreover, plumbagin-induced apoptosis was reversed by pretreating with ROS scavenger N-acetyl cysteine (NAC), NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and H2O2 scavenging enzyme (catalase)

3342- QC,    Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells — up regulation of Nrf2 expression and down regulation of NF-κB and COX-2
- in-vitro, Nor, HepG2
*ROS↓, Pre-treatment with quercetin ameliorated ROS and calcium release as well as NF-κB induction and expression
*Ca+2↓,
*NF-kB↓,
*NRF2↑, Quercetin induced Nrf-2 nuclear translocation and expression.
*COX2↓, Quercetin's anti-inflammatory property was exhibited as it down regulated COX-2.
*Inflam↓,

3341- QC,    Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
*BioAv↑, Moreover, owing to its high solubility and bioavailability,
*GSH↑, Animal and cell studies found that quercetin induces GSH synthesis
*AChE↓, In this way, it has a stronger inhibitory effect against key enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are associated with oxidative properties
*BChE↓,
*H2O2↓, Quercetin has been shown to alleviate the decline of manganese-induced antioxidant enzyme activity, the increase of AChE activity, hydrogen peroxide generation, and lipid peroxidation levels in rats, thereby preventing manganese poisoning
*lipid-P↓,
*SOD↑, quercetin significantly enhanced the expression levels of endogenous antioxidant enzymes such as Cu/Zn SOD, Mn SOD, catalase (CAT), and GSH peroxidase in the hippocampal CA1 pyramidal neurons of animals suffering from ischemic injury.
*SOD2↑,
*Catalase↑,
*GPx↑,
*neuroP↑, Thus, quercetin may be a potential neuroprotective agent for transient ischemia
*HO-1↑, quercetin can promote fracture healing in smokers by removing free radicals and upregulating the expression of heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1, which protects primary human osteoblasts exposed to cigarette smoke
*cardioP↑, Quercetin has also been shown to prevent heart damage by clearing oxygen-free radicals caused by lipopolysaccharide (LPS)-induced endotoxemia.
*MDA↓, quercetin treatment increased the levels of SOD and CAT and reduced the level of MDA after LPS induction, suggesting that quercetin enhanced the antioxidant defense system
*NF-kB↓, quercetin promotes disease recovery by downregulating the expression of NIK and NF-κB including IKK and RelB, and upregulating the expression of TRAF3.
*IKKα↓,
*ROS↓, quercetin controls the development of atherosclerosis induced by a high-fructose diet by inhibiting ROS and enhancing PI3K/AKT.
*PI3K↑,
*Akt↑,
*hepatoP↑, Quercetin exerts antioxidant and hepatoprotective effects against acute liver injury in mice induced by tertiary butyl hydrogen peroxide. T
P53↑, Quercetin prevents cancer development by upregulating p53, which is the most common inactivated tumor suppressor. It also increases the expression of BAX, a downstream target of p53 and a key pro-apoptotic gene in HepG2 cells
BAX↑,
IGF-1R↓, Studies have found that insulin-like growth factor receptor 1 (IGFIR), AKT, androgen receptor (AR), and cell proliferation and anti-apoptotic proteins are increased in cancer, but quercetin supplementation normalizes their expression
Akt↓,
AR↓,
TumCP↓,
GSH↑, Moreover, quercetin significantly increases antioxidant enzyme levels, including GSH, SOD, and CAT, and inhibits lipid peroxides, thereby preventing skin cancer induced by 7,12-dimethyl Benz
SOD↑,
Catalase↑,
lipid-P↓,
*TNF-α↓, Heart: increases TNF-α, and prevents Ca2+ overload-induced myocardial cell injury
*Ca+2↓,

2467- RES,    Resveratrol inhibits Ca2+ signals and aggregation of platelets
- in-vitro, Nor, NA
*AntiAg↑, The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca2+ release from its stores and inhibiting store-operated Ca2+ influx into platelets.
Ca+2↓, Pretreatment of platelets with resveratrol (12.5 μM) attenuated the increase in [Ca2+]i in thrombin- or thapsigargin-stimulated platelets

3616- RosA,    Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders
- Review, AD, NA
*Inflam↓, worthy source for curing inflammation, analgesic, anti-anxiety, and memory boosting.
*memory↑,
*toxicity↓, Rosmarinic acid was observed to have very scarce toxicity with an LD50 of 561 mg/kg in mice
*ROS↓, Figure 1
*Catalase↑,
*SOD↑,
*NRF2↑,
*Aβ↓,
*AChE↓, decreased hippocampal AChE activity in bulbectomized mice.
*Ca+2↓,
*NO↓,
*IL2↓,
*COX2↓,
*PGE2↓,
*MMPs↓,
*TNF-α↓,
*iNOS↓,
*TLR4↓,
*cognitive↑, These cognitive-enhancing effects of rosmarinic acid might be beneficial to populations of advanced age
*cortisol↓, aroma of rosemary oil improved performance in exam students by enhancing free radical scavenging activity and decreasing cortisol levels
*lipid-P↓, Anti-oxidant components of rosemary extract (250, 500 and 750 mg/kg) reduced lipid peroxidation


Showing Research Papers: 1 to 50 of 61
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 61

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   CYP1A1↑, 1,   Ferroptosis↑, 2,   GPx↓, 1,   GPx↑, 1,   GPx4↓, 1,   GSH↓, 1,   GSH↑, 1,   H2O2↑, 1,   HO-1↑, 1,   Iron↑, 1,   lipid-P↓, 1,   lipid-P↑, 2,   MDA↑, 1,   NADPH/NADP+↓, 1,   NOX4↓, 1,   NRF2↑, 2,   OXPHOS↑, 1,   ROS↓, 2,   ROS↑, 9,   SOD↑, 1,  

Metal & Cofactor Biology ⓘ

FTH1↓, 1,   NCOA4↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   mitResp↓, 1,   MMP↓, 2,   mtDam↑, 3,   SDH↓, 1,  

Core Metabolism/Glycolysis ⓘ

ATG7↑, 1,   citrate↓, 1,   cMyc↓, 1,   CPT1A↓, 1,   FASN↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 5,   HK2↓, 2,   lactateProd↓, 1,   LAT↓, 1,   MCU↓, 1,   NAD↓, 1,   PDH↓, 1,   PDH↑, 1,   PDK1↓, 1,   p‑PDKs↓, 1,   PFK2?, 1,   PFKP↓, 1,   PKM2↓, 1,   PSMB5↓, 1,   Pyruv↓, 1,   TCA↓, 1,   β-oxidation↓, 1,  

Cell Death ⓘ

Akt↓, 6,   p‑Akt↓, 1,   Apoptosis↑, 6,   BAX↓, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Casp↑, 1,   Casp2↑, 1,   Casp3↑, 6,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 5,   Cyt‑c↑, 3,   Ferroptosis↑, 2,   GADD34↑, 1,   Mcl-1↓, 2,   PUMA↑, 1,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 2,  

Transcription & Epigenetics ⓘ

tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↓, 1,   eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   GRP94↑, 1,   IRE1∅, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 2,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 2,   p‑P53↑, 1,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   EMT↝, 1,   ERK↓, 1,   p‑GSK‐3β↓, 1,   IGF-1↓, 1,   IGF-1R↓, 2,   mTOR↓, 4,   p‑mTOR↓, 1,   PI3K↓, 2,   PTEN↑, 1,   STAT3↓, 1,   TumCG↓, 4,  

Migration ⓘ

Ca+2↓, 15,   Ca+2↑, 2,   i-Ca+2↓, 2,   i-Ca+2↑, 1,   CD38↑, 1,   Cdc42↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 1,   N-cadherin↓, 1,   Rho↓, 1,   TumCMig↓, 1,   TumCP↓, 5,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↑, 2,   Hif1a↓, 5,   VEGF↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   PGE2↓, 2,   PSA↓, 1,   T-Cell↝, 1,  

Cellular Microenvironment ⓘ

NOX↓, 1,   pH↑, 1,   i-pH↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose↓, 1,   Dose∅, 2,   eff↓, 4,   eff↑, 11,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

AR↓, 2,   Ki-67↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   chemoP↑, 1,   chemoPv↑, 1,   OS↑, 1,   Remission↑, 1,   Risk↓, 1,   toxicity↓, 1,   TumVol↓, 1,  
Total Targets: 149

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 12,   ARE↑, 1,   Bil↑, 2,   Catalase↓, 1,   Catalase↑, 8,   Fenton↓, 2,   GCLC↑, 2,   GCLM↑, 2,   GPx↓, 1,   GPx↑, 5,   GSH↑, 7,   H2O2↓, 1,   HO-1↑, 8,   lipid-P↓, 8,   MDA↓, 6,   MDA↑, 1,   NQO1↑, 3,   NRF2↑, 12,   ROS↓, 26,   ROS↑, 1,   mt-ROS↓, 1,   SIRT3↑, 2,   SOD↑, 13,   SOD2↑, 1,   TOS↓, 1,   Trx1↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 6,   MMP∅, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   ALAT↓, 2,   AMPK↓, 1,   AMPK↑, 1,   FASN↓, 1,   glucose↓, 1,   GlucoseCon↑, 1,   Glycolysis↑, 1,   LDH↓, 1,   MCU↓, 1,   PDH↑, 1,   PDKs↓, 1,   PPARα↝, 1,   PPARγ↑, 4,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↑, 1,   p‑Akt↑, 3,   Apoptosis↓, 4,   BAD↓, 2,   BAX↓, 4,   Bcl-2↑, 1,   Bcl-xL↑, 1,   Casp↓, 1,   Casp12↓, 1,   Casp3↓, 4,   cl‑Casp3↓, 1,   iNOS↓, 4,   JNK↓, 2,   MAPK↓, 2,   p‑MAPK?, 1,   p‑MAPK↓, 1,   p38↓, 1,   p38↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 3,   other?, 1,   other↝, 5,  

Protein Folding & ER Stress ⓘ

CHOP↓, 2,   ER Stress↓, 1,   GRP78/BiP↓, 2,   HSP70/HSPA5↑, 1,   IRE1↓, 1,   PERK↓, 1,   UPR↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 2,   p‑PARP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   ERK↑, 1,   p‑ERK↑, 1,   GSK‐3β↓, 1,   p‑mTOR↑, 1,   PI3K↑, 1,  

Migration ⓘ

AntiAg↑, 2,   APP↓, 2,   Ca+2↓, 30,   p‑Ca+2↓, 1,   i-Ca+2↓, 2,   mt-Ca+2↓, 1,   Ki-67↓, 1,   MMP2↑, 1,   MMP9↓, 1,   MMPs↓, 1,   ROCK1↓, 1,   TRPC1↓, 1,   VCAM-1↓, 3,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   HIF-1↓, 1,   Hif1a↓, 1,   Hif1a↑, 1,   NO↓, 4,   VEGF↑, 3,  

Barriers & Transport ⓘ

BBB↑, 4,   GLUT3↑, 1,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   ICAM-1↓, 3,   IKKα↓, 1,   IL1β↓, 4,   IL2↓, 1,   IL2↑, 1,   IL22↓, 1,   IL6↓, 3,   IL8↓, 2,   Inflam↓, 14,   NF-kB↓, 11,   p‑NF-kB↓, 1,   PGE2↓, 3,   TLR4↓, 3,   TNF-α↓, 14,  

Synaptic & Neurotransmission ⓘ

AChE↓, 5,   BChE↓, 1,   BDNF↑, 2,   ChAT↑, 3,   tau↓, 1,   p‑tau↓, 5,  

Protein Aggregation ⓘ

Aβ↓, 12,   BACE↓, 1,   NLRP3↓, 2,  

Hormonal & Nuclear Receptors ⓘ

cortisol↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 3,   Dose↑, 1,   Dose↝, 4,   eff↓, 1,   eff↑, 3,   Half-Life↝, 2,   P450↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   AST↓, 2,   Bil↑, 2,   BMD↑, 1,   BP↓, 1,   GutMicro↑, 2,   IL6↓, 3,   Ki-67↓, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   cardioP↑, 6,   cognitive↑, 11,   hepatoP↑, 7,   memory↑, 10,   motorD↑, 3,   neuroP↑, 15,   OS↑, 1,   radioP↑, 1,   RenoP↑, 1,   toxicity↓, 3,   toxicity∅, 1,  
Total Targets: 161

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
7 Boron
7 Taurine
6 Magnetic Fields
5 Citric Acid
4 EGCG (Epigallocatechin Gallate)
3 Berberine
2 Baicalein
2 Dichloroacetate
2 Ferulic acid
2 Hydrogen Gas
2 Honokiol
2 Quercetin
1 Anthocyanins
1 Alpha-Lipoic-Acid
1 Chlorogenic acid
1 Chocolate
1 Crocetin
1 Curcumin
1 Folic Acid, Vit B9
1 Lycopene
1 Magnetic Field Rotating
1 Moringa oleifera
1 Propolis -bee glue
1 Plumbagin
1 Resveratrol
1 Rosmarinic acid
1 salinomycin
1 Sulforaphane (mainly Broccoli)
1 Shikonin
1 Urolithin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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