PPARγ Cancer Research Results

PPARγ, Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG): Click to Expand ⟱
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Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a type of nuclear receptor that plays a crucial role in regulating various biological processes, including glucose metabolism, lipid metabolism, and inflammation. It is primarily expressed in adipose tissue, but it is also found in other tissues, including the colon, breast, and prostate.
PPAR-γ has been shown to have both tumor-suppressive and tumor-promoting effects, depending on the type of cancer and the context. In some cancers, activation of PPAR-γ can inhibit cell proliferation and induce apoptosis, while in others, it may promote tumor growth.
PPARγ
– Plays a central role in adipogenesis, lipid storage, and insulin sensitivity.
– Widely expressed in adipose tissue, but also present in colon, breast, and immune cells.
– In addition to metabolic functions, PPARγ regulates cell differentiation, apoptosis, and has anti-inflammatory effects.
– Ligand binding (such as endogenous fatty acids or synthetic agonists like thiazolidinediones) alters transcriptional programs impacting cell cycle and survival.

– In many cases, PPARγ is expressed in tumor cells, and its activation has been linked to induction of differentiation and growth arrest.
– However, expression levels can differ based on tumor subtype, with some studies reporting elevated levels while others note reductions in aggressive tumors.
– Crosstalk with other signaling pathways (e.g., Wnt/β-catenin, MAPK) can alter PPARγ's net effect in cancer cells.
Scientific Papers found: Click to Expand⟱
1253- aLinA,    The Antitumor Effects of α-Linolenic Acid
- Review, NA, NA
PPARγ↑,
COX2↓,
E6↓,
E7↓,
P53↑,
p‑ERK↓,
p38↓,
lipid-P↑,
ROS⇅, ALA could inhibit cancer by stimulating ROS production to induce apoptosis (other places implies reduced) appropriate dose of ALA can also reduce OS by regulating SOD, CAT, GPx, GSH, and NADPH oxidase
MPT↑, directly activate mitochondrial permeability transition
MMP↓,
Cyt‑c↑, cytochrome c (cyt c) release
Casp↑,
iNOS↓,
NO↓,
Casp3↑,
Bcl-2↓,
Hif1a↓,
FASN↓,
CRP↓,
IL6↓,
IL1β↓,
IFN-γ↓,
TNF-α↓,
Twist↓,
VEGF↓,
MMP2↓,
MMP9↓,

4280- Api,    Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms
- Review, AD, NA - Review, Park, NA
*neuroP↑, Apigenin, a flavonoid found in various herbs and plants, has garnered significant attention for its neuroprotective properties
*antiOx↑, shown to possess potent antioxidant activity, which is thought to play a crucial role in its neuroprotective effects
*ROS↓, Apigenin has been demonstrated to scavenge ROS, thereby reducing oxidative stress and mitigating the damage to neurons
*Inflam↓, apigenin has been found to possess anti-inflammatory properties.
*TNF-α↓, inhibit the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, which are elevated in neurodegenerative diseases
*IL1β↓,
*PI3K↑, apigenin has been shown to activate the PI3K/Akt signaling pathway, which is involved in promoting neuronal survival and preventing apoptosis.
*Akt↑,
*BBB↑, Apigenin has additional neuroprotective properties due to its ability to cross the BBB and enter the brain
*NRF2↑, figure 1
*SOD↑, pigenin has also been shown to activate various antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)
*GPx↑,
*MAPK↓, Apigenin inhibits the MAPK signalling system, which significantly reduces oxidative stress-induced damage in the brain
*Catalase↑, , including SOD, catalase, GPx and heme oxygenase-1 (HO-1) [37].
*HO-1↑,
*COX2↓, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*PGE2↓,
*PPARγ↑, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*TLR4↓,
*GSK‐3β↓, Apigenin can inhibit the activity of GSK-3β,
*Aβ↓, Inhibiting GSK-3 can reduce Aβ production and prevent neurofibrillary disorders.
*NLRP3↓, Apigenin suppresses nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation by upregulating PPAR-γ
*BDNF↑, Apigenin causes upregulation of BDNF and TrkB expression in several animal models
*TrkB↑,
*GABA↑, Apigenin enhances GABAergic signaling by increasing the frequency of chloride channel opening, leading to increased inhibitory neurotransmission
*AChE↓, It blocks acetylcholinesterase and increases acetylcholine availability.
*Ach↑,
*5HT↑, Apigenin has been shown to increase 5-HT levels, decrease 5-HT turnover, and prevent dopamine changes.
*cognitive↑, Apigenin increases the availability of acetylcholine in the synapse after inhibiting AChE, thereby enhancing cholinergic neurotransmission and improving cognitive function and memory
*MAOA↓, apigenin acts as a monoamine oxidase (MAO) inhibitor and MAO inhibitors increase the levels of monoamines in the brain

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

3675- Ash,    Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)
*memory↑, widely in Ayurvedic medicine as a nerve tonic and memory enhancer.
*neuroP↑, neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.
*Aβ↓, Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ)
*LDH↓, Ashwagandha treatment showed protective effects against the cytotoxicity as the levels of LDH leakage in Ashwagandha plus β-amyloid treated cultures were comparable with controls
*PPARγ↑, decreased PPARγ protein levels in β-amyloid treated and its reversal by Ashwagandha in SK-N-MC neuronal cells.
*cognitive↑, traditional medicine for cognitive and other HIV associated neurodegenerative disorders.

2615- Ba,    The Multifaceted Role of Baicalein in Cancer Management through Modulation of Cell Signalling Pathways
- Review, Var, NA
*AntiCan↓, Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation
*Inflam↓,
TumCP↓,
NF-kB↓, baicalein decreased the activation of nuclear factor-κB (NF-κB)
PPARγ↑, anti-inflammatory effects of baicalein might be initiated via PPARγ activation.
TumCCA↑, baicalein inhibited cell cycle progression and cell growth, and promoted apoptosis of cancer cells
JAK2↓, inactivation of the signaling pathway JAK2/STAT3 [63]
STAT3↓,
TumCMig↓, baicalein suppressed migration as well as invasion through decreasing the aerobic glycolysis and expression of MMP-2/9 proteins.
Glycolysis↓,
MMP2↓,
MMP9↓,
selectivity↑, Furthermore, baicalein and baicalin had less inhibitory effects on normal ovarian cells’ viability.
VEGF↓, baicalein is more effective in inhibiting the expressions of VEGF, HIF-1α, cMyc, and NFκB
Hif1a↓,
cMyc↓,
ChemoSen↑, baicalein enhanced the cisplatin sensitivity of SGC-7901/DDP gastric cancer cells by inducing autophagy and apoptosis through the Akt/mTOR and Keap 1/Nrf2 pathways
ROS↑, oral squamous cell carcinoma Cal27 cells. Significantly, it was noticed that baicalein activated reactive oxygen species (ROS) generation in Cal27 cells
p‑mTOR↓, results suggest that p-mTOR, p-Akt, p-IκB, and NF-κB protein expressions were decreased
PTEN↑, Baicalein upregulated PTEN expression, downregulated miR-424-3p, and downregulated PI3K and p-Akt.

3678- BBR,    Network pharmacology study on the mechanism of berberine in Alzheimer’s disease model
- Review, AD, NA
*APP↓, BBR were decreased in the mRNA and protein expression of APP and presenilin 1 while PPARG was increased with a reduction in the NF-κB pathway.
*PPARγ↑, upregulated PPARG with decreasing its downstream NF-ΚB pathway
*NF-kB↓,
*Aβ↓, BBR played a protective role in the AD mice model via blocking APP processing and amyloid plaque formation.
*cognitive↑, berberine significantly reduced amyloid accumulation and improved cognitive impairment in APP/PS1 mice
*antiOx↑, via anti-oxidative stress, anti-neuroinflammation, inhibition of neuronal cell apoptosis, etc
*Inflam↓,
*Apoptosis↓,
*BioAv↑, BBR was found to be metabolized to dihydro-berberine by intestinal bacteria, whose bioavailability was five times higher than that of BBR
*BioAv↝, oral bioavailability (OB, >30%),
*BBB↑, blood-brain barrier (BBB, >0.3)
*motorD↑, BBR treated 5×FAD mice ameliorated their behavior activity including in locomotor activity and cognitive function compared to control.
*NRF2↑, BBR enhanced cellular antioxidant capacity, regulated antioxidant-related pathways such as Nrf2 and HO-1, and thereby reduced oxidative stress damage
*HO-1↑,
*ROS↓,
*p‑Akt↑, BBR significantly increased the phosphorylation levels of AKT and ERK
*p‑ERK↑,

5859- CAP,    Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?
- Review, Var, NA
*TRPV1↑, the absorbed capsaicin activates its receptor TRPV1, which causes the rapid influx of sodium ions (Na+) and calcium (Ca2+) from the extracellular environment to the cell interior.
*Ca+2↑,
*Na+↑,
*UCPs↑, by increasing thermogenic gene expression such as uncoupling protein 1 (UCP-1), Sirtuin 1 (SIRT-1) [25] and peroxisome proliferator-activated receptor -γ (PPARγ) coactivator 1α (PGC-1α)
*SIRT1↑,
*PPARγ↑,
*Inflam↓, suppressing inflammatory responses, increasing lipid oxidation, inhibiting adipogenesis
*lipid-P↑,
*IL6↓, decreasing the expression of inflammatory biomarkers such as IL-6, TNF, and CCL-2, associated with NF-κB inactivation
*TNF-α↓,
*NF-kB↓,
*p‑Akt↑, Phosphorylation of Akt is also described after capsaicin treatment, which results in disruption of the NRF2/Keap complex and release of activated transcription factor NRF2
*NRF2↑,
*HO-1↑, triggers the transcription of heme-oxygenase1 genes, which are essential for heme degradation and prevention of oxidative damage
*ROS↑,
*GutMicro↑, It is suggested that regular treatment with capsaicin increases diversity in the gut microbiota and abundance of short-chain fatty acid (SCFA)-producing bacteria

1082- CAR,    Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression
- in-vitro, lymphoma, U937
COX2↓,
PPARα↑,
PPARγ↑,

5817- CBD,    COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells
- vitro+vivo, Lung, A549
AntiTum⇅, The antitumorigenic mechanism of cannabidiol is still controversial.
tumCV↓, cannabidiol elicited decreased viability associated with apoptosis.
Apoptosis↑,
eff↓, Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ.
COX2↑, Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle.
PPARγ↑,

3794- CUR,    Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities
- Review, AD, NA
*GSK‐3β↓, Firstly, curcumin can inhibit kinases, such as GSK-3β and Cyclin-Dependent Kinase 5 (Cdk5), that excessively phosphorylate Tau protein
*CDK5↓,
*p‑tau↓,
*IronCh↑, curcumin's metal ion chelating capability contributes to the reduction of free radicals
*ROS↓,
*HO-1↑, upregulating antioxidant enzymes including heme oxygenase 1 (HO-1), superoxide dismutase (SOD), catalase, and enzymes involved in the synthesis of endogenous antioxidants, specifically glutathione (GSH)
*SOD↑,
*Catalase↑,
*GSH↑,
*TNF-α↓, inhibiting the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12,
*IL6↓,
*IL12↓,
*NRF2↑, inducing the production of anti-inflammatory mediators including HO-1/NRF-2, PPARα-γ, and IL-4
*PPARγ↑,
*IL4↑,
*AChE↓, researchers have observed that curcumin can suppress AChE mRNA expression levels, effectively preventing the Cd-induced rise in AChE activity
*Dose↝, While curcumin directly interacts with AChE, its inhibitory activity remains weak (IC50 = 67.69 μM)
*GutMicro↑, curcumin's interaction with gut microbiota exhibits potential anti-AD properties.

123- CUR,    Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells
- in-vitro, Colon, LoVo - in-vitro, Colon, COLO205 - in-vitro, Pca, PC3 - in-vitro, Pca, 22Rv1
NF-kB↓, curcumin analog
ATF3↑, our study showed that ATF3 was up-regulated by curcumin in both LNCaP and C4-2B cells
HO-1↑, Our data confirmed the tumor-inhibitory effects of HMOX-1 gene in prostate cancer cells, which was up-regulated by curcumin treatment.
Wnt↓, Wnt, PIK3/AKT/mTOR, and NF-κB signaling pathways were primarily inhibited by curcumin treatment
Akt↓,
mTOR↓,
PTEN↑, and PTEN dependent cell cycle arrest and apoptosis pathways were found to be elevated.
Apoptosis↑,
TGF-β↓, TGF-β signaling pathway was inhibited by curcumin treatment in androgen-dependent and independent manners.
PPARγ↑, Curcumin was also shown to induce PPAR-γ gene expression and inhibit hepatic stellate cell (HSC) activation by interrupting TGF-β signaling in vitro

13- CUR,    Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action
- Review, BC, NA
P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

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

4003- Gins,    Neuroprotective Potentials of Panax Ginseng Against Alzheimer's Disease: A Review of Preclinical and Clinical Evidences
- Review, adrenal, NA
*neuroP↑, has neuroprotective effects against a series of pathological cascades in AD, including beta-amyloid formation, neuroinflammation, oxidative stress, and mitochondrial dysfunction.
*Inflam↓,
*ROS↓,
*BACE↓, Ginsenoside Re inhibits the activity of BACE1 by increasing PPARγ expression at the mRNA and protein levels in N2a/APP695 cells and thereby reduces the generation of Aβ1–40 and Aβ1–42
*PPARγ↑,
*Aβ↓, ginsenosides Rb1, Rd, Re, and Rg1 can inhibit Aβ aggregation to regulate the phosphorylation of tau protein in the prevention and treatment of AD.
*p‑tau↓, inhibiting tau phosphorylation
*NF-kB↓, Rd pretreatment at 10 mg/kg significantly suppresses the NF-κB pathway activity, reducing the generation of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)
*IL1β↓,
*IL6↓,
*TNF-α↓,
*ROS↓, Ginsenoside Rg1 can reduce the NADPH oxidase 2 (NOX2)–mediated ROS production and neuronal apoptosis
*CREB↓, Ginsenoside F1 can decrease phosphorylated cAMP-response element binding protein (CREB) and increase cortical BDNF levels in the hippocampus, reducing Aβ plaques and improving memory function of APP/PS1 double-transgenic AD mice
*BDNF↑,
*memory↑,

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↑,

2901- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
*mitResp↑, mice treated with Honokiol showed enhanced mitochondrial respiration
*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat cardiomyocytes
*Inflam↓, Honokiol repressed cardiac inflammatory responses and oxidative stress in mice subjected to Dox treatment.
*ROS↓,
*cardioP↑, We conclude that Honokiol protects the heart from Dox-cardiotoxicity
*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice
*LDH↓, Furthermore, Honokiol treatment reduced the Dox-induced elevation of lactate dehydrogenase (LDH) activity (Fig. 6D) in mice subjected to acute Dox treatment.

2893- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
*mitResp↑, Oxygen consumption in freshly isolated mitochondria from mice treated with Honokiol showed enhanced mitochondrial respiration.
*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat
*cardioP↑, Honokiol alleviated Dox-cardiotoxicity with improved cardiac function and reduced cardiomyocyte apoptosis
*SIRT3↑, recent study reported that Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial SIRT3
*ROS↓, Honokiol treatment depressed total ROS levels, which illustrated by the less pronounced decreased ratio of GSH/GSSG in mice
*GSH↑,
*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice

2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp↓, The expres- sion of P-gp at mRNA and protein levels is reduced in HNK treatment on human MDR and MCF-7/ADR breast cancer cell lines

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

3277- Lyco,    Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent
- Review, Var, NA
antiOx↑, lycopene provides a strong antioxidant activity that is 100 times more effective than α-tocopherol and more than double effective that of β-carotene
TumCP↓, In vivo and in vitro experiments have demonstrated that lycopene at near physiological levels (0.5−2 μM) could inhibit cancer cell proliferation [[22], [23], [24]], induce apoptosis [[25], [26], [27]], and suppress metastasis [
Apoptosis↑,
TumMeta↑,
ChemoSen↑, lycopene can increase the effect of anti-cancer drugs (including adriamycin, cisplatin, docetaxel and paclitaxel) on cancer cell growth and reduce tumour size
BioAv↓, low water solubility and bioavailability of lycopene
Dose↝, The concentration of lycopene in plasma (daily intake of 10 mg lycopene) is approximately 0.52−0.6 μM
BioAv↓, significant decrease in lycopene bioavailability in the elderly
BioAv↑, oils and fats favours the bioavailability of lycopene [80], while large molecules such as pectin can hinder the absorption of lycopene in the small intestine due to their action on lipids and bile salt molecules
SOD↑, GC: 50−150 mg/kg BW/day ↑SOD, CAT, GPx ↑IL-2, IL-4, IL-10, TNF-α ↑IgA, IgG, IgM ↓IL-6
Catalase↑,
GPx↑,
IL2↑, lycopene treatment significantly enhanced blood IL-2, IL-4, IL-10, TNF-α levels and reduced IL-6 level in a dose-dependent manner.
IL4↑,
IL1↑,
TNF-α↑,
GSH↑, GC: ↑GSH, GPx, GST, GR
GPx↑,
GSTA1↑,
GSR↑,
PPARγ↑, ↑GPx, SOD, MDA ↑PPARγ, caspase-3 ↓NF-κB, COX-2
Casp3↑,
NF-kB↓,
COX2↓,
Bcl-2↑, AGS cells Lycopene 5 μM ↑Bcl-2 ↓Bax, Bax/Bcl-2, p53 ↓Chk1, Chk2, γ-H2AX, DNA damage ↓ROS Phase arrest
BAX↓,
P53↓,
CHK1↓,
Chk2↓,
γH2AX↓,
DNAdam↓,
ROS↓,
P21↑, CRC: ↑p21 ↓PCNA, β-catenin ↓COX-2, PGE2, ERK1/2 phosphorylated
PCNA↓,
β-catenin/ZEB1↓,
PGE2↓,
ERK↓,
cMyc↓, AGS cells: ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS
cycE/CCNE↓,
JAK1↓,
STAT3↓,
SIRT1↑, Huh7: ↑SIRT1 ↓Cells growth ↑PARP cleavage ↓Cyclin D1, TNFα, IL-6, NF-κB, p65, STAT3, Akt activation ↓Tumour multiplicity, volume
cl‑PARP↑,
cycD1/CCND1↓,
TNF-α↓,
IL6↓,
p65↓,
MMP2↓, SK-Hep1 human hepatoma cells Lycopene 5, 10 μM ↓MMP-2, MMP-9 ↓
MMP9↓,
Wnt↓, AGS cells Lycopene 0.5 μM, 1 μM ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS

1708- Lyco,    The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies
- Review, Var, NA
OS↑, reduced prostate cancer-specific mortality in men at high risk for prostate cancer
ChemoSen↑, improved the response to docetaxel chemotherapy in advanced castrate-resistant prostate cancer
QoL↑, lycopene improved the quality of life, and provided relief from bone pain and control of lower urinary tract symptoms
PSA∅, PSA stabilisation in prostate cancer
eff↑, Lycopene co-supplementation with vitamin E also showed an improvement in the results of prostate cancer treatment
AntiCan↑, lycopene intake showed a strong protective effect against stomach cancer, regardless of H. pylori status
AntiCan↑, A lycopene-rich diet was shown to reduce the incidence of pancreatic cancer in humans by 31%
angioG↓,
VEGF↓,
Hif1a↓,
SOD↑,
Catalase↑,
GPx↑,
GSH↑,
GPx↑,
GR↑,
MDA↓,
NRF2↑,
HO-1↑,
COX2↓,
PGE2↓,
NF-kB↓,
IL4↑,
IL10↑,
IL6↓,
TNF-α↓,
PPARγ↑,
TumCCA↑, G(0)/G(1) phase
FOXO3↓,
Casp3↑,
IGF-1↓, breast cancer,crc
p27↑,
STAT3↓,
CDK2↓,
CDK4↓,
P21↑,
PCNA↓,
MMP7↓,
MMP9↓,

4791- Lyco,    Investigating into anti-cancer potential of lycopene: Molecular targets
- Review, Var, NA
*antiOx↑, Lycopene, the main pigment of tomatoes, possess the strongest antioxidant activity among carotenoids. Lycopene has unique structure and chemical properties.
TumCP↓, the anticancer of lycopene is also considered to be an important determinant of tumor development including the inhibition of cell proliferation, inhibition of cell cycle progression, induction of apoptosis, inhibition of cell invasion, angiogenesis
TumCCA↓,
Apoptosis↑,
TumCI↓,
angioG↓,
TumMeta↓,
*Risk↓, and may be associated with a decreased risk of different types of cancer.
cycD1/CCND1↓, Several studies suggested lycopene decreased cell cycle related proteins, such as cyclin D1, D3 and E, the cyclin-dependent kinases 2 and 4, bcl-2, while decreased phospho-Akt levels and increased p21, p27, p53 and bax levels and in Bax: Bcl-2 ratio
CycD3↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
Bcl-2↓,
P21↑,
p27↑,
P53↑,
BAX↑,
selectivity↑, lycopene selectively inhibited cell growth in MCF-7 human breast cancer cells but not in the MCF-10 mammary epithelial cells
MMP↓, When treating LNCaP human prostate cancer cells with lycopene, the decreased mitochondrial function could be observed.
Cyt‑c↑, release of mitochondrial cytochrome c and finally led to apoptosis
Wnt↓, Lycopene could inhibit Wnt-TCF signaling pathway in cancer cells.
eff↑, Lycopene could synergistically increase QC anticancer activity and inhibit Wnt-TCF signaling in cancer cells.
PPARγ↑, Lycopene could inhibit the growth of cancer cells by activating the PPARγ – LXRα - ABCA1 pathway and decreasing cellular total cholesterol levels
LDL↓,
Akt↓, Lycopene suppressed Akt activation and non-phosphorylated β-Catenin,
PI3K↓, inhibited the proliferation of colon cancer HT-29 cells, which was associated with suppressing PI3K/Akt/mTOR signaling pathway
mTOR↓,
PDGF↓, Lycopene, however, could inhibit PDGF-BB-induced signaling and cell migration in both human cultured skin fibroblasts and melanoma-derived fibroblasts
NF-kB↓, anticancer properties of lycopene may occur to play its role through the inhibition of the NF-κB signaling pathway
eff↑, lycopene increased the sensitization of cervical cancer cells to cisplatin via the suppression of NF-κB-mediated inflammatory responses, and the modulation of Nrf2-mediated oxidative stress

5252- MAG,    Insights on the Multifunctional Activities of Magnolol
- Review, Var, NA
BioAv↓, However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application.
*Inflam↓, biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.
*Bacteria↓,
*antiOx↑,
*neuroP↑,
*cardioP↑,
CYP1A1↓, Magnolol isreported to inhibit the activity of CYP1A with an IC50value of 1.62 𝜇M,
*PPARγ↑, greatly upregulate the expression of PPAR𝛾 and suppress the expression of NF-𝜅B signaling, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and the production of ROS in bronchoalveolar lavage fluid
*NF-kB↓,
*COX2↓,
*iNOS↓,
*ROS↓,
Apoptosis↑, Pretreatment of combina-tion of magnolol with honokiol significantly decreases cellviability and proliferation and increases cell apoptosis
TumCCA↑, Magnolol at lower doses can cause cell cycle arrest atG0/G1 phase, decrease the expression of cyclin D1, cyclin A,and CDK2, and increase the expression of p21
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
P21↑,
TumCG↓, magnolol significantly inhibits cell growth,migration, and invasion, accompanied by decreased expres-sion of Ki67, proliferating cell nuclear antigen (PCNA),matrix metalloproteinases 2 (MMP-2),
TumCMig↓,
TumCI↓,
Ki-67↓,
PCNA↓,
MMP2↓,
MMP9↓,
MMP7↓,
DNAdam↑, In nonsmall cell lung cancer A549, H441, and H520 celllines (NSCLC), magnolol selectively induces DNA fragmen-tation, decreases mitochondrial membrane potential (Δ𝜓m),and inhibits cell proliferation
MMP↓,
TumCP↓,
selectivity↑, However, there is no obvious cytotoxicity of magnololto normal human bronchial epithelial cells.
PI3K↓, magnolol activates the expression of p38 and JNK and attenuates the activity of PI3K/Akt and ERK1/2 in A549 cells [
Akt↓,
H2O2↓, magnolol decreases the production of H2O2 and the expression of HIF-1𝛼 and increases the degradationof HIF-1𝛼.
Hif1a↓,
*BDNF↑, neurotrophic factor (BDNF) and glial fibrillary acidic protein(GFAP) are downregulated ... effectively reverses the effects
*NRF2↑, Magnolol inhibits NF-𝜅B and MAPK signaling pathways and apoptosis and activates NRF2/KEAP1
*AChE↑, table 1

193- MFrot,  MF,    Rotating Magnetic Field Mitigates Ankylosing Spondylitis Targeting Osteocytes and Chondrocytes via Ameliorating Immune Dysfunctions
- in-vivo, Arthritis, NA
BMD↑, loss reduced
Cartilage↑, more intact cartilage surfaces and denser proteoglycan
IL17↓,
IL22↓,
IL23↓,
IL28↓,
CD4+↓, tremendously attenuated
CD8+↓, In this investigation, data showed that RMF treatment decreased CD3-expressing proliferative cells via immunostaining and reduced CD4+/CD8+ T-cells via flow cytometry in AS mice
LAMB3↑,
COL4↓,
THBS2↓,
ITGA11↓,
PPARγ↑, mice have decreased expression of peroxisome proliferator-activated receptor γ (PPAR-γ), a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily, which RMF reverses.
ACAA1↓,
PLIN1↓,
FABP4↓,
PCK1↓,
UCP1↓,
TNF-α↓,

4643- OLE,  HT,    Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine
- Review, Var, NA
TumCCA↑, A similar S phase cell cycle arrest was also observed for 800 μM HT, and induction of apoptosis also took place after 24 h incubation of HT-29 cells with 600 μM and 800 μM HT
Apoptosis↑,
ER Stress↑, 400 μM HT triggered endoplasmic reticulum stress in HT-29 cells, with activation of unfolded protein response,
UPR↑,
CHOP↑, increase in CHOP protein levels (responsible for ROS production and Bcl-2 downregulation) and NADPH oxidase 4 (NOX4)
ROS↑,
Bcl-2↓,
NOX4↑,
Hif1a↓, Moreover, 400 μM HT reduced HIF-1α protein levels
MMP2↓, figure 2
MMP↓,
VEGF↓,
Akt↓,
NF-kB↓,
p65↓,
SIRT3↓,
mTOR↓,
Catalase↓,
SOD2↓,
FASN↓,
STAT3↓,
HDAC2↓,
HDAC3↓,
BAD↑, figure 2 upregulated
BAX↑,
Bak↑,
Casp3↑,
Casp9↑,
PARP↑,
P53↑,
P21↑,
p27↑,
Half-Life↝, HT added to extra virgin olive oil produced a plasma peak of 3.79 ng/mL after 30 min, followed by a rapid decline in HT plasma concentration
BioAv↓, On the basis of these pieces of data, it becomes evident that cytotoxicity and anti-cancer effects of OLE and HT were recorded at concentrations largely exceeding those reachable with diet/olive oil consumption
BioAv↓, Thus, it is difficult to imagine how OLE and HT may be used as cancer-preventive/treating agents if the route of administration is ingestion.
selectivity↑, However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells,
RadioS↑, 200 μM OLE enhanced cell radiosensitivity in vitro and in vivo after injection in BALB/C nude mice
*ROS↓, A lot of experimental data in vivo and in vitro have definitively demonstrated the ROS scavenger ability of OLE and HT, which can also act on antioxidant cellular mechanisms restoring ROS homeostasis,
*GSH↑, including promotion of the increase in reduced glutathione levels (GSH), depletion of lipid peroxidation product malondialdehyde (MDA), intensification of the expression and/or activity of detoxicating enzymes SOD, CAT, glutathione-S-transferase (GST
*MDA↓,
*SOD↑,
*Catalase↑,
*NRF2↑, and nuclear factor E2-related factor 2 (Nrf2) upregulation/transactivation,
*chemoP↑, OLE and HT have shown an important ability to mitigate the toxicity elicited by chemotherapeutic agents mainly through their largely demonstrated antioxidant and ROS scavenger activity.
*Inflam↓, OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models,
PPARγ↑, HT-dependent anti-inflammatory effect was also mediated by HT-elicited increase in protein levels of PPARγ

3587- PI,    Piperine: A review of its biological effects
- Review, Park, NA - Review, AD, NA
*hepatoP↑, piperine has also been documented for its hepatoprotective, anti-allergic, anti-inflammatory, and neuroprotective properties
*Inflam↓,
*neuroP↑,
*antiOx↑, antiangiogenesis, antioxidant, antidiabetic, antiobesity, cardioprotective,
*angioG↑,
*cardioP↑,
*BioAv↑, nano-encapsulation and resulting piperine-loaded nanoparticles enhance the bioavailability of piperine via oral administration
*P450↓, piperine inactivates cytochrome P450 (CYP) 3A (CYP3A), which plays a critical role in drug metabolism
*eff↑, enhances the anti-inflammatory effects when combined with resvera- trol
*BioAv↑, piperine increases the bioavailability of various compounds such as ciprofloxacin, norfloxacin, metronidazole, oxytetracycline, nimesulide, pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin, gallic acid, tiferron, nevirapine, and sparte
E-cadherin↓, Downregulates the E-cadherin (E-cad), estrogen receptor (ER), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP- 9), vascular endothelial growth factor (VEGF) levels, and c-Myc.
ER(estro)↓,
MMP2↓,
MMP9↓,
VEGF↓,
cMyc↓,
BAX↑, Increases the expressions of Bax and p53.
P53↑,
TumCG↓, Lowers the tumor growth and elevates survival time
OS↑,
*cognitive↑, piperine ameliorated the neuro-chemical, neuroinflammatory, and cognitive alterations caused by chronic exposure to galactose
*GSK‐3β↓, piperine reversed D-Gal-induced GSK-3β activation through modulating PKC and PI3K/AKT pathways, s
*GSH↑, Piperine stimulates glutathione levels in rats' striatum, reduced caspase-3 and 9 activation, and diminished release of cytochrome-c from mitochondria along with a reduction in lipid peroxidation
*Casp3↓,
*Casp9↓,
*Cyt‑c↓,
*lipid-P↓,
*motorD↑, piperine also caused improvement in motor coordination and balance behavior along with reduction in contralateral rotations.
*AChE↓, significantly amended impaired memory and hippo-campus neurodegeneration and lowered lipid peroxidation and acetylcholinesterase enzyme
*memory↑,
*cardioP↑,
*ROS↓, fig 6
*PPARγ↑,
*ALAT↓, piperine lowers alanine aminotransferase (ALT), AST, and ALP levels in sera of cholesterol-fed albino mice
*AST↓,
*ALP↓,
*AMPK↑, reversed the downregulation of AMPK signaling molecules, which are responsible for fatty acid oxidation, insulin signaling, and lipogenesis in mouse liver.
*5HT↑, t causes a significant decrease in serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) contents in the hippocampus and frontal cortex.
*SIRT1↑, , it may enhance the SIRT1 expression in cells and SIRT1 activity enhancing its potential to prevent SIRT1-mediated disease
*eff↑, combination ther- apy of resveratrol and piperine as an approach to enhance the biologi- cal effects with respect to cerebral blood flow and improved cognitive functions

49- QC,    Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-γ expression in human A549 lung cancer cells
- in-vitro, Lung, A549
CDK1↓, significantly suppressed the effects of 10 % QMP on cell proliferation and on the expression of cyclin B and cdk1. T
CycB/CCNB1↓,
PPARγ↑, activation of PPAR- γ plays an important role, at least in part, in the antiproliferative effects of quercetin metabolites.

2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, comprehensive overview of resveratrol's neuroprotective role in IS
*NRF2↑, Findings from previous studies suggest that Nrf2 activation can significantly reduce brain injury following IS and lead to better outcomes
*SIRT1↑, neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways.
*PGC-1α↑, IRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO)
*FOXO↑,
*HO-1↑, ctivation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic bra
*NQO1↑,
*ROS↓,
*BP↓, Multiple studies have demonstrated that resveratrol presented protective effects in IS, it can mediate blood pressure and lipid profiles which are the main key factors in managing and preventing stroke
*BioAv↓, The residual quantity of resveratrol undergoes metabolism, with the maximum reported concentration of free resveratrol being 1.7–1.9 %
*Half-Life↝, The levels of resveratrol peak 60 min following ingestion. Another study found that within 6 h, there was a further rise in resveratrol levels. This increase can be attributed to intestinal recirculation of metabolites
*AMPK↑, Resveratrol also increases AMPK and inhibits GSK-3β (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces ROS
*GSK‐3β↓,
*eff↑, Furthermore, oligodendrocyte survival is boosted by resveratrol, which may help to preserve brain homeostasis following a stroke
*AntiAg↑, resveratrol may suppress platelet activation and aggregation caused by collagen, adenosine diphosphate, and thrombin
*BBB↓, Although resveratrol is a highly hydrophobic molecule, it is exceedingly difficult to penetrate a membrane like the BBB. However, an alternate administration is through the nasal cavity in the olfactory area, which results in a more pleasant route
*Inflam↓, Resveratrol's anti-inflammatory effects have been demonstrated in many studies
*MPO↓, Resveratrol dramatically lowered the amounts of cerebral infarcts, neuronal damage, MPO activity, and evans blue (EB) content in addition to neurological impairment scores.
*TLR4↓, TLR4, NF-κB p65, COX-2, MMP-9, TNF-α, and IL-1β all had greater levels of expression after cerebral ischemia, whereas resveratrol decreased these amounts
*NF-kB↓,
*p65↓,
*MMP9↓,
*TNF-α↓,
*IL1β↓,
*PPARγ↑, Previous studies have shown that resveratrol activates the PPAR -γ coactivator 1α (PGC-1 α), which has free radical scavenging properties
*MMP↑, Resveratrol can prevent mitochondrial membrane depolarization, preserve adenosine triphosphate (ATP) production, and inhibit the release of cytochrome c
*ATP↑,
*Cyt‑c∅,
*mt-lipid-P↓, mitochondrial lipid peroxidation (LPO), protein carbonyl, and intracellular hydrogen peroxide (H2O2) content were significantly reduced in the resveratrol treatment group, while the expression of HSP70 and metallothionein were restored
*H2O2↓,
*HSP70/HSPA5↝,
*Mets↝,
*eff↑, Shin et al. showed that 5 mg/kg intravenous (IV) resveratrol reduced infarction volume by 36 % in an MCAO mouse model.
*eff↑, This study indicates that resveratrol holds the potential to improve stroke outcomes before ischemia as a pre-treatment strategy
*motorD↑, resveratrol treatment significantly reduced infarct volume and prevented motor impairment, increased glutathione, and decreased MDA levels compared to the control group,
*MDA↓,
*NADH:NAD↑, Resveratrol treatment significantly enhanced the intracellular NAD+/NADH ratio
eff↑, Pretreatment with resveratrol (20 or 40 mg/kg) significantly lowered the cerebral edema, infarct volume, lipid peroxidation products, and inflammatory markers
eff↑, Intraperitoneal administration of resveratrol at a dose of 50 mg/kg reduced cerebral ischemia reperfusion damage, brain edema, and BBB malfunction

3100- RES,    Neuroprotective effects of resveratrol in Alzheimer disease pathology
- Review, AD, NA
*neuroP↑, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol
*BioAv↓, However, resveratrol’s low bioavailability originating from its poor water solubility and resulting from its short biological half-life
*Half-Life↓,
*BioAv↑, encapsulation in liposomal formulations
*BBB↑, Resveratrol being a lipophilic compound can readily cross the BBB via transmembrane diffusion
*NRF2↑, resveratrol into aged cells leading to the activation of cellular Nrf2-mediated antioxidant defense systems
*BioAv↓, An oral dose of 25 mg results in less than 5 μg/mL in the serum following absorption through the gastrointestinal tract, corresponding to approximately a 1000-fold decrease in bioavailability.
*BioAv↑, Treatment with pterostilbene also produced a sevenfold rise in its oral bioavailability than the parent resveratrol
*SIRT1↑, Amongst all the naturally occurring activators of SIRT 1, resveratrol is considered to be the most effective SIRT 1 activator.
*cognitive↑, Pterostilbene has shown to be a potent modulator of cognition and cellular oxidative stress associated with AD
*lipid-P↓, Figure 2
*HO-1↑,
*SOD↑,
*GSH↑,
*GPx↑,
*G6PD↑,
*PPARγ↑,
*AMPK↑,
*Aβ↓, Lowered Aβ levels by activating AMPK pathway

3010- RosA,    Exploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation
- in-vitro, Lung, A549 - in-vivo, NA, NA
TumCG↓, RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells.
Ki-67↓,
FABP4↑, Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells.
PPARα↑,
ROS↑, RosA increases ROS levels in lung tumor tissues and induces apoptosis
Apoptosis↑,
MMP9↓, In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells.
IGFBP3↓,
MMP2↓, In addition, RosA down-regulated the expression of MMP-9 and MMP2, regulated epithelial-mesenchymal transition to inhibit cell invasion, and slow down tumor development.
EMT↓,
TumCI↓,
PI3K↓, his study also confirmed that RosA down-regulated the expression of the PI3K/AKT/mTOR pathway-related proteins
Akt↓,
mTOR↓,
Gli1↓, Xiang Zhou et al. [28] reported that RosA inhibited the growth of PDAC tumors by inhibiting Gli1.
PPARγ↑, Upregulated expression of PPARG
Cyt‑c↑, figure 7

4190- Sesame,    Sesame Seeds: A Nutrient-Rich Superfood
- Review, NA, NA
*antiOx↑, esame oil has been shown to have antioxidant and health-promoting benefits due to its high concentration of tocopherol, phytosterol, lignan, and other components
*LDL↓, sesame oil can reduce levels of low-density lipoprotein (LDL) and decrease the risk of atherosclerosis and cardiovascular diseases.
*Aβ↓, Alzheimer’s disease is linked to the deposition of toxic cellular amyloid proteins, and the prolonged consumption of sesamol may efficiently hinder this buildup
*TNF-α↓, Figure 2
*SOD↑,
*SIRT1↑,
*Catalase↑,
*GSH↑,
*MDA↓,
*GSTs↑,
*IL4↑,
*GPx↑,
*COX2↓,
*PGE2↓,
*NO↓,
CDK2↑,
COX2↑,
MMP9↑,
ICAM-1↓,
*BDNF↑, sesame oil increased brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor gamma (PPAR-γ) levels.
*PPARγ↑,
*AChE↓, figure 2
*Inflam↓, potent antioxidant properties, which may contribute to its anti-inflammatory effects.
*HO-1↑, activation of HO-1, leading to the inhibition of the IKKα/NFκB pathway, recognized for its involvement in inflammatory processes
*NF-kB↓,
*ROS↓, sesamin was found to decrease oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS), and increase the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).

3648- SIL,    Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years
- Review, NA, NA
*antiOx↑, antioxidant, anti-inflammatory and antifibrotic power
*Inflam↓,
*lipid-P↓, reduce both lipid peroxidation and cellular necrosis.
*necrosis↓,
*hepatoP↑, silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
*IL1↓, figure 1
*IL6↓,
*TNF-α↓,
*IFN-γ↓,
MAPK↓,
Apoptosis↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
*PPARγ↑,
*GLUT4↑,
*HSPs↓,
*HSP27↑,
*Trx↑,
*SIRT1↑,
*ALAT↓, as well as prevent ALT increase, Glutathione (GSH) decrease, lipid peroxidation and TNF-α increase
*GSH↑,
*lipid-P↓,
*TNF-α↓,
TumCG↓, silybin significantly reduces HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells growth by increasing cyclin-dependent kinase inhibitor p21 and p27/cyclin-dependent kinase (CDK) 4 complexes, by reducing retinoblastoma protein (Rb)-phosphorylatio
P21↑,
CDK4↑,

2124- TQ,    Thymoquinone: an emerging natural drug with a wide range of medical applications
- Review, Var, NA
hepatoP↑, Hepatoprotective
Bax:Bcl2↑, A549 non-small cell lung cancer cells exposed to benzo(a)pyrene plus TQ in vitro
cycD1/CCND1↓,
P21↑,
TRAIL↑,
P53↑,
TumCCA↑, G2/M cell cycle arrest
hepatoP↑, Hepatoprotective effects
*ALAT↓, The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tissue levels of malondialdehyde (MDA), oxidized glutathione (GSSG), and superoxide dismutase (SOD) activity were found to be lower
*AST↓,
*MDA↓,
*GSSG↓,
*COX2↓, N. sativa and TQ treatment also suppressed the expression of the COX-2 enzyme in the pancreatic tissue
*lipid-P↓, Thymoquinone and thymohydroquinone inhibited in vitro non-enzymatic lipid peroxidation in hippocampal homogenates induced by iron-ascorbate (52)
PPARγ↑, In breast cancer cells TQ was able to increase peroxisome proliferator-activated receptor gamma (PPAR-γ) activity
p38↑, Treatment of human breast carcinoma in both in vitro and in vivo models demonstrated antiproliferative and proapoptotic effects of TQ, which are mediated by its inductive effect on p38 and ROS signaling
ROS↑,
ChemoSen↑, TQ possesses anti-tumor effects in breast tumor xenograft mice and it potentiates the antitumor effect of doxorubicin (64).
selectivity↑, TQ is also a microtubule-targeting agent (MTA), and binds to the tubulin-microtubule network, thus preventing microtubule polymerization and causing mitotic arrest and apoptosis of A549 cells but not of normal HUVEC cells
selectivity↑, No effect on α/β tubulin protein expression was found in normal human fibroblasts used as control cell model. These data indicate that TQ exerts a selective effect on α/β tubulin in cancer cells
*MDA↓, Reduction of tissue MDA levels, and increased SOD levels
*SOD↑,

3426- TQ,    Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms
- in-vitro, BC, MDA-MB-468 - in-vitro, AML, JK
UHRF1↓, (UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells
DNMT1↓,
DNMT3A↓,
DNMTs↓,
HDAC1↓,
HDAC4↓,
HDAC↓,
DLC1↑, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated,
PPARγ↑,
FOXO↑,
TET2↑,
CYP1B1↑,
G9a↓, expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose

3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

3564- TQ,    The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights
- in-vivo, AD, NA
*Inflam↓, Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics.
*AntiCan↑,
*antiOx↑,
*neuroP↑, TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity.
*cognitive↑, TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes,
*Aβ↓, significant decrease in the deposition of amyloid beta (Aβ).
*PPARγ↑, TQ showed a significant upregulation for PPAR-γ, synapsin-2, and miR-9
*NF-kB↓, pretreatment of the mice with TQ significantly (p < 0.001) lowered NF-κB by 62.68%
*p‑tau↓, TQ significantly (p < 0.001) decreased Ptau by 58.33% relatively to the disease control group
*MMP↑, Pretreatment with TQ restored the mitochondrial membrane potential (MMP)
*memory↑, Poorgholam et al. (2018), who elucidated that TQ ameliorated learning functioning and memory loss in a rat model of AD
*NF-kB↓, inhibitory effect of TQ on the activation of NF-κB
*ROS↓, TQ may possess neuroprotective properties hampering the mitochondrial membrane depolarization, ROS generation, and Aβ deposition in neurotoxicity model


Showing Research Papers: 1 to 38 of 38

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 38

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ATF3↑, 1,   Catalase↓, 1,   Catalase↑, 2,   CYP1A1↓, 1,   GPx↑, 4,   GSH↑, 2,   GSR↑, 1,   GSTA1↑, 1,   H2O2↓, 1,   HO-1↓, 1,   HO-1↑, 2,   lipid-P↑, 1,   MDA↓, 1,   NOX4↑, 1,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 5,   ROS⇅, 2,   SIRT3↓, 1,   SOD↑, 2,   SOD2↓, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   MMP↓, 4,   MPT↑, 1,   OCR↑, 1,   UCP1↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACAA1↓, 1,   AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 3,   ECAR↓, 1,   FABP4↓, 1,   FABP4↑, 1,   FASN↓, 2,   GlucoseCon↓, 1,   Glycolysis↓, 2,   IR↓, 1,   lactateProd↓, 1,   LDL↓, 1,   PCK1↓, 1,   PKM2↓, 1,   PLIN1↓, 1,   PPARα↑, 2,   PPARγ↑, 17,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 8,   Apoptosis↑, 9,   BAD↑, 1,   Bak↑, 1,   BAX↓, 1,   BAX↑, 3,   Bax:Bcl2↑, 1,   Bcl-2↓, 5,   Bcl-2↑, 1,   BID↓, 1,   Casp↑, 1,   Casp3↑, 6,   Casp8↑, 1,   Casp9↑, 3,   cFLIP↓, 1,   Chk2↓, 1,   Cyt‑c↑, 5,   DR5↑, 3,   FADD↑, 1,   Fas↑, 3,   iNOS↓, 2,   JNK↑, 3,   MAPK↓, 2,   MAPK↑, 1,   Mcl-1↓, 2,   Myc↓, 1,   p27↑, 5,   p38↓, 1,   p38↑, 3,   survivin↓, 1,   TRAIL↑, 2,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   PAK↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↓, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   CYP1B1↑, 2,   DNAdam↓, 1,   DNAdam↑, 1,   DNMT1↓, 2,   DNMT3A↓, 1,   DNMTs↓, 1,   G9a↓, 1,   p16↑, 1,   P53↓, 1,   P53↑, 7,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 3,   UHRF1↓, 2,   γH2AX↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 6,   CDK2↑, 1,   CDK4↓, 5,   CDK4↑, 1,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 6,   CycD3↓, 1,   cycE/CCNE↓, 3,   E2Fs↓, 1,   P21↑, 9,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   EMT↓, 2,   ERK↓, 2,   p‑ERK↓, 1,   FGF↓, 1,   FOXM1↓, 1,   FOXO↑, 2,   FOXO3↓, 1,   Gli1↓, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   HDAC1↓, 2,   HDAC2↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   HH↓, 1,   IGF-1↓, 1,   IGFBP3↓, 1,   mTOR↓, 6,   p‑mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   P70S6K↓, 1,   PI3K↓, 6,   PTEN↑, 2,   RAS↓, 1,   STAT1↓, 1,   STAT3↓, 6,   p‑STAT3↓, 1,   STAT4↓, 1,   STAT5↓, 1,   TumCG↓, 4,   Wnt↓, 4,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   ATPase↓, 1,   AXL↓, 1,   Ca+2↑, 1,   CAFs/TAFs↓, 1,   Cartilage↑, 1,   COL4↓, 1,   DLC1↑, 2,   E-cadherin↓, 1,   ITGA11↓, 1,   ITGA5↓, 1,   Ki-67↓, 3,   LAMB3↑, 1,   MMP2↓, 9,   MMP7↓, 3,   MMP9↓, 9,   MMP9↑, 1,   MMPs↓, 1,   N-cadherin↓, 1,   PDGF↓, 2,   Rho↑, 1,   ROCK1↑, 1,   Slug↓, 2,   Snail?, 1,   Snail↓, 1,   TGF-β↓, 3,   THBS2↓, 1,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 5,   TumMeta↓, 2,   TumMeta↑, 1,   Twist↓, 4,   uPA↓, 1,   Vim↓, 1,   Zeb1↓, 2,   ZEB2↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   EGFR↓, 1,   Hif1a↓, 7,   NO↓, 1,   VEGF↓, 8,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

CD4+↓, 1,   COX2↓, 7,   COX2↑, 2,   CRP↓, 1,   CXCL1↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IL1↓, 2,   IL1↑, 1,   IL10↓, 1,   IL10↑, 1,   IL12↓, 2,   IL17↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL2↑, 2,   IL22↓, 1,   IL23↓, 1,   IL28↓, 1,   IL4↓, 1,   IL4↑, 2,   IL5↓, 1,   IL6↓, 5,   IL8↓, 1,   JAK↓, 1,   JAK1↓, 1,   JAK2↓, 2,   M2 MC↓, 1,   NF-kB↓, 9,   p65↓, 3,   PGE2↓, 2,   PSA∅, 1,   TNF-α↓, 5,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 3,   ER(estro)↓, 2,   GR↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 5,   BioAv↑, 1,   ChemoSen↑, 5,   Dose↝, 1,   eff↓, 1,   eff↑, 11,   Half-Life↝, 1,   RadioS↑, 1,   selectivity↑, 6,   TET2↑, 2,  

Clinical Biomarkers ⓘ

BMD↑, 1,   BMPs↑, 1,   CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 1,   FOXM1↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 5,   Ki-67↓, 3,   Myc↓, 1,   PSA∅, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum⇅, 1,   hepatoP↑, 2,   OS↑, 2,   QoL↑, 1,  

Infection & Microbiome ⓘ

CD8+↓, 1,  
Total Targets: 268

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 12,   ARE↑, 1,   Bil↑, 2,   Catalase↑, 6,   Fenton↓, 2,   GCLC↑, 2,   GCLM↑, 2,   GPx↑, 4,   GSH↑, 7,   GSSG↓, 1,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 10,   Keap1↑, 1,   lipid-P↓, 8,   lipid-P↑, 1,   mt-lipid-P↓, 1,   MDA↓, 7,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 3,   NRF2↑, 12,   ROS↓, 19,   ROS↑, 1,   mt-ROS↓, 1,   SIRT3↑, 4,   SOD↑, 10,   SOD2↑, 2,   Trx↑, 1,   UCPs↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,   mitResp↑, 2,   MMP↑, 4,   PGC-1α↑, 4,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 4,   AMPK↑, 3,   CREB↓, 1,   CREB↑, 1,   G6PD↑, 1,   LDH↓, 2,   LDL↓, 1,   NADH:NAD↑, 1,   PPARγ↑, 21,   SIRT1↑, 6,  

Cell Death ⓘ

Akt↑, 1,   p‑Akt↑, 3,   Apoptosis↓, 2,   Bax:Bcl2↓, 1,   Casp3↓, 4,   Casp9↓, 1,   Casp9↑, 1,   Cyt‑c↓, 1,   Cyt‑c∅, 1,   iNOS↓, 3,   JNK↓, 1,   MAPK↓, 1,   p‑MAPK?, 1,   p‑MAPK↓, 1,   necrosis↓, 1,   p38↓, 1,   TRPV1↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 2,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   GRP78/BiP↓, 1,   GRP78/BiP↑, 1,   HSP27↑, 1,   HSP70/HSPA5↝, 1,   HSPs↓, 1,   UPR↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   ERK↑, 1,   p‑ERK↑, 1,   FOXO↑, 1,   GSK‐3β↓, 6,   PI3K↑, 1,  

Migration ⓘ

AntiAg↑, 2,   APP↓, 1,   Ca+2↓, 4,   Ca+2↑, 1,   CDK5↓, 1,   MMP9↓, 1,   Na+↑, 1,   Rho↓, 1,   VCAM-1↓, 2,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 5,   GLUT4↑, 1,   Na+↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   ICAM-1↓, 2,   IFN-γ↓, 1,   IL1↓, 1,   IL12↓, 1,   IL1β↓, 8,   IL33↓, 1,   IL4↑, 2,   IL6↓, 6,   IL8↓, 2,   Inflam↓, 17,   NF-kB↓, 13,   p65↓, 1,   PGE2↓, 4,   TLR4↓, 3,   TNF-α↓, 14,  

Synaptic & Neurotransmission ⓘ

5HT↑, 2,   AChE↓, 5,   AChE↑, 1,   BDNF↑, 7,   ChAT↑, 1,   GABA↑, 1,   MAOA↓, 1,   tau↓, 1,   p‑tau↓, 4,   TrkB↑, 2,  

Protein Aggregation ⓘ

Aβ↓, 13,   BACE↓, 2,   NLRP3↓, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↑, 5,   BioAv↝, 2,   Dose↝, 2,   eff↑, 6,   Half-Life↓, 1,   Half-Life↝, 2,   P450↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 4,   ALP↓, 1,   AST↓, 3,   Bil↑, 2,   BloodF↑, 1,   BP↓, 1,   GutMicro↑, 4,   IL6↓, 6,   LDH↓, 2,  

Functional Outcomes ⓘ

AntiCan↓, 1,   AntiCan↑, 1,   cardioP↑, 6,   chemoP↑, 1,   cognitive↑, 9,   hepatoP↑, 5,   memory↑, 8,   motorD↑, 5,   neuroP↑, 13,   radioP↑, 1,   RenoP↑, 1,   Risk↓, 1,   toxicity↓, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 152

Scientific Paper Hit Count for: PPARγ, Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG)
5 Honokiol
4 Thymoquinone
3 Curcumin
3 Lycopene
2 Ferulic acid
2 doxorubicin
2 Resveratrol
1 alpha Linolenic acid
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Baicalein
1 Berberine
1 Capsaicin
1 Carvacrol
1 Cannabidiol
1 Ginseng
1 Luteolin
1 Magnolol
1 Magnetic Field Rotating
1 Magnetic Fields
1 Oleuropein
1 HydroxyTyrosol
1 Piperine
1 Quercetin
1 Rosmarinic acid
1 Sesame seeds and Oil
1 Silymarin (Milk Thistle) silibinin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:259  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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