p38 Cancer Research Results

p38, p38: Click to Expand ⟱
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P38, or p38 MAPK (p38 mitogen-activated protein kinase), is a protein kinase that plays a significant role in cellular responses to stress, inflammation, and apoptosis (programmed cell death). It is part of the MAPK signaling pathway, which is involved in various cellular processes, including cell growth, differentiation, and survival.
It can have both tumor-suppressive and tumor-promoting effects, depending on the type of cancer and the cellular context.

-p38 activation can contribute to tumor progression by influencing inflammatory signaling and cell-cycle regulation.
-Overexpression can correlate with poor prognosis in some studies.
Scientific Papers found: Click to Expand⟱
2000- AL,    Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, NA
selectivity↑, The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells.
TumCG?,
*toxicity∅, no substantial cytotoxicity was seen in normal Vero cells
ROS↑, TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP
MMP↓,
TumCCA↑, increased the percentage of cells in the G2/M phase
P53↑, ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins.
Bcl-2↓,
p‑Akt↓,
p‑p38↓,
*ROS∅, Vero normal cells did not display the unusual morphological alteration and reduction in cell viability. ROS production revealed a 1.21 % ROS level only in control cells that is typically seen in healthy cells.

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↓,

1150- Api,    Apigenin inhibits the TNFα-induced expression of eNOS and MMP-9 via modulating Akt signalling through oestrogen receptor engagement
- in-vitro, Lung, EAhy926
eNOS↓, Apigenin (50 μM) counteracted the TNFα-induced expression of eNOS and MMP-9 and the TNFα- triggered activation of Akt, p38MAPK and JNK signalling
MMP9↓,
Akt↓,
p38↓,
JNK↓, Apigenin pre-treatment (50 lM) significantly inhibited the TNFa-induced phosphorylation of Akt (Fig. 2a), p38MAPK (Fig. 2b) and JNK

3392- ART/DHA,    Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways
- in-vitro, Nor, Hep3B - in-vivo, NA, NA
*Inflam↓, anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice.
*NF-kB↓, artemisinin significantly inhibited the expression of NF-?B reporter gene induced by TNF-? in a dose-dependent manner
*ROS↓, artemisinin significantly impaired the ROS production and phosphorylation of p38 and ERK,
*p‑p38↓,
*p‑ERK↓,

1148- ART/DHA,    Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages
- in-vitro, AML, THP1
MMP9↓,
EMMPRIN↓,
p‑PKCδ↓, artemisinin (20-80 μg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation
p‑JNK↓,
p‑p38↓,
p‑ERK↓,

573- ART/DHA,    Artesunate suppresses tumor growth and induces apoptosis through the modulation of multiple oncogenic cascades in a chronic myeloid leukemia xenograft mouse model
- vitro+vivo, NA, NA
p‑p38↓,
p‑ERK↓,
p‑CREB↓,
p‑Chk2↓,
p‑STAT5↓,
p‑RSK↓,
SOCS1↑,
Apoptosis↑,
Casp3↑,

5389- AsP,  Tras,    ASCORBYL PALMITATE ENHANCES ANTI-PROLIFERATIVE EFFECT OF TRASTUZUMAB IN HER2-POSITIVE BREAST CANCER CELLS
tumCV↓, AP reduced cell viability in a time- and dose-dependent manner, and its combination with trastuzumab further decreased cell viability.
eff↑, A cytometric analysis showed enhanced apoptosis after combination treatment
P53↑, mRNA analysis revealed upregulated TP53 mRNA expression, along with upregulation of BAX, CYCS, CASP3, and CASP8 gene expression, while the BCL-2 and BCL2L1 genes were downregulated, further supporting the induction of apoptosis.
BAX↑,
Casp3↑,
Casp8↑,
Bcl-2↓,
Apoptosis↑,
p‑p38↓, Western blot assay, which showed suppression of phospho-P38, ERK1/2, and PI3K protein synthesis.
ERK↓,
PI3K↓,

2480- Ba,    Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways
- in-vivo, Stroke, NA
*12LOX↓, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury
*ROS↓, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury
*ERK↑, mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts
*Akt↑,
*p38↓,
*JNK↓,
*NF-kB↓,
*cardioP↑, Baicalein inhibits cardiac injury and inflammation

2690- BBR,    Berberine Differentially Modulates the Activities of ERK, p38 MAPK, and JNK to Suppress Th17 and Th1 T Cell Differentiation in Type 1 Diabetic Mice
- in-vivo, Diabetic, NA
*Inflam↓, Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation.
*Th17↓, Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion.
*Th1 response↓,
*ERK↑, berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation.
*p38↓,
*JNK↓,
*STAT1↓, Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation,
*STAT4↓,
*MAPK↓,

3679- BBR,    Berberine alleviates Alzheimer's disease by activating autophagy and inhibiting ferroptosis through the JNK-p38MAPK signaling pathway
- in-vivo, AD, NA
*Beclin-1↑, autophagy-related markers Beclin1 and LC3B were upregulated and P62 was downregulated after BBR treatment.
*LC3B↑,
*p62↓,
*ROS↓, ROS and lipid peroxide MDA decreased significantly after BBR treatment.
*lipid-P↓,
*MDA↓,
*Ferroptosis↓, expression levels of ferroptosis-related genes TFR1, ASCL4, DMT1, and IREB2 were decreased, while the expression levels of FTH1 and SLC7A11 increased after BBR treatment.
*TfR1/CD71↓,
*FTH1↑,
*memory↑, BBR treatment enhanced spatial memory impairment in 5xFAD mice.
*JNK↓, inhibited ferroptosis by inhibiting the JNK-P38MAPK signaling pathway.
*p38↓,
*Aβ↓, further reducing Aβ plaque deposition, inhibiting inflammatory response,
*Inflam↓,

2758- BetA,    Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway
- in-vivo, Nor, NA
*ROS↓, protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied.
*MDA↓, BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus.
*SOD↑,
*GSH↑,
*p‑p38↓, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues.
*p‑JNK↓,
*p‑ERK↓,
*NRF2↑,
*HO-1↑,
*MAPK↓, suppressing the MAPK signaling pathway.
*heparanase↑, BA also showed protective activities against alcohol-induced liver damage and dexamethasone-induced spleen and thymus oxidative damage, and these protective effects were related to the antioxidant capacity of BA
*antiOx↑, BA Increased T-2 Toxin-Induced Thymus Antioxidative Capacity

2776- Bos,    Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities
- Review, Var, NA
*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)

5746- CA,    Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP
tumCV↓, CA inhibits prostate cancer cells (PC-3 and LNCaP) proliferation and induces reactive oxygen species (ROS), cell cycle arrest, and apoptosis cell death in a concentration-dependent manner.
ROS↑,
TumCCA↑, CA induces ROS production, G2/M cell cycle arrest and apoptotic cell death in prostate cancer cells
Apoptosis↑,
p‑MAPK↓, CA treatment alleviates the expression phosphorylated form of MAPK families, i.e., extracellular signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinase (JNK), and p38 in PC-3 cells.
ERK↓,
JNK↓,
p38↓,
IL6↓, CA inhibits the expression of IL-6, JAK1, and phosphorylated STAT-3 in both PC-3 and LNCaP cells.
JAK1↓,
p‑STAT3↓,
cycD1/CCND1↓, it resulted in decreased expression of cyclin-D1, cyclin-D2, and CDK1 in both PC-3 cells.
CDK1↓,
BAX↑, CA induces apoptosis by enhancing the expression of Bax and caspase-3; and decreased expression of Bcl-2 in prostate cancer cells.
Casp3↑,
Bcl-2↓,
TumCD↑, CA induces cell death and inhibits colony formation in prostate cancer cells

159- CUR,    Crosstalk from survival to necrotic death coexists in DU-145 cells by curcumin treatment
- in-vitro, Pca, DU145
ROS↑, at higher concentrations
p‑Jun↑, phosphorylation
p‑p38↑, Moreover, increased p38 phosphorylation was decreased soon after 4 h of curcumin treatment
TumAuto↑, curcumin-induced autophagy was related to caspase-dependent apoptotic cell death,
Casp8↑, Necrotic cell death by autophagy-induced caspase 8/9 degradation lasts until late stages of cell death after curcumin treatmen
Casp9↑,
Akt↓, decreased activities of Akt, ERK, and p38 after curcumin treatment (
ERK↓,
p38↓,

182- CUR,  RES,  GI,    Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
p38↓,
MKP5↑, MKP5 was up-regulated by curcumin and inhibited TNFa- and IL-1b-stimulated p38 phosphorylation, COX-2 up-regulation, NFjB activation and cytokine production in E-PZ cells
TNF-α↓,
COX2↓,
NF-kB↓,

691- EGCG,    Preclinical Pharmacological Activities of Epigallocatechin-3-gallate in Signaling Pathways: An Update on Cancer
- Review, NA, NA
Apoptosis↑,
necrosis↑,
TumAuto↑,
ERK↓, ERK1/2
p38↓,
NF-kB↓,
VEGF↓,

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

2850- FIS,    Fisetin regulates TPA-induced breast Cancer cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways
- in-vitro, BC, MCF-7
TumCI↓, Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways.
PKCδ↓,
ROS↓,
ERK↑,
p38↓,
NF-kB↓, reduced NF-κB activation
MMP9↓, reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression.

2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

2829- FIS,    Fisetin: An anticancer perspective
- Review, Var, NA
TumCP↓, Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage
TumCI↓,
TumCCA↑,
TumCG↓,
Apoptosis↑,
cl‑PARP↑,
PKCδ↓, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin
ROS↓,
ERK↓,
NF-kB↓,
survivin↓,
ROS↑, In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis
PI3K↓, Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)
Akt↓,
mTOR↓,
MAPK↓, phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively,
p38↓,
HER2/EBBR2↓, (HER2)/neu‐overexpressing breast cancer cell lines. Fisetin caused induction through inactivating the receptor, inducing the degradation of the proteasomes, reducing its half‐life
EMT↓, In addition, mutation of epithelial‐to‐mesenchymal transition (EMT)
PTEN↑, up‐regulation of expression of PTEN mRNA and protein were reported after fisetin treatment
HO-1↑, In breast cancer cells (4T1 and JC cells), fisetin increased HO‐1 mRNA and protein expressions, elevated Nrf2 expression
NRF2↑,
MMP2↓, fisetin reduced MMP‐2 and MMP‐9 enzyme activity and gene expression for both mRNA levels and protein
MMP9↓,
MMP↓, fisetin treatment further led to permeabilization of mitochondrial membrane, activation of caspase‐8 and caspase‐9, as well as the cleavage of poly(ADP‐ribose) polymerase 1
Casp8↑,
Casp9↑,
TRAILR↑, enhanced the levels of TRAIL‐R1
Cyt‑c↑, mitochondrial releasing of cytochrome c into cytosol, up‐regulation and down‐regulation of X‐linked inhibitor of apoptosis protein
XIAP↓,
P53↑, fisetin also enhanced the protein p53 levels
CDK2↓, lowered cell number, the activities of CDK‐2,4)
CDK4↓,
CDC25↓, it also decreased cell division cycle protein levels (CDC)2 and CDC25C, and CDC2 activity (Lu et al., 2005)
CDC2↓,
VEGF↓, down‐regulating the expressions of p‐ERK1/2, vascular endothelial growth factor receptor 1(VEGFR1), p38, and pJNK, respectively
DNAdam↑, Fisetin (80 microM) showed dose‐dependently caused DNA fragmentation, induced cellular swelling and apoptotic death, and showed characteristics of apoptosis.
TET1↓, lowered the TET1 expression levels
CHOP↑, caused up‐regulation of (C/EBP) homologous protein (CHOP) expression and reactive oxygen species production,
CD44↓, down‐regulation of CD44 and CD133 markers
CD133↓,
uPA↓, down‐regulation of levels of matrix metalloproteinase‐2 (MMP‐2), urokinase‐type plasminogen activator (uPA),
CSCs↓, Being a potent anticancer agent, fisetin administration in in vitro and in vivo studies in kidney renal stem cells (HuRCSCs) effectively inhibited cancer cell stages such as proliferation,

1117- Gb,    Ginkgobiloba leaf extract mitigates cisplatin-induced chronic renal interstitial fibrosis by inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells mediated by the Smad3/TGF-β1 and Smad3/p38 MAPK pathways
- vitro+vivo, Kidney, HK-2
α-SMA↓,
COL1↓,
TGF-β↓, TGF-β1
SMAD2↓,
SMAD3↓,
p‑SMAD2↓,
p‑SMAD3↓, EGb inhibited cisplatin-induced EMT of renal tubular epithelial cells by downregulating the smad3/TGF-β1 and smad3/p38 MAPK pathways and ultimately effectively ameliorated CRIF.
p38↓,
p‑p38↓,
Vim↓,
TIMP1↓,
CTGF↓,
E-cadherin↑,
MMP1:TIMP1↑,

1118- GSE,    Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF- β Signaling Pathway
- in-vitro, Bladder, T24/HTB-9 - in-vitro, Bladder, 5637
TumCMig↓,
TumCI↓,
MMP2↓,
MMP9↓,
EMT↓,
N-cadherin↓,
Vim↓,
Slug↓,
E-cadherin↑,
ZO-1↑,
p‑SMAD2↓,
p‑SMAD3↓,
p‑Akt↓,
p‑ERK↓,
p‑p38↓,

3774- H2,    The role of hydrogen in Alzheimer’s disease
- Review, AD, NA
*Inflam↓, hydrogen inhalation exhibit anti-inflammatory and anti-oxidant effects in many studies.
*antiOx↑,
*NLRP3↓, decline of nucleotide-binding domain leucin-rich repeat and pyrin domain-containing protein 3 (NLRP3) was proved to inhibit memory impairment and Aβ deposition.4
*memory↑,
*Aβ↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway
*SIRT1↑,
*FOXO3↑,
*p‑p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*JNK↓,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling and protecting mitochondria.
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels, estrogen receptor (ER) β
*ER(estro)↑,
*BDNF↑, and the expression of brain-derived neurotrophic factor (BDNF),

3766- H2,    The role of hydrogen in Alzheimer′s disease
- Review, AD, NA
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models
*Inflam↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway which could play a role in anti-oxidative stress,
*SIRT1↑,
*FOXO↑,
*mtDam↓, diminishing mitochondrial damage and acting as a neuroprotective agent, and neutralize ROS induced by Aβ
*neuroP↑,
*ROS↓,
*p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels
*BDNF↑, reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neuro-trophic factor (BDNF)
*memory↑, Li et al.71 found that hydrogen-rich saline could reduce learning and memory impairments and neural inflammation which were induced by Aβ in rats
*lipid-P↓, Moreover, hydrogen-rich saline suppressed lipid peroxidation products, inflammatory factor like interleukin-6 and TNF-α, and the activation of astrocytes
*IL6↓,
*TNF-α↓,
*JNK↓, protective effect of hydrogen-rich saline may be due to inhibition of the activation of JNK and NF-κB
*NF-kB↓,
*NLRP3↓, Hydrogen-rich water inhibit NLRP3, and weaken the oestrogen-ERβ-BDNF signalling pathway.

2911- LT,    Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes
- in-vitro, Nor, HaCaT
*MMP1↓, luteolin effectively suppressed PM-induced MMP-1 and COX-2 expression and reduced the production of the proinflammatory cytokine IL-6.
*COX2↓,
*IL6↓,
*AP-1↓, luteolin inhibited the activation of AP-1 and NF-κB pathways and decreased reactive oxygen species (ROS) levels in HaCaT cells.
*NF-kB↓,
*ROS↓,
*p‑MKK4↑, luteolin binds directly to mitogen-activated protein kinase kinase (MKK) 4, inhibiting its kinase activity . increases phosphorylation of MKK4
*p‑JNK↓, subsequently reducing the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase.
*p‑p38↓,

3267- Lyco,    Lycopene inhibits angiogenesis both in vitro and in vivo by inhibiting MMP-2/uPA system through VEGFR2-mediated PI3K-Akt and ERK/p38 signaling pathways
- in-vitro, Nor, HUVECs
*VEGF↓, highest dose used (400 μg/plug) completely inhibited the formation of vascular endothelial cells induced by vascular endothelial growth factor (VEGF).
*MMP2↓, lycopene inhibited tube formation, invasion, and migration in HUVECs, and such actions were accompanied by reduced activities of matrix metalloproteinase-2, urokinase-type plasminogen activator, and protein expression of Rac1
*uPA↓,
*Rac1↑,
*TIMP2↑, and by enhancing protein expression of tissue inhibitors of metalloproteinase-2 and plasminogen activator inhibitor-1.
*p38↓, lycopene attenuated VEGF receptor-2 (VEGFR2)-mediated phosphorylation of extracellular signal-regulated kinase (ERK), p38, and Akt as well as protein expression of PI3K.
*Akt↓,
*angioG↓, anti-angiogenic effect of lycopene both in vitro and in vivo.

3266- Lyco,    Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose
- in-vitro, Nor, NA
*p38↓, lycopene blocked phosphorylation of p38 MAPK in EPCs
*MAPK↓,

4777- Lyco,    Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells
- in-vitro, GC, AGS
*antiOx↑, Lycopene is a potent antioxidant carotenoid and is responsible for the red color of fruits and vegetables.
tumCV↓, Lycopene decreased cell viability and increased apoptotic indices (DNA fragmentation, apoptosis inducing factor, cleavage of caspase-3 and caspase-9, Bax/Bcl-2 ratio)
DNAdam↑,
Apoptosis↑,
cl‑Casp3↑,
cl‑Casp9↑,
Bax:Bcl2↑,
ROS↓, Lycopene reduced the level of intracellular and mitochondrial ROS
NF-kB↓, attenuation of the DNA-binding activity of NF-κB p50/p50 and the level of COX-2 gene expression.
COX2↓,
EGFR↓, Lycopene Reduces ROS Levels and Inhibits EGFR/Ras/ERK and p38 MAPK Signaling in AGS Cells
p38↓,

4527- MAG,    Magnolol inhibits growth and induces apoptosis in esophagus cancer KYSE-150 cell lines via the MAP kinase pathway
- in-vitro, ESCC, TE1 - in-vitro, ESCC, Eca109 - vitro+vivo, SCC, KYSE150
TumCP↓, We found that magnolol inhibits cellular proliferation of all three cell lines in a time- and dose-dependent manner
TumCMig↓, 20 µM magnolol markedly inhibited the migration ability of KYSE-150 cell which was accompanied with a decreased expression of MMP-2
MMP2↓,
Apoptosis↑, 100 µM magnolol significantly increased KYSE-150 cell apoptosis
cl‑Casp3↑, cleaved caspase-3, cleaved capsese-9 and Bax protein expression was increased and Bcl-2 protein expression was decreased after magnolol treatment.
cl‑Casp9↑,
BAX↑,
Bcl-2↓,
p‑p38↓, induced the phosphorylation of p38 and ERK1/2 in a concentration-dependent manner, suggesting the involvement of these kinases in the initiation of the apoptosis process.
TumCG↓, significantly suppressed KYSE-150 tumor cell growth in nude mouse xenograft models.

204- MFrot,  MF,    Rotating magnetic field improved cognitive and memory impairments in a sporadic ad model of mice by regulating microglial polarization
- in-vivo, AD, NA
*NF-kB↓, RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway.
*MAPK↓,
*TLR4↓,
*memory↑,
*cognitive↑,
*TGF-β1↑, RMF treatment promoted the expression of anti-inflammatory cytokines (TGF-β1, Arg-1, IL-4, IL-10)
*ARG↑, Arg-1
*IL4↑,
*IL10↑,
*IL6↓,
*IL1↓, IL-1β
*TNF-α↓,
*iNOS↓,
*ROS↓, in mice brain
*NO↓, in serum
*MyD88↓,
*p‑IKKα↓, phosphorylated IKKα/β, IкBα, NF-кB p65, JNK, p38,
*p‑IκB↓, IкBα
*p‑p65↓,
*p‑JNK↓,
*p‑p38↓,
*ERK↓,
*neuroP↑, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice.
*Aβ↓, RMF treatment reduced Aβ deposition in the AD model mice

1141- Myr,    Myricetin: targeting signaling networks in cancer and its implication in chemotherapy
- Review, NA, NA
*PI3K↑, apoptotic potential of myricetin is specific for affected cells. In healthy cells, it activates PI3K/Akt signaling and inhibits ERK/JNK pathway to induce cytoprotective influence
*Akt↑,
p‑Akt↓,
SIRT3↑,
p‑ERK↓,
p38↓,
VEGF↓,
MEK↓, MEK1
MKK4↓,
MMP9↓,
Raf↓,
F-actin↓,
MMP2↓,
COX2↓,
BMP2↓,
cycD1/CCND1↓,
Bax:Bcl2↑,
EMT↓,
EGFR↓,
TumAuto↑,

1807- NarG,    A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies
- Review, NA, NA
AntiTum↑, antitumor ability of naringin
TumCP↓,
tumCV↓,
TumCCA↑,
Mcl-1↓,
RAS↓,
e-Raf↓, suppressing the Ras/Raf/extracellular
VEGF↓,
AntiAg↑,
MMP2↓,
MMP9↓,
TIMP2↑,
TIMP1↑,
p38↓,
Wnt↓,
β-catenin/ZEB1↑,
Casp↑,
P53↑,
BAX↑,
COX2↓,
GLO-I↓,
CYP1A1↑,
lipid-P↓,
p‑Akt↓,
p‑mTOR↓,
VCAM-1↓,
P-gp↓,
survivin↓,
Bcl-2↓,
ROS↑, ↑oxidative stress, Prostate DU145 cell line 50–250 μM
ROS↑, ↑ROS, Stomach (Gastric) AGS cell line, 1–3 mM
MAPK↑,
STAT3↓,
chemoP↑, flavonoids have excellent radical scavenging and iron-chelating properties (Kaiserová et al., 2007), and they can act as an effective modulator for DOX-induced toxicity

1165- PI,    Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells
- in-vitro, GC, TMK-1
p38↓,
IL6↓,
STAT3↓,

61- QC,    Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, ARPE-19
p‑PI3K↓, combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-κB.
p‑Akt↓,
p‑ERK↓,
NF-kB↓,
p38↓,
ABCG2↓,
CD44↓, Quercetin alone exhibited significant cytotoxic effects on CD44+/CD133+
CD133↓,
CSCs↓,

3606- QC,    The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial
- Trial, Arthritis, NA
*motorD↑, Quercetin supplementation for 8 weeks significantly reduced EMS, morning pain, and after-activity pain
*Pain↓,
*TNF-α↓, Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo
*IL8↓, Other studies showed that 30 mM quercetin decreased gene expression and production of IL-8, 1L-6, IL-1b, and TNFa, which are the major inflammatory cytokines i
*IL6↓,
*IL1β↓,
*NF-kB↓, also inhibited the activity of NF-kB and P38-kinase protein
*p38↓,

3353- QC,    Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells
- in-vitro, Oral, KON - in-vitro, Nor, MRC-5
tumCV↓, reduced the vitality of KON cells and had minimal effect on MRC cells.
selectivity↑, Owing to the appropriate dosages of quercetin needed to treat these diseases, normal cells do not exhibit any overtly harmful side effects.
TumCCA↑, quercetin increased the percentage of dead cells and cell cycle arrests in the S and G2/M phases.
TumCMig↓, quercetin inhibited KON cells’ capacity for migration and invasion in addition to their effects on cell stability and structure
TumCI↓,
Apoptosis↑, inducing apoptosis and preventing metastasis, quercetin was found to downregulate the expression of BCL-2/BCL-XL while increasing the expression of BAX.
TumMeta↓,
Bcl-2↓,
BAX↑,
TIMP1↑, TIMP-1 expression was upregulated while MMP-2 and MMP-9 were downregulated.
MMP2↓,
MMP9↓,
*Inflam↓, anti-inflammatory, anti-cancer, antibacterial, antifungal, anti-diabetic, antimalarial, neuroprotective, and cardioprotective properties.
*neuroP↑,
*cardioP↑,
p38↓, MCF-7 cells, quercetin successfully decreased the expression of phosphor p38MAPK, Twist, p21, and Cyclin D1
MAPK↓,
Twist↓,
P21↓,
cycD1/CCND1↓,
Casp3↑, directly aided by the significant increase in caspase-3 and − 9 levels and activities
Casp9↑,
p‑Akt↓, High quercetin concentrations also caused an inhibition of Akt and ERK phosphorylation
p‑ERK↓,
CD44↓, reduced cell division and triggered apoptosis, albeit to a lesser degree in CD44+/CD24− cells.
CD24↓,
ChemoSen↑, combination of quercetin and doxorubicin caused G2/M arrest in T47D cells, and to a lesser amount in cancer stem cells (CSCs) that were isolate
MMP↓, (lower levels of ΔΨ m), which is followed by the release of Cyto C, AIF, and Endo G from mitochondria, which causes apoptosis and ultimately leads to cell death.
Cyt‑c↑,
AIF↑,
ROS↑, Compared to the control group, quercetin administration significantly raised ROS levels at 25, 50, 100, 200, and 400 µg/mL.
Ca+2↑, increased production of reactive oxygen species and Ca2+, decreased levels of mitochondrial membrane potential (ΔΨ m),
Hif1a↓, Quercetin treatment resulted in a considerable downregulation of HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels in HOS cells.
VEGF↓,

3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
TumCCA↓, inhibition of the cell cycle;
HSPs↓, inhibition of heat shock proteins;
RAS↓, inhibition of Ras protein expression.
ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
Ca+2↑,
MMP↓,
Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
Endon↑,
MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
MMP2↓,
MMP7↓,
MMP-10↓,
VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
NF-kB↓,
p65↓,
iNOS↓,
COX2↓,
uPA↓,
PI3K↓,
FAK↓,
MEK↓,
ERK↓,
JNK↓,
p38↓,
cJun↓,
FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a

156- Ralox,  Tam,  GEN,  CUR,    Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ERβ/ESR2↑,
TumCG↓, Regulation of PC cell growth by raloxifen, tamoxifen, genistein and curcumin
TumCMig↓, genistein and curcumin reduced the migratory activity of DU145 cells by 43% and 25%, respectively; for PC3 cells the reduction was about 40%
FAK↓, genistein seemed to be an inhibition of the activation of Focal Adhesion Kinase (FAK) and mitogen-activated kinase (MAPK) p38-heat shock protein 27 that mediates detachment and cellular migration respectively
p38↓,

3001- RosA,    Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
- Review, Var, NA
TumCP↓, including in tumor cell proliferation, apoptosis, metastasis, and inflammation
Apoptosis↑,
TumMeta↓,
Inflam↓,
*antiOx↑, RA is therefore considered to be the strongest antioxidant of all hydroxycinnamic acid derivatives
*AntiAge↑, , it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects
*ROS↓, RA and its metabolites can directly neutralize reactive oxygen species (ROS) [10] and thereby reduce the formation of oxidative damage products.
BioAv↑, RA is water-soluble, and according to literature data, the efficacy of secretion of this compound in infusions is about 90%
Dose↝, Accordingly, it is possible to consume approximately 110 mg RA daily, i.e., approximately 1.6 mg/kg for adult men weighing 70 kg.
NRF2↑, liver cancer cell line, HepG2, transfected with plasmid containing ARE-luciferin gene, RA predominantly enhances ARE-luciferin activity and promotes nuclear factor E2-related factor-2 (Nrf2) translocation from cytoplasm to the nucleus
P-gp↑, and also increases MRP2 and P-gp efflux activity along with intercellular ATP level
ATP↑,
MMPs↓, RA concurrently induced necrosis and apoptosis and stimulated MMP dysfunction activated PARP-cleavage and caspase-independent apoptosis.
cl‑PARP↓,
Hif1a↓, inhibits transcription factor hypoxia-inducible factor-1α (HIF-1α) expression
GlucoseCon↓, it also suppressed glucose consumption and lactate production in colorectal cells
lactateProd↓,
Warburg↓, may suppress the Warburg effects through an inflammatory pathway involving activator of transcription-3 (STAT3) and signal transducer of interleukin (IL)-6
TNF-α↓, RA supplementation also reduced tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and IL-6 levels, and modulated p65 expression [
COX2↓,
IL6↓,
HDAC2↓, RA induced the cell cycle arrest and apoptosis in prostate cancer cell lines (PCa, PC-3, and DU145) [31]. These effects were mediated through modulation of histone deacetylases expression (HDACs), specifically HDAC2;
GSH↑, RA can also inhibit adhesion, invasion, and migration of Ls 174-T human colon carcinoma cells through enhancing GSH levels and decreasing ROS levels
ROS↓,
ChemoSen↑, RA also enhances chemosensitivity of human resistant gastric carcinoma SGC7901 cells
*BG↓, RA significantly increased insulin index sensitivity and reduced blood glucose, advanced glycation end-products, HbA1c, IL-1β, TNFα, IL-6, p-JNK, P38 mitogen-activated protein kinase (MAPK), and NF-κB levels
*IL1β↓,
*TNF-α↓,
*IL6↓,
*p‑JNK↓,
*p38↓,
*Catalase↑, The reduced activities of CAT, SOD, glutathione S-transferases (GST), and glutathione peroxidase (GPx) and the reduced levels of vitamins C and E, ceruloplasmin, and GSH in plasma of diabetic rats were also significantly recovered by RA application
*SOD↑,
*GSTs↑,
*VitC↑,
*VitE↑,
*GSH↑,
*GutMicro↑, protective effects of RA (30 mg/kg) against hypoglycemia, hyperlipidemia, oxidative stress, and an imbalanced gut microbiota architecture was studied in diabetic rats.
*cardioP↑, Cardioprotective Activity: RA also reduced fasting serum levels of vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), plasminogen-activator-inhibitor-1 (PAI-1), and increased GPX and SOD levels
*ROS↓, Finally, in H9c2 cardiac muscle cells, RA inhibited apoptosis by decreasing intracellular ROS generation and recovering mitochondria membrane potential
*MMP↓,
*lipid-P↓, At once, RA suppresses lipid peroxidation (LPO) and ROS generation, whereas in HSC-T6 cells it increases cellular GSH.
*NRF2↑, Additionally, it significantly increases Nrf2 translocation
*hepatoP↑, Hepatoprotective Activity
*neuroP↑, Nephroprotective Activity
*P450↑, RA also reduced CP-produced oxidative stress and amplified cytochrome P450 2E1 (CYP2E1), HO-1, and renal-4-hydroxynonenal expression.
*HO-1↑,
*AntiAge↑, Anti-Aging Activity
*motorD↓, A significantly delays motor neuron dysfunction in paw grip endurance tests,

1209- SANG,    Sanguinarine is a novel VEGF inhibitor involved in the suppression of angiogenesis and cell migration
- in-vitro, Lung, A549
VEGF↓,
TumCMig↓,
Akt↓,
p38↓,

1457- SFN,    Sulforaphane Inhibits IL-1β-Induced IL-6 by Suppressing ROS Production, AP-1, and STAT3 in Colorectal Cancer HT-29 Cells
- in-vitro, CRC, HT-29
IL6↓, Sulforaphane inhibits the expression of IL-6 in HT-29 cells by inhibiting the production of ROS
ROS↓, reduces oxidative stress by curtailing reactive oxygen species (ROS) production.
TumCP↓,
TumCI↓,
p38↓,
AP-1↓,

1452- SFN,    Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells
- in-vitro, GC, AGS
MMP9↓, Sulforaphane effectively suppressed ROS, p38 MAPK, Erk1/2, AP-1, and NF-κB activation by inhibiting MMP-9 expression in gastric cancer AGS cells.
p38↓,
ERK↓,
AP-1↓,
ROS↓, results indicate that sulforaphane suppressed the nicotine-induced MMP-9 via regulating ROS generation in human gastric cancer AGS cells ( by Inhibiting ROS Generation)
NF-kB↓, Sulforaphane Suppresses Nicotine-Induced MMP-9 Expression by Inhibiting Reporter Activities of AP-1 and NF-κB
TumCI↓,
MMP9↓, Suppressing MMP-9 Expression
HDAC↓, Rutz et al. reported that sulforaphane acts as a histone deacetylase (HDAC) inhibitor to prostate cancer cell progression
Glycolysis↓, sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by inhibiting hypoxia-induced HIF-1α
Hif1a↓,
*memory↑, Sulforaphane could prevent memory dysfunction and improve cognitive function
*cognitive↑,

3331- SIL,    The clinical anti-inflammatory effects and underlying mechanisms of silymarin
- Review, NA, NA
*Inflam↓, anti-inflammatory mechanisms of silymarin,
*NF-kB↓, inhibition of the NF-kB and NLRP3 signaling pathways and the suppression of COX-2 and inducible nitric oxide synthase (iNOS) expression
*NLRP3↓,
*COX2↓,
*iNOS↓,
*neuroP↑, silymarin offers neuroprotection by inhibiting the phosphorylation of ERK1/2, JNK, and p38 MAPK and reducing the expression of the epidermal growth factor receptor and glial fibrillary acidic protein
*p‑ERK↓,
*p38↓,
*MAPK↓,
*EGFR↓,
*ROS↓, By the way, silymarin was reported to curb the formation of oxygen radicals and lipid peroxides.
*lipid-P?,
*5LO↓, Its anti-inflammatory effects were shown by inhibiting 5-LOX activity and obstructing the lipid peroxidation pathway to prevent the generation of ROS involved in inflammatory responses.

3319- SIL,    Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, Silymarin can be used as a neuroprotective therapy against AD, PD and CI
*ROS↓, Silymarin prohibit oxidative stress, pathologic protein aggregation.
*Inflam↓, Silymarin inhibit neuroinflammation, apoptosis, and estrogenic receptor modulation.
*Apoptosis↓,
*BBB?, Silymarin, as a polyphenolic complex, can cross the blood-brain barrier (BBB)
*tau↓, inhibitory action of Silibinin on tau protein phosphorylation in the hippocampus and cortical region of the brain could describe an important neuro-protective effect against AD progression
*NF-kB↓, inhibiting the NF-κB pathway leading to attenuating the activity of NF-κB (
*IL1β↓, inhibition of inflammatory responses such as IL-1β and TNF-α mRNA gene
*TNF-α↓,
*IL4↓, enhance the production of IL-4 in the hippocampal region
*MAPK↓, down-regulation of MAPK activation
*memory↑, Silibinin exhibited its beneficial effect on improvement of memory impairment in rats
*cognitive↑, Silymarin was able to alleviated the impairment in cognitive, learning and memory ability caused by Aβ aggravation through making a reduction in oxidative stress in the hippocampal region
*Aβ↓,
*ROS↓,
*lipid-P↓, eduction in lipid peroxidation, controlling the GSH levels and then cellular anti-oxidant status improvement,
*GSH↑,
*MDA↓, Silymarin could reduce MDA content and significantly increased the reduced activity level of antioxidant enzyme, including SOD, CAT and GSH in the brain tissue induced by aluminum
*SOD↑,
*Catalase↑,
*AChE↓, Silibinin/ Silymarin, as a strong suppressor of AChE and BChE activity, exerted a positive effect against AD symptoms via increasing the ACh level in the brain
*BChE↓,
*p‑ERK↓, Silibinin could inhibit increased level of phosphorylated ERK, JNK and p38 (p-ERK, p-JNK and p-p38, respectively
*p‑JNK↓,
*p‑p38↓,
*GutMicro↑, demonstrated in APP/PS1 transgenic mice model of AD which was associated with controlling of the gut microbiota by both Silymarin and Silibinin
*COX2↓, Inhibition of the NF-κB pathway/ expression, Inhibition of IL-1β, TNF-α, COX_2 and iNOS level/ expression
*iNOS↓,
*TLR4↓, suppress TLR4 pathways and then subsequently diminished elevated level of TNF-α and up-regulated percentage of NF-κB mRNA expression
*neuroP↑, neuro-protective mechanisms on cerebral ischemia (CI)
*Strength↑, Silymarin decreased the loss of grip strength in the experimental rats
*AMPK↑, In SH-SY5Y cells, Silibinin blocked OGD/re-oxygenation- induced neuronal degeneration via AMPK activation as well as suppression in both ROS production and MMP reduction and even reduced neuronal apoptosis and necrosis.
*MMP↑,
*necrosis↓,
*NRF2↑, Silymarin up-regulated Nrf-2/HO-1 signaling (Yuan et al., 2017
*HO-1↑,

3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, graphical abstract
TumCCA↑,
Apoptosis↓,
TumMeta↓,
TumCG↓,
angioG↓,
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,
p‑ERK↓, fig 2
p‑p38↓,
p‑JNK↓,
P53↑,
Bcl-2↓,
Bcl-xL↓,
TGF-β↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
Wnt↓,
Vim↓,
VEGF↓,
IL6↓,
STAT3↓,
*ROS↓,
IL1β↓,
PGE2↓,
CDK1↓, Causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9,
CycB/CCNB1↓,
survivin↓,
Mcl-1↓,
Casp3↑,
Casp9↑,
cMyc↓, Silibinin treatment diminishes c-MYC
COX2↓, Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, Ang-4, MMP-2, MMP-9, CCR-2 and CXCR-4
Hif1a↓,
CXCR4↓,
CSCs↓, HCT-116 cells, Induction of apoptosis, suppression of migration, elimination of CSCs. Attenuation of EMT via decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin).
EMT↓,
N-cadherin↓,
PCNA↓, Decrease in PCNA and cyclin D1 level.
cycD1/CCND1↓,
ROS↑, Hepatocellular carcinoma: Silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation.
eff↑, Silymarin + Curcumin
eff↑, Silibinin + Metformin
eff↑, Silibinin + 1, 25-vitamin D3
HER2/EBBR2↓, Significant down regulation of HER2 by 150 and 250 µM of silybin after 24, 48 and 72 h.

3305- SIL,    Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, NA, NA
TumCP↓, Silymarin decreased the viability and proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner.
tumCV↓,
BAX↑, Silymarin increased the levels of Bax, cleaved poly-ADP ribose polymerase, cleaved caspase-9 and phosphorylated (p-)JNK, and decreased the levels of Bcl-2, p-P38 and p-ERK1/2.
cl‑PARP↑,
Casp9↑,
p‑JNK↑,
Bcl-2↓,
p‑p38↓,
p‑ERK↓,
*toxicity∅, In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF-7 tumor growth was inhibited without organ toxicity
Dose↝, cell viability increased to 110% @ low dose 25ug/ml before dropping see figure 1
*hepatoP↑, silymarin is used as a healthy functional food in recognition of the hepatoprotective effects and has been reported the various effects such as inflammation (750 mg/kg/day), antioxidants (150 mg/kg−1) and anti-cancer
Inflam↓,
AntiCan↑,

2211- SK,    Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways
- in-vivo, ostP, NA
*BMD↑, Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo.
*p‑NF-kB↓, shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38.
*p‑p50↓, by inhibiting phosphorylation of P65, P50, and IkB protein.
*p‑p65↓,
*p‑ERK↓, shikonin blocked the MAPK pathway via preventing phosphorylation of ERK, JNK, and P38
*p‑cJun↓,
*p‑p38↓,

2231- SK,    Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways
- in-vitro, CRC, SNU-407
Apoptosis↑, Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members
ER Stress↑, apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress
PERK↑, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca2+ accumulation.
eIF2α↑,
CHOP↑,
mt-Ca+2↑,
MMP↓, Shikonin increased mitochondrial membrane depolarization
Bcl-2↓, decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3.
Casp3↑,
Casp9↑,
ERK↑, Shikonin treatment activated ERK, JNK, and p38 MAPK in a time-dependent manner
JNK↑,
p38↓,

3042- SK,    The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathways
- in-vivo, Nor, NA
*TNF-α↓, Our results showed that SHK treatment distinctly decreased serum TNF-a, IL-1b, IL-6 and IFN-g inflammatory cytokine production
*IL1β↓,
*IL6↓,
*IFN-γ↓,
*ALAT↓, , reduced serum ALT, AST, hepatic MPO and ROS production levels,
*AST↓,
*MPO↓,
*ROS↓,
*JNK↓, inhibited JNK1/2, ERK1/2, p38 and NF-kB (p65) phosphorylation, and suppressed IkBa phosphorylation and degradation.
*ERK↓,
*p38↓,
*NF-kB↓,
*p‑IKKα↓,
*SOD↑, SHK could dramatically increase SOD and GSH production, as well as reduce ROS production,
*GSH↑,
*HO-1↑, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation.
*NRF2↑,
*hepatoP↑,


Showing Research Papers: 1 to 50 of 54
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 54

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

CYP1A1↑, 1,   GSH↑, 1,   GSTs↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   lipid-P↑, 1,   NRF2↓, 1,   NRF2↑, 3,   ROS↓, 7,   ROS↑, 11,   ROS⇅, 1,   mt-ROS↑, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   ATP↑, 1,   CDC2↓, 2,   CDC25↓, 3,   EGF↓, 1,   MEK↓, 2,   MKK4↓, 1,   MKP5↑, 1,   MMP↓, 8,   MPT↑, 1,   Raf↓, 1,   e-Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↓, 1,   AMPK↑, 1,   cMyc↓, 1,   p‑CREB↓, 1,   FASN↓, 1,   GLO-I↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PCK1↓, 1,   PPARγ↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 6,   p‑Akt↓, 7,   Apoptosis↓, 1,   Apoptosis↑, 10,   BAD↑, 1,   BAX↑, 8,   Bax:Bcl2↑, 2,   Bcl-2↓, 12,   Bcl-xL↓, 1,   BIM↑, 1,   BMP2↓, 1,   Casp↑, 3,   Casp3↑, 9,   cl‑Casp3↑, 2,   Casp8↑, 4,   Casp9↑, 6,   cl‑Casp9↑, 2,   Chk2↑, 1,   p‑Chk2↓, 1,   Cyt‑c↑, 7,   Diablo↑, 3,   DR5↑, 2,   Endon↑, 1,   Fas↑, 1,   IAP2↓, 1,   ICAD↓, 1,   iNOS↓, 2,   JNK↓, 3,   JNK↑, 1,   p‑JNK↓, 2,   p‑JNK↑, 1,   MAPK↓, 3,   MAPK↑, 1,   p‑MAPK↓, 1,   Mcl-1↓, 3,   Myc↓, 1,   necrosis↑, 1,   p38↓, 22,   p‑p38↓, 10,   p‑p38↑, 1,   p‑RSK↓, 1,   survivin↓, 5,   TRAILR↑, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 2,   SOX9↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,   p‑H3↓, 1,   tumCV↓, 6,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   eIF2α↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 1,   HSPs↓, 1,   PERK↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3s↑, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

ATM↑, 1,   CHK1↑, 1,   DNAdam↑, 4,   P53↑, 7,   cl‑PARP↓, 1,   cl‑PARP↑, 5,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   p‑CDK1↓, 1,   CDK2↓, 3,   CDK4↓, 3,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 7,   P21↓, 1,   P21↑, 2,   p‑RB1↓, 1,   TumCCA↓, 1,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 2,   CD24↓, 1,   CD44↓, 3,   cFos↓, 1,   CSCs↓, 4,   EMT↓, 5,   ERK↓, 7,   ERK↑, 2,   p‑ERK↓, 10,   FOXM1↓, 1,   FOXO3↑, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   HDAC↓, 1,   HDAC2↓, 1,   p‑Jun↑, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   mTORC1↓, 1,   mTORC2↓, 1,   PI3K↓, 4,   p‑PI3K↓, 1,   PTEN↑, 1,   RAS↓, 3,   STAT3↓, 5,   p‑STAT3↓, 1,   p‑STAT5↓, 1,   TOP2↓, 1,   TumCG?, 1,   TumCG↓, 4,   Wnt↓, 3,  

Migration ⓘ

AntiAg↑, 1,   AP-1↓, 2,   Ca+2↑, 3,   mt-Ca+2↑, 1,   cal2↓, 1,   COL1↓, 1,   CTGF↓, 1,   E-cadherin↑, 5,   EMMPRIN↓, 1,   F-actin↓, 1,   FAK↓, 2,   Fibronectin↓, 1,   Ki-67↓, 1,   MET↓, 1,   MMP-10↓, 1,   MMP1↓, 1,   MMP1:TIMP1↑, 1,   MMP13↓, 1,   MMP2↓, 10,   MMP3↓, 1,   MMP7↓, 3,   MMP9↓, 15,   MMPs↓, 2,   N-cadherin↓, 3,   PKCδ↓, 2,   p‑PKCδ↓, 1,   Rho↓, 1,   ROCK1↑, 1,   Slug↓, 1,   SMAD2↓, 1,   p‑SMAD2↓, 2,   SMAD3↓, 1,   p‑SMAD3↓, 2,   Snail↓, 1,   TET1↓, 1,   TGF-β↓, 2,   TIMP1↓, 1,   TIMP1↑, 2,   TIMP2↑, 1,   TumCI↓, 6,   TumCMig↓, 5,   TumCP↓, 6,   TumMeta↓, 4,   Twist↓, 3,   uPA↓, 4,   VCAM-1↓, 1,   Vim↓, 4,   Zeb1↓, 1,   ZO-1↑, 1,   α-SMA↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   ATF4↓, 1,   EGFR↓, 3,   eNOS↓, 2,   Hif1a↓, 5,   NO↓, 1,   VEGF↓, 12,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,   P-gp↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 9,   CRP↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IL1β↓, 2,   IL6↓, 6,   Inflam↓, 3,   JAK1↓, 2,   NF-kB↓, 10,   p65↓, 2,   PGE2↓, 1,   SOCS1↑, 1,   TNF-α↓, 4,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   ERβ/ESR2↑, 1,  

Drug Metabolism & Resistance ⓘ

ABCG2↓, 1,   BioAv↑, 1,   ChemoSen↑, 4,   Dose↝, 3,   eff↑, 5,   Half-Life↓, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 3,   FOXM1↓, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 2,   IL6↓, 6,   Ki-67↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   chemoP↑, 3,   hepatoP↑, 1,   neuroP↑, 1,   radioP↑, 1,   RenoP↑, 1,  
Total Targets: 251

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 8,   ARE↑, 1,   Bil↑, 1,   Catalase↑, 4,   Fenton↓, 1,   Ferroptosis↓, 1,   GCLC↑, 1,   GCLM↑, 1,   GSH↑, 4,   GSTs↑, 1,   HO-1↑, 5,   lipid-P?, 1,   lipid-P↓, 6,   MDA↓, 4,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 6,   ROS↓, 16,   ROS∅, 1,   SOD↑, 6,   VitC↑, 1,   VitE↑, 1,  

Metal & Cofactor Biology ⓘ

FTH1↑, 1,   IronCh↑, 1,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

p‑MKK4↑, 1,   MMP↓, 1,   MMP↑, 1,   mtDam↓, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,   ALAT↓, 1,   AMPK↑, 3,   PPARγ↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 2,   Apoptosis↓, 1,   Ferroptosis↓, 1,   iNOS↓, 5,   JNK↓, 7,   p‑JNK↓, 6,   MAPK↓, 6,   p‑MAPK↓, 1,   necrosis↓, 1,   p38↓, 12,   p‑p38↓, 7,  

Transcription & Epigenetics ⓘ

p‑cJun↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B↑, 1,   p62↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 2,   ERK↑, 2,   p‑ERK↓, 5,   FOXO↑, 1,   FOXO3↑, 1,   PI3K↑, 1,   STAT1↓, 1,   STAT4↓, 1,  

Migration ⓘ

5LO↓, 2,   AP-1↓, 1,   ARG↑, 1,   Ca+2↓, 1,   heparanase↑, 1,   MMP1↓, 1,   MMP2↓, 1,   MMP3↓, 1,   Rac1↑, 1,   TGF-β1↑, 1,   TIMP2↑, 1,   uPA↓, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   NO↓, 2,   NO↑, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB?, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 5,   ICAM-1↓, 1,   IFN-γ↓, 1,   p‑IKKα↓, 2,   IL1↓, 1,   IL10↑, 1,   IL1β↓, 6,   IL4↓, 1,   IL4↑, 1,   IL6↓, 8,   IL8↓, 2,   Inflam↓, 10,   p‑IκB↓, 1,   MyD88↓, 1,   NF-kB↓, 10,   p‑NF-kB↓, 1,   p‑p50↓, 1,   p‑p65↓, 2,   PGE2↓, 2,   PGE2↑, 1,   Th1 response↓, 2,   Th17↓, 1,   Th2↑, 2,   TLR4↓, 2,   TNF-α↓, 8,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,   BDNF↑, 3,   ChAT↑, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 5,   NLRP3↓, 4,  

Hormonal & Nuclear Receptors ⓘ

ER(estro)↑, 1,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,   Half-Life↝, 1,   P450↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BG↓, 1,   Bil↑, 1,   BMD↑, 1,   EGFR↓, 1,   GutMicro↑, 3,   IL6↓, 8,  

Functional Outcomes ⓘ

AntiAge↑, 2,   cardioP↑, 3,   cognitive↑, 6,   hepatoP↑, 4,   memory↑, 7,   motorD↓, 1,   motorD↑, 1,   neuroP↑, 9,   Pain↓, 1,   radioP↑, 1,   RenoP↑, 1,   Strength↑, 1,   toxicity↓, 1,   toxicity∅, 2,  
Total Targets: 136

Scientific Paper Hit Count for: p38, p38
5 Fisetin
4 Quercetin
4 Silymarin (Milk Thistle) silibinin
3 Artemisinin
3 Curcumin
3 Lycopene
3 Shikonin
2 Berberine
2 Hydrogen Gas
2 Sulforaphane (mainly Broccoli)
2 Thymoquinone
1 Allicin (mainly Garlic)
1 alpha Linolenic acid
1 Apigenin (mainly Parsley)
1 Ascorbyl Palmitate
1 Trastuzumab
1 Baicalein
1 Betulinic acid
1 Boswellia (frankincense)
1 Caffeic acid
1 Resveratrol
1 Ginger/6-Shogaol/Gingerol
1 EGCG (Epigallocatechin Gallate)
1 Ferulic acid
1 Ginkgo biloba
1 Grapeseed extract
1 Luteolin
1 Magnolol
1 Magnetic Field Rotating
1 Magnetic Fields
1 Myricetin
1 Naringin
1 Piperine
1 Kaempferol
1 raloxifen
1 tamoxifen
1 Genistein (soy isoflavone)
1 Rosmarinic acid
1 Sanguinarine
1 5-fluorouracil
1 Vitamin C (Ascorbic Acid)
1 Vitamin K2
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#:235  State#:%  Dir#:1
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