p38 Cancer Research Results

p38, p38: Click to Expand ⟱

Source:

Type:

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

5–20 mg/mL

13.69 mg/mL

in-vitro,

BC,

MCF7

5–20 mg/mL5–20 mg/mL

15.35 mg/mL

in-vitro,

Nor,

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,

PPARγ↑,
COX2/PTGS2↓,
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

50 μM

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,

TPA-induced skin inflammation in mice.

*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

20-80 μg/mL

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,

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,

rat

*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,

berberine (Sigma, 200 mg/kg body weight), by gavage, daily for 2 weeks

11-week-old female NOD mice

*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,

5xFAD mice

*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↓,

6503-

BCP,

The Potential Therapeutic Role of Beta-Caryophyllene as a Chemosensitizer and an Inhibitor of Angiogenesis in Cancer

Review,

Var,

ChemoSen↑, Beta-Caryophyllene (BCP), was highlighted in several recent preclinical studies to enhance chemo-sensitization in chemo-resistant tumors and to efficiently inhibit angiogenesis and cancer cells’ ability to invade and metastasize.
angioG↓,
TumCI↓,
TumMeta↓,
ROS↑, BCP seems to work as a dual modulator of oxidative stress, increasing reactive oxygen species (ROS) in cancer cells, and thus enhancing apoptosis, but reducing ROS in normal cells to protect them from damage
*ROS↓,
chemoP↑,
CB2 / CNR2↑, important issue in BCP is its ability to bind to the body’s cannabinoid receptor 2 (CB2), where it binds selectively to the CB2 receptors and not the CB1 receptor, which makes it non-psychoactive and therapeutically appealing.
Inflam↓, activation of the CB2 receptor by BCP can suppress pro-inflammatory cytokines production, helping to create an anti-tumor immune environment
AntiTum↑,
*BioAv↑, Beta-Caryophyllene, a food additive approved by the Food and Drug Administration, is efficiently absorbed in the gastro-intestinal tract and can penetrate the blood–brain barrier and has a well-established safety profile, making it an attractive biom
*BBB↑,
Apoptosis↑, Induces apoptosis and suppresses proliferative activity of lung cancer cells
TumCP↑,
TumCCA↑, Induces G1 cell cycle arrest by dysregulating cyclins and other molecules
RadioS↑, GBM: Works as a potential radiosensitizer for improving RT outcomes by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways
DNArepair↓,
ROS↑, BC: Enhances sensitization and promotes the cigarette smoke condensate (CSC)-induced apoptosis in MDA-MB-468 cells, mainly by triggering oxidative stress and inhibition of STAT3
STAT3↓,
*BioEnh↑, BCP is considered a key component in black pepper’s ability to enhance nutrient absorption, including compounds like curcumin.
Pain↓, BCP in cloves further supports their role in pain management and infection prevention.
AntiBio↓,
ROS↑, selectively induce apoptosis and oxidative stress in cancer cells while sparing normal cells at lower concentrations.
Dose↝, I50, for many cancer cell lines typically ranges from 19 to 64 μM
NF-kB↓, Beta-Caryophyllene was reported to inhibit the central to the regulators of inflammation, NF-κB and MAPK pathways, leading to a decrease in pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) production
MAPK↓,
TNF-α↓,
IL1β↓,
IL6↓,
cl‑PARP↑, through increasing the levels of cleaved PARP, caspases and Bax, and the downregulation of Bcl-2, directly by interaction with CB2.
Casp↑,
BAX↑,
Bcl-2↓,
VEGF↓, BCP blocks migration of endothelial cells by inhibiting the secretion of VEGF, and thus blocking the activity of the tyrosine kinase VEGFR2
VEGFR2/KDR/Flk1↓,
MMP2↓, BCP can also prohibit the secretion of MMP-2, p-p38 and p-ERK
p‑p38↓,
p‑ERK↓,
EPR↑, BCP was suggested to accumulate in the cancer cell membrane, altering the cells’ permeability, leading to the accumulation of anticancer drugs, and consequently strengthening the drugs’ activity.
P-gp/ABCB1↓, direct inhibition of P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1), which are overexpressed in resistant tumors
MRP1/ABCC1↓,
*NRF2↑, Importantly, BCP’s selective antioxidant activity—activating Nrf2 in normal cells while increasing ROS in cancer cells—minimizes off-target toxicity,
*antiOx↑,

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,

mice

*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,

*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2/PTGS2↓, 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/DDIT3↑,
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)

6553-

BSB,

Pharmacological and biological effects of alpha-bisabolol: An updated review of the molecular mechanisms

Review,

Nor,

*ROS↓, Various therapeutic and biological properties of α-bisabolol in preventing oxidative stress, inflammatory disorders, infections, neurodegenerative diseases, cancers, and metabolic disorders have been reported.
*Inflam↓,
*Inf↓,
*neuroP↑,
*RNS↓, The antioxidant mechanism of α-bisabolol is mainly associated with the reduction of ROS/RNS, MDA, and GSH depletion, MPO activity, and augmentation of SOD and CAT.
*MDA↓,
*GSH↑,
*MPO↓,
*SOD↑,
*Catalase↑,
*Bcl-2↑, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3, and caspase-9 activity indicates the anti-apoptotic effects of α- bisabolol.
*BAX↓,
*P53↓,
*APAF1↓,
*Casp3↓,
*Casp9↓,
*TNF-α↓, It possesses anti-inflammatory effects via reduction of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and suppresses the activation of ERK1/2, JNK, NF-κB, and p38.
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2/PTGS2↓,
*ERK↓,
*JNK↓,
*NF-kB↓,
*p38↓,
*cognitive↑, improves cognitive function via downregulation of bax, cleaved caspases-3 and 9 levels, β-secretase, cholinesterase activities, and upregulation of bcl-2 levels.
*BChE↓,

7521-

CA,

Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells

in-vitro,

AD,

HT22

 HT22 mouse hippocampal cells

*neuroP↑, CA/CAPE significantly attenuated acrolein-induced neurotoxicity, ROS accumulation, and GSH depletion.
*ROS↓,
*GSH↑,
*Akt↑, CA/CAPE showed protective effects against acrolein by modulating MAPKs and Akt/GSK3β signaling pathways.
*GSK‐3β↑,
*BACE/β-secretase↓, CA/CAPE restored the changes of β-secretase (BACE-1) and/or activation of α-secretase (ADAM-10) induced by acrolein.
*p38↓, CA/CAPE inhibited the activation of p38 and JNK1 while promoted the activation of ERK and Akt/GSK3 caused by acrolein
*RAGE↓, In our study, ADAM-10 and LR-11 were decreased while BACE-1 and RAGE were increased after the exposure of acrolein for 24 h (Fig. 3). Of interest, these changes were almost restored by both CA and CAPE
*ADAM10↑,

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

6523-

CRV,

Anticancer effects of Carvone in myeloma cells is mediated through the inhibition of p38 MAPK signalling pathway, apoptosis induction and inhibition of cell invasion

NA,

Melanoma,

20 μM against the myeloma KMS-5 cells

AntiCan↑, carvone exerts significant anticancer effects on the myeloma cancer cells in a dose-dependent manner.
TumCP↓, antiproliferative effects were due to induction of apoptosis and G2/M cell cycle arrest.
Apoptosis↑,
TumCCA↑,
TumCI↓, carvone could inhibit the cell invasion and the expression of p-P38 protein at IC50.
p‑p38↓,

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/PTGS2↓,
NF-kB↓,

6274-

DL,

Protective Effect of D-Limonene against Oxidative Stress-Induced Cell Damage in Human Lens Epithelial Cells via the p38 Pathway

in-vitro,

Nor,

*antiOx↑, It has been shown to have antioxidant effect;
*ROS↓, we found that D-limonene can effectively prevent the oxidative damage caused by H2O2 and propose that the main mechanism underlying the inhibitory effects of D-limonene is the inhibition of HLECs apoptosis.
*Apoptosis↓,
*Casp3↓, reduced the H2O2-induced ROS generation and inhibited the H2O2-induced caspase-3 and caspase-9 activation and decreased the Bcl-2/Bax ratio
*Casp9↓,
*Bax:Bcl2↑,
*p‑p38↓, it inhibited H2O2-induced p38 MAPK phosphorylation.

691-

EGCG,

Preclinical Pharmacological Activities of Epigallocatechin-3-gallate in Signaling Pathways: An Update on Cancer

Review,

NA,

Apoptosis↑,
necrosis↑,
TumAuto↑,
ERK↓, ERK1/2
p38↓,
NF-kB↓,
VEGF↓,

6577-

EU,

Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

in-vitro,

Lung,

A549

Dose↝, Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml.
TumCP↓,
PHB↓, treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX
ANXA1↓,
p38↓,

6391-

Eug,

BCP,

5-FU,

Exploring Mechanism of Actions for Eugenol and Beta-Caryophyllene to Combat Colorectal Cancer Chemotherapy Using Network Pharmacology

in-vitro,

CRC,

HCT116

eff↑, MTT assay revealed in-vitro cytotoxic effects of EUG, BCP, and 5-FU, with a noteworthy reduction in IC50 values observed when combining the compounds, indicating synergistic effects
ChemoSen↑,
HSP90↓, Molecular docking studies indicate that EUG, BCP, and 5-FU effectively inhibit the core target protein HSP90AA1
Dose↝, We aimed to lower the IC50 value of 5-FU (6 to 192.19 µM) by combining it with the three concentrations of EUG and BCP (50 µM, 100 µM, and 200 µM) to reduce its side effects
TumAuto↑, promote autophagy and inhibit apoptosis through PI3K/Akt/mTOR pathway and JNK/P38 pathway, which are key pathways in epithelial to mesenchymal transition inhibition.
Apoptosis↑,
PI3K↓,
Akt↓,
mTOR↓,
JNK↓,
p38↓,
EMT↓,

6843-

EVO,

Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells

in-vivo,

PC,

PANC1

EVO (1.0, 5.0 and 10 µM) for 48 h a

Tumor-bearing nude mice

in-vitro,

PC,

SW1990

Apoptosis↑, Apoptosis increased with increasing EVO concentration.
LC3II↓, EVO decreased LC3II, enhanced P62 and inhibited the expression of Akt, extracellular-signal-regulated protein kinase (ERK)1/2 and p38.
p62↑,
Akt↓,
ERK↓,
p38↓,
TumW↓, tumor weight decreased more markedly in the EVO-treated group.
TumCG↓, EVO markedly inhibited the growth of PC cells.
TumCMig↓, EVO decreases PC cell migration

3714-

FA,

Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review

Review,

AD,

*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/PTGS2↓,
*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,

MCF7

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,

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/PTGS2↓, 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,

*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/KDR/Flk1↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2/BIRC3↓, 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,

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/DDIT3↑, 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,

6916-

FIS,

Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways

in-vitro,

BC,

MCF7

PCK1↓, found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways.
ROS↓,
ERK↓,
MAPK↓,
p38↓,
NF-kB?, furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK

1117-

GBE,

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

rats

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↓,
CCN2/CTGF↓,
E-cadherin↑,
MMP1:TIMP1↑,

7279-

GGB,

Rad,

Radioprotective effect of Ginkgolide B on brain: the mediating role of DCC/MST1 signaling

in-vivo,

Nor,

 C57BL/6 mice were stimulated with an X-ray (20 Gy) to establish an RBI model.

*cognitive↑, X-ray-treated mice exhibited cognitive impairment and depression-like behavior, which was ameliorated by GB treatment.
*radioP↑,
*ROS↓, GB also reduced the ROS production and the number of TUNEL-positive cells in the hippocampus
*p‑Akt↑, GB increased the protein levels of p-AKT and Bcl2, while decreased the protein levels of MST1, p-p38, p-JNK, cleaved-caspase-3 and Bax both in vivo and in vitro.
*Bcl-2↑,
*Mst1↓,
*p‑p38↓,
*JNK↓,
*cl‑Casp3↓,
*BAX↓,

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↓,

7482-

H2,

Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

Review,

Var,

Review,

IBD,

Review,

Stroke,

Review,

Sepsis,

Review,

AD,

Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

7487-

H2,

A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives

Review,

Nor,

*Inflam↓, H2 demonstrates numerous biologically therapeutic properties, including anti-inflammatory, antioxidant, anti-cancer, anti-stress, anti-apoptotic, anti-allergic effects, signaling molecule functions, regulation of redox balance
*antiOx↓,
*Stress↓,
*Dose↝, The administration methods of hydrogen include inhalation, hydrogen-rich water, hydrogen-rich saline, hydrogen-rich eye drops, and hydrogen-rich bathing.
*cardioP↑, graphical abstract and figure 4
*GastroP↑,
*BBB↑, H2 is its ability to easily cross the blood-brain barrier and penetrate biomembranes, diffusing throughout the different tissues and organs.
*eff↑, The above-cited properties led some researchers to refer to it as a "miracle" molecule
*toxicity↓, Regarding the biosafety of hydrogen, numerous reports, including those from the US government and the EU, have indicated that hydrogen is safe for biological systems, showing no acute or chronic toxicity under normal pressure
*Dose↝, human large intestine often produces approximately 70–140 mL of hydrogen daily through the action of coliform bacteria such as Escherichia coli under typical environmental conditions.
*hepatoP↑, including cardioprotective properties, improved liver function, reduced oxidative stress, and prevention of Parkinson's disease
*ROS↓,
*SOD↑, 1.5–2.0 L/day drinking HRW orally 0.55–0.65 mM 1.65–2.6 mg H2/day 8 weeks SOD: ↑ TRABS: ↓ HDL: ↑
*TBARS↓,
*HDL↑,
*LDL↓, figure 4
*Obesity↓, figure 5 obesity
*GSH↑, HRW treatment partially alleviated colitis symptoms, improved histopathological changes, significantly increased glutathione (GSH) concentration, and reduced the level of TNF-α.
*TNF-α↓,
*GutMicro↑, HRW was found to exhibit partial relief of inflammation, oxidative stress, and dysbiosis in the intestinal flora of mice with chronic ulcerative colitis (UC) induced by dextran sulfate sodium (DSS)
*DNAdam↓, HRW-treated mice exhibited decreased levels of markers associated with oxidative DNA damage, such as phosphorylated histone H2AX and 8-hydroxy-2′-deoxyguanosine, as well as markers indicative of aging
*γH2AX↓,
*p‑p38↓, Treatment with HRS also inhibited the activation of p-p38 and NF-κB while suppressing the production of several pro-inflammatory mediators,
*NF-kB↓,

3774-

H2,

The role of hydrogen in Alzheimer’s disease

Review,

AD,

*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,

*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.

7758-

ISL,

Targeting the JAK/STAT pathway with isoliquiritigenin in ovarian cancer: molecular mechanisms and therapeutic implications

Review,

Ovarian,

JAK↓, ISL exerts significant anti-ovarian cancer effects through multitarget regulation of the JAK/STAT pathway.
STAT↓,
toxicity↓, With the advantages of low toxicity and multi-pathway modulation, ISL is a promising natural candidate for targeted therapy,
*antiOx↑, exhibits significant antioxidant capacity, effectively scavenging free radicals and reducing oxidative stress-induced cellular damage
*ROS↓,
*NRF2↑, By activating the Nrf2/ARE signaling pathway, ISL induces the expression of antioxidant enzymes such as HO-1 and NQO1, thereby enhancing cellular antioxidant defense systems
*ARE↑,
*HO-1↑,
*NQO1↑,
*Inflam↓, Regarding anti-inflammatory effects, ISL suppresses NF-κB and MAPK signaling pathways, reducing inflammatory factor production and alleviating inflammatory responses
*NF-kB↓,
*MAPK↓,
*SOD↑, it maintains intracellular antioxidant defense mechanisms, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity to mitigate oxidative stress-induced cellular damage
*Catalase↑,
*GPx↑,
*AntiViral↑, Its antiviral activity manifests as ISL’s ability to disrupt viral replication cycles, inhibit viral protein synthesis, and suppress multiple viruses.
*NADPH↑, ISL reduces ROS production by activating the Nrf2 pathway or upregulating NADPH oxidase expression and activity
ROS↓, In SK-MEL-28 melanoma cells, ROS inhibition suppressed p38α (Thr180/Tyr182) phosphorylation, blocked the p38-mTOR-STAT3 (Ser727) cascade. This leads to decreased STAT3 transcriptional activity, silencing downstream cyclin D1 and survivin expression,
p38↓,
mTOR↓,
STAT3↓,
cycD1/CCND1↓,
survivin↓,
p38↑, ISL inhibits autophagy flux in pancreatic cancer cells by activating the p38-MAPK signaling pathway,
MAPK↑,
mtDam↑, This mechanism disrupts cellular clearance of damaged mitochondria, triggers endoplasmic reticulum stress and oxidative stress, ultimately inducing apoptosis.
ER Stress↑,
ROS↑,
Apoptosis↑,
GLUT4↓, chemically synthesized derivative ISL-17 in MKN45 gastric cancer cells interferes with energy metabolism (Warburg effect) by inhibiting GLUT4-mediated glucose uptake, leading to decreased ATP levels and increased ROS accumulation.
ATP↓,
Glycolysis↓, This process triggers an energy crisis by blocking glycolysis and oxidative phosphorylation, further enhancing the cytotoxic effects of ROS and thereby inhibiting tumor growth
eff↑, Combining ISL with mTOR inhibitors significantly enhances growth inhibition of ovarian cancer cells by dual blockade of the PI3K/Akt/mTOR pathway

7873-

isoO,

Isoorientin attenuates doxorubicin-induced cardiac injury via the activation of MAPK, Akt, and Caspase-dependent signaling pathways

in-vitro,

Liver,

HepG2

in-vitro,

CRC,

HT-29

in-vitro,

Lung,

A549

ChemoSen↑, The antiproliferation of DOX on Hela, HepG2, HT-29, and A549 cells could be increased synergistically when cotreated with ISO in vitro. I
TumCP↓,
chemoP↑, ISO could also improve the survival rate of DOX-injured cardiomyocytes by reducing reactive oxygen species, maintaining mitochondrial function, and inhibiting apoptosis.
*ROS↓,
*mtDam↓,
*Apoptosis↓,
*cardioP↑, In mice receiving DOX, a protective effect on myocardial tissue, which was reflected by improved survival state of mice receiving chemotherapy, was observed.
*NRF2↑, ISO upregulated Nrf2 and TGF-β3 by downregulating the phosphorylation levels of JNK and p38 proteins on the MAPK pathway and the Akt and Stat3 expression levels.
*TGF-β↑,
*p‑JNK↓,
*p‑p38↓,
*MAPK↝,
*Akt↝,
*STAT3↝,

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/PTGS2↓,
*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,

10, 30, and 50 µg/mL

peripheral blood endothelial progenitor cells cultivated with high glucose

*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/PTGS2↓,
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

mouse

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,

 0.2T, 4Hz

 reduced aluminum deposition in the brains of AD mice

*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)
*ARG1/2↑, 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,

*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/PTGS2↓,
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,

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/PTGS2↓,
GLO-I↓,
CYP1A1↑,
lipid-P↓,
p‑Akt↓,
p‑mTOR↓,
VCAM-1↓,
P-gp/ABCB1↓,
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↓,

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,

500 mg/day

50 women with RA

*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

 0, 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, and 400 µg/mL

50ug/L @ 72h

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↓,

Showing Research Papers: 1 to 50 of 68
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 68

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,
Total Targets: 255

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

compII↑, 1, Stress↓, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 11, ARE↑, 2, Bil↑, 1, Catalase↑, 5, Fenton↓, 1, Ferroptosis↓, 1, GCLC↑, 1, GCLM↑, 1, GPx↑, 2, GSH↑, 4, HDL↑, 1, HO-1↑, 4, lipid-P↓, 4, MDA↓, 5, MPO↓, 2, NQO1↑, 2, NRF2↑, 7, RNS↓, 1, ROS↓, 18, ROS∅, 1, SOD↑, 7, TBARS↓, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

FTH1↑, 1, IronCh↑, 1, TfR1/CD71↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1, compIII↑, 1, p‑MKK4↑, 1, MMP↑, 1, mtDam↓, 2,

Core Metabolism/Glycolysis(tgid=4) ⓘ

12LOX↓, 1, ALAT↓, 1, AMPK↑, 2, LDL↓, 2, NADPH↑, 1, PPARγ↑, 1, SIRT1↑, 2,

Cell Death(tgid=5) ⓘ

Akt↓, 1, Akt↑, 4, Akt↝, 1, p‑Akt↑, 1, APAF1↓, 1, Apoptosis↓, 2, BAX↓, 2, Bax:Bcl2↑, 1, Bcl-2↑, 2, Casp12↓, 1, Casp3↓, 2, cl‑Casp3↓, 1, Casp9↓, 2, Ferroptosis↓, 1, GranB/GZMB↓, 1, iNOS↓, 4, JNK↓, 8, p‑JNK↓, 6, MAPK↓, 5, MAPK↝, 1, p‑MAPK↓, 1, p38↓, 12, p‑p38↓, 9,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1, p‑eIF2α↓, 1, ER Stress↓, 1, GRP78/BiP↓, 1, XBP-1↓, 1,

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, LC3B↑, 1, p62↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1, P53↓, 1, γH2AX↓, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 2, ERK↑, 2, p‑ERK↓, 2, FOXO↑, 1, FOXO3↑, 1, GSK‐3β↑, 1, Mst1↓, 1, mTOR↓, 1, PI3K↑, 2, STAT1↓, 1, STAT3↝, 1, STAT4↓, 1,

Migration(tgid=13) ⓘ

5LO↓, 1, AP-1↓, 1, APP↓, 1, ARG1/2↑, 1, Ca+2↓, 1, heparanase↑, 1, MMP1↓, 1, MMP2↓, 1, MMP3↓, 1, Rac1↑, 1, RAGE↓, 1, TGF-β↑, 2, TGF-β1↑, 1, TIMP2↑, 1, uPA↓, 1, VCAM-1↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1, ATF4↓, 1, NO↓, 2, NO↑, 1, VEGF↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2, GastroP↑, 1, IBI↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1, COX1↓, 1, COX2/PTGS2↓, 4, ICAM-1↓, 1, IFN-γ↓, 1, p‑IKKα↓, 1, IL1↓, 1, IL10↑, 2, IL1β↓, 5, IL4↓, 1, IL4↑, 1, IL6↓, 8, IL8↓, 2, Imm↑, 1, Inflam↓, 12, p‑IκB↓, 1, LPS↓, 1, MyD88↓, 1, NF-kB↓, 10, p‑p65↓, 1, PGE2↓, 2, PGE2↑, 1, Th1 response↓, 2, Th17↓, 1, Th2↑, 2, TLR4↓, 1, TNF-α↓, 8,

Synaptic & Neurotransmission(tgid=18) ⓘ

ADAM10↑, 1, BChE↓, 1, BDNF↑, 3, ChAT↑, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 5, BACE/β-secretase↓, 2, NLRP3↓, 4,

Hormonal & Nuclear Receptors(tgid=20) ⓘ

ER(estro)↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1, BioAv↝, 1, BioEnh↑, 1, Dose↝, 5, eff↑, 2, Half-Life↝, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1, Bil↑, 1, creat↓, 1, GutMicro↑, 3, IL6↓, 8, RAGE↓, 1, Urea↓, 1,

Functional Outcomes(tgid=23) ⓘ

antiPs↑, 1, cardioP↑, 5, cognitive↑, 7, hepatoP↑, 4, memory↑, 5, motorD↑, 1, neuroP↑, 9, Obesity↓, 2, Pain↓, 1, radioP↑, 2, RenoP↑, 2, toxicity↓, 2, toxicity∅, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1, Inf↓, 1, Sepsis↓, 1,
Total Targets: 178

Scientific Paper Hit Count for: p38, p38

6 Fisetin
4 Hydrogen Gas
4 Quercetin
4 Silymarin (Milk Thistle) silibinin
3 Artemisinin
3 Curcumin
3 Lycopene
3 Shikonin
2 Berberine
2 Beta-Caryophyllene
2 Caffeic acid
2 5-fluorouracil
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 α-Bisabolol / Chamomile oil
1 Carvone
1 Resveratrol
1 Ginger/6-Shogaol/Gingerol
1 D-limonene
1 EGCG (Epigallocatechin Gallate)
1 Eurycomanone
1 Eugenol
1 Evodiamine
1 Ferulic acid
1 Ginkgo biloba
1 Ginkgolide B
1 Radiotherapy/Radiation
1 Grapeseed extract
1 Isoliquiritigenin
1 isoorientin
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 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
  wNotes=on  sortOrder:rid,rpid

p38 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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