IL8 Cancer Research Results

IL8, Interleukin-8: Click to Expand ⟱

Source:

Type:

Interleukin-8 (IL-8), also known as CXCL8, is a chemokine primarily involved in the recruitment and activation of neutrophils. Its role in cancer is significant, as it can influence tumor growth, metastasis, and the tumor microenvironment.
IL-8 is a chemokine frequently produced in the tumor microenvironment by human malignant cells. IL-8 plays key roles in the immunobiology of human malignancies and resistance to treatments. Circulating IL-8 concentration reflects tumor burden.

In many cancers have elevated levels of IL-8 and are associated with increased tumor aggressiveness, metastasis, and poorer overall survival. Elevated IL-8 often correlates with a more inflammatory tumor microenvironment, which can facilitate tumor progression.

Scientific Papers found: Click to Expand⟱

2659-

AL,

Allicin inhibits spontaneous and TNF-α induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells

in-vitro,

HCC,

HT29

in-vitro,

HCC,

Caco-2

IL1β↓, Allicin markedly inhibited the spontaneous and TNF-α -induced secretion of IL-1β, IL-8, IP-10 and MIG from the two different cell lines in a dose-dependent manner and suppressed the expression of IL-8 and IL-1β mRNA levels
IL8↓,
Inflam↓, allicin may have the potential to attenuate intestinal inflammation.

2660-

AL,

Allicin: A review of its important pharmacological activities

Review,

AD,

Review,

Var,

Review,

Park,

Review,

Stroke,

*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2/PTGS2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2/KDR/Flk1↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

3450-

ALA,

α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells

in-vitro,

NA,

AGS

*IL8↓, α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells
*MAPK↓,
*JAK↓,
*STAT↓,
*NF-kB↓,

1159-

And,

Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism

Review,

NA,

NRF2↑,
COX2/PTGS2↓,
IL6↓,
IL8↓,
IL1↓, IL-1β
iNOS↓,
MPO↓,
TNF-α↓,
VEGF↓,
Hif1a↓,
p‑AMPK↑,

2639-

Api,

Plant flavone apigenin: An emerging anticancer agent

Review,

Var,

*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27/CDKN1B↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2/PTGS2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

3382-

ART/DHA,

Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?

Review,

Var,

1.20–15.2 μM

AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2/PTGS2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

3391-

ART/DHA,

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Review,

Var,

TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27/CDKN1B↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2/PTGS2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

3165-

Ash,

Inhibitory effect of withaferin A on Helicobacter pylori‑induced IL‑8 production and NF‑κB activation in gastric epithelial cells

in-vitro,

Nor,

gastric epithelial cells

*IL8↓, WA efficiently reduced IL-8 production by AGS cells in response to H. pylori infection. H. pylori-induced activation of NF-κB, but not MAPKs, was also inhibited by pre-treatment of WA in the cells.
*Inflam↓, therapeutic agent for H. pylori-mediated gastric inflammation

3166-

Ash,

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives

Review,

Var,

*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

5419-

ASTX,

Astaxanthin and other Nutrients from Haematococcus pluvialis—Multifunctional Applications

Review,

Nor,

*antiOx↑, extraction of astaxanthin and analysis of its antioxidant, anti-inflammatory, anti–diabetic and anticancer activities.
*Inflam↓,
*AntiDiabetic↓,
AntiCan↑,
*lipid-P↓, astaxanthin is more effective than β-carotene in the prevention of lipid peroxidation.
TumCP↓, Studies have reported that astaxanthin not only inhibits the proliferation of colon cancer cells but can also cause their apoptosis
Apoptosis↑,
TumCCA↑, Astaxanthin was included in the extract and was responsible for stopping the progression of the cell cycle and promoting the apoptosis [95].
*SOD↑, Astaxanthin also increased SOD activity and decreased PG-E2, LT-B4, NO, IL-8 and IFN- γ production [103,104,105].
*PGE2↓,
*NO↓,
*IL8↓,
*IFN-γ↓,
*cardioP↑, Astaxanthin has a cardiovascular protective effect in animals, but there is a lack of research supporting the therapeutic benefit of astaxanthin in atherosclerotic cardiovascular disease in humans.
*NF-kB↓, Oral supplementation with astaxanthin in rats after surgery decreased the expression of NF-KB and TNF-α,
*TNF-α↓,
*BioAv↑, Satisfactory astaxanthin bioavailability results were obtained with a daily astaxanthin dose of 40 mg/day.

4981-

ATV,

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

Apoptosis↑, The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity.
selectivity↑,
eff↑, Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.
HMG-CoA↓, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, are a commonly used and well-tolerated class of drugs used in lipid disorders,
*cardioP↑, Their effectiveness in preventing the development of cardiovascular diseases makes statins one of the most widely used drugs
OS↑, On the other hand, improved survival in patients with hepatocellular carcinoma, colon cancer or prostate cancer is visible after the use of any statin
IL1β↓, statins inhibit the synthesis of cytokines, including interleukin (IL-) IL-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α)
IL6↓,
IL8↓,
TNF-α↓,
TumAuto↑, Simvastatin-induced autophagy has been reported in rhabdomyosarcoma cells [
Histones↝, Statins are also involved in the regulation of the histone acetylation level.
ac‑H3↑, Studies indicate that statins increase histone H3 and H4 acetylation as well as inhibit class I and II HDACs
ac‑H4↑,
HDAC↓,

2694-

BBR,

Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells

in-vitro,

BC,

IL8↓, BBR dramatically suppresses IL-8 expression.
TumCI↓, BBR also inhibited cell invasiveness
EGFR↓, BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation.
MEK↓,
ERK↓,
TGF-β1↓, BBR inhibits the tumorigenic and angiogenic properties of TNBC cells by inhibiting TGF-β1 expression and VEGF secretion (
VEGF↓,

2749-

BetA,

Anti-Inflammatory Activities of Betulinic Acid: A Review

Review,

Nor,

Inflam↓, betulinic acid as a promissory lead compound with anti-inflammatory activity
*NO↓, BA can inhibit the production of NO, mainly in macrophages cultures stimulated with bacterial lipopolysaccharide (LPS) and/or interferon gamma (IFN-ɣ)
*IL10↑, (BA) has a broad-spectrum anti-inflammatory activity, significantly increasing IL-10 production, decreasing ICAM-1, VCAM-1, and E-selectin expression and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB),
*ICAM-1↓,
*VCAM-1↓,
*E-sel↓,
*NF-kB↓,
*IKKα↓, BA blocks the NF-κB signaling pathway by inhibiting IκB phosphorylation and d
*COX2/PTGS2↓, BA also inhibits cyclooxygenase-2 (COX-2) activity and, therefore, decrease prostaglandin E2 (PGE2) synthesis
*PGE2↓,
*IL1β↓, The production of critical pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8, IL-12, and TNF, is also decreased by BA treatment
*IL6↓,
*IL8↓,
*IL12↓,
*TNF-α↑,
*HO-1↑, induction of HO-1 enzyme activity is associated with the anti-inflammatory effect of BA, since SnPP, an inhibitor of HO-1, promoted a partial reversal of BA’s effect on NF-κB activity,
*IL10↑, BA also increased the amount of IL-10, a well-known anti-inflammatory cytokine
*IL2↓, decreasing the production of pro-inflammatory cytokines, such as IL-2, IL-6, IL-17, and IFN-γ
*IL17↓,
*IFN-γ↓,
*SOD↑, BA decreased the production of the inflammatory mediators described above at the inflammation site and increased enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver
*GPx↑,
*GSR↑,
*MDA↓, BA decreased malondialdehyde (MDA) levels, a key mediator of oxidative stress and widely used as a marker of free radical mediated lipid peroxidation injury, at the inflammation site
*MAPK↓, BA downregulates MAPK signaling pathways (ERK1/2, JNK, and p38) in the paw edema tissue, which, in part, explains the inhibition of cytokine production (IL-1β and TNF), COX-2 expression, and PGE2 production (Figure 3).

3520-

Bor,

Effect of boron element on photoaging in rats

in-vivo,

NA,

rats

*hepatoP↑, to positively affect the liver metabolism, and to promote bone density, embryogenic development and wound healing, and is known to provide significant benefits in cancer treatment through neutron capture systems
*BMD↑,
*COX2/PTGS2↓, Increased skin inflammatory parameters (COX-2, IL-8, NF-KB, IL-6, and TNF-α) levels in UVB-exposed groups were inhibited in all treatment groups
*IL8↓,
*NF-kB↓,
*IL6↓,
*TNF-α↓,

6557-

BSB,

Alpha-bisabolol protects against neonatal asthma by suppressing airway inflammatory signaling

in-vivo,

Nor,

rats

*ROS↓, AB significantly decreased mucous gland hypertrophy, eosinophil infiltration, and oxidative stress marker levels in the allergic airway inflammation-induced AB-pretreated rats.
*Inflam↓, AB pretreatment significantly reduced the levels of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, IL-17, monocyte chemoattractant protein-1, C-X-C chemokine receptor type 4 (CXCR4), and thymic stromal lymphopoietin, which were i
*IL1β↓,
*IL6↓,
*IL8↓,
*IL17↓,
*CXCR4↓,
*COX2/PTGS2↓, transcription of cyclooxygenase-2, tumor necrosis factor-α, CXCR4, toll-like receptor 4, Eotaxin-1, and regulated upon activation normal T cell expressed and secreted were significantly suppressed in allergic airway inflammation-induced AB-pretreated
*TLR4↓,
*NO↓, NO, PCO, MDA, and XO, all of these oxidative stress parameters were significantly attenuated in AB-treated allergic airway inflammation-induced rat pups
*MDA↓,
*XO↓,

5742-

Buty,

Butyrate: A Double-Edged Sword for Health?

Review,

Var,

HCAR2↑, Another major GPCR activated by butyrate is GPR109A (
Inflam↓, anti-inflammatory properties of butyrate are also achieved through inhibition of the production of proinflammatory enzymes and cytokines
HDAC↓, Butyrate functions as an HDAC inhibitor
*IFN-γ↓, animal studies reported that the proinflammatory cytokines IFN-γ, TNF-α, IL-1β, IL-6, and IL-8 are inhibited, whereas IL-10 and TGF-β are upregulated in response to butyrate
*TNF-α↓,
*IL1β↓,
*IL6↓,
*IL8↓,
*IL10↑,
*LTA/TNF-β↑,
*NF-kB↓, butyrate is at least in part due to inhibition of the activation of a transcription factor known as NF-κB (
*ROS↓, by rescuing the redox machinery and controlling reactive oxygen species,
PPARγ↓, Further studies also showed that butyrate is capable of activating PPAR-γ (67), which is a member of the nuclear hormone receptor family and highly expressed in colonic epithelial cells,
Weight↓, although a large body of evidence has suggested the effect of butyrate on alleviating high fat diet–induced obesity and insulin resistance, a few studies showed an opposite effect.

6083-

CHOC,

Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

Review,

Colon,

ROS↓, Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells
Inflam↓,
TumCP↓,
Apoptosis↑,
*Dose↝, highest flavanol content of all foodstuffs on a weight basis and is a significant contributor to the total dietary intake of flavonoids
*BioAv↓, comparison to other flavonoid-containing foodstuffs, cocoa and its derivative products exhibit a high concentration of larger procyanidins that are poorly absorbed through the gut barrier,
*BioAv↑, hose oligomers and polymers of flavanols that are not absorbed in the intestine could be metabolized by the microbiota into low molecular weight phenolic acids, which are more bioavailable, and might be well absorbed through the colon
GSH↑, Caco-2 10 µg/mL acrylamide-incubated cells: ↓ GSH depletion, ↓ ROS generation, ↑ γ-GCS, ↑ GST
GSTs↑,
PGE2↓, Caco-2 50 µM (gallic acid equivalents, 14.5 µg/mL) ↓ PGE2, ↑ COX-1,
COX1↑,
IL8↓, Caco-2 10 µg/mL TNF-treated cells: ↓ IL-8, ↓ COX-2, ↓ iNOS, ↓ NFκB activation
COX2/PTGS2↓,
iNOS↓,
NF-kB↓,
chemoP↑, This review reports the potential chemopreventive actions of cocoa and its main flavanols against colon cancer

6181-

Cro,

Crocetin: A Systematic Review

Review,

Var,

Review,

AD,

cardioP↑, According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties.
hepatoP↑,
*neuroP↑,
AntiCan↑,
*AntiDiabetic↑,
*memory↑,
*BioAv↓, poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin.
*ROS↓, Crocetin can act via different mechanisms, such as enhancing the rate of oxygen transport and diffusivity, inhibiting pro-inflammatory mediators, protecting cells from reactive oxygen species (ROS) damage, and stimulating apoptosis in cancer cells
Apoptosis↑,
*lipid-P↓, Myocardial hypertrophy rats Decreases the LPO content and increases the activities of GSH-Px and SOD
*SOD↑,
SOD↓, MCF-7 cells Crocetin (200 μmol/L) Inhibits SOD activity by affecting copper binding sites
ERα/ESR1↓, MCF-7 cells Crocetin glucosyl ester IC50 from 31.25 to 1,000 μg/ml Inhibits estrogen receptor α and HDAC2 mediated signaling cascade
HDAC2↓,
TumCCA↑, KYSE-150 cells Crocetin (0, 12.5, 25, 50, 100, 200 μmol/L) S-phase cell arrest
Bax:Bcl2↑, AGS cells Crocetin (50–240 μmol/L) Decreases the Bcl-2/Bax ratio of AGS cells
IL6↓, HCT116 cells Crocetin (30 µM) Downregulates inflammation-related genes, HMGB1, IL-6, and IL-8
IL8↓,
Shh↓, Cancer stem cells (CSC) Inhibits the expression of Sonic hedgehog (SHH)
COX2/PTGS2↑, HeLa cells Upregulates COX-2 expression
*GSK‐3β↓, Alzheimer’s disease (AD) SH-SY5Y and PC12 cells Inhibits the active forms of GSK3β and ERK 1/2 kinases and significantly reduces the total tau protein and tau protein phosphorylation
*ERK↓,
*tau↓,
*ROS↓, crocetin-induced inhibition of Aβ1-42-induced hippocampal HT22 cell death could be mediated via reduced ROS production.
*GSTs↑, The activities of antioxidant enzymes [GSH-Px, GSH reductase (GR), GST, CAT, and SOD]
*Catalase↑,
*SOD↑,
*BioAv↑, The bioavailability of crocetin can be improved by formulating a crocetin injection

6309-

Cro,

Crocin exerts anti-tumor effect in colon cancer cells via repressing the JaK pathway

in-vitro,

CRC,

HCT116

tumCV↓, while crocin restrained the HCT-116 cells vitality, proliferation and the expression of Ki-67, while inducing apoptosis in a concentration-dependent manner.
TumCP↓,
Ki-67↓,
Apoptosis↓,
Inflam↓, inflammation- and oxidative- related factors in HCT-116 cells were largely blunted by crocin that enhanced ROS, restrained the MMP and suppressed p-JAK2/JAK2, p-STAT3/STAT3, and p-ERK/ERK expression
ROS↑,
MMP↓,
JAK2↓,
STAT3↓,
ERK↓,
MIP2↓, we found that crocin manifested an obvious inhibition of the contents of MIP-2, IL-6, MCP-1, IL-8, IL-1β, and TNF-α in HCT-116 cells in relative to the control group and the inhibitory effect of 200 μM
IL6↓,
MCP1/CCL2↓,
IL8↓,
IL1β↓,
TNF-α↓,
SOD↓, oxidative stress-related factors and confirmed that the contents of SOD, CAT, and GSH in HCT-116 cells were reduced by crocin in relative to the control group and the 200 μM
Catalase↓,
GSH↓,
ROS↑, crocin exhibited a notable increase production of ROS in HCT-116 cells
mtDam↑, crocin is inducing oxidative stress and damaging the mitochondria, leading to cell death.

6303-

Cro,

Crocetin treatment inhibits proliferation of colon cancer cells through down-regulation of genes involved in the inflammation

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

DU145

NF-kB↓, Treatment of the DU-145 cells with crocetin caused a significant reduction in the expression levels of NF-κB, VEGF and MMP-9.
VEGF↓,
MMP9↓,
Inflam↓, significant reduction in the expression of genes involved in inflammation including, HMGB1, IL-6 and IL-8 on treatment of DU-145 cells with crocetin.
HMGB1↓,
IL6↓,
IL8↓,
TumCG↓, Crocetin inhibits growth of colon cancer cells and prevents tube formation through induction of apoptosis.
Apoptosis↑,

6531-

CRV,

D-carvone attenuates LPS-induced acute lung injury via TLR4/NF-κB and Nrf2/HO-1 signaling pathways in rats

in-vivo,

Nor,

10 or 20 mg/kg D-carvone

Rats

*TRAF1↓, upregulation of pro-inflammatory markers (TLR4, IL-1β, TNF-α), and oxidative stress (increased MDA, decreased GSH and SOD). Treatment with D-carvone at both doses significantly attenuated these changes.
*IL1β↓,
*TNF-α↓,
*ROS↓,
*MDA↓,
*GSH↑,
*SOD↑,
*Inflam↓, D-carvone downregulated pro-inflammatory markers, upregulated anti-inflammatory (NRF2) and anti-apoptotic (Bcl-2) proteins, and reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8) in lung tissues
*NRF2↑,
*Bcl-2↑,
*IL8↓,
*antiOx↑, D-carvone protects against LPS-induced ALI in rats, possibly through its anti-inflammatory and antioxidant properties.

4650-

CUR,

Curcumin and cancer stem cells: curcumin has asymmetrical effects on cancer and normal stem cells

Review,

Var,

SCD1↓, Curcumin has been shown to have numerous cytotoxic effects on cancer stem cells (CSCs).
IL6↓, This is due to its suppression of the release of cytokines, particularly interleukin (IL)-6, IL-8 and IL-1
IL8↓,
IL1↓,
*selectivity↑, curcumin has little toxicity against normal stem cells (NSCs).
Wnt↝, effects at multiple sites along CSC pathways, such as Wnt, Notch, Hedgehog and FAK.
NOTCH↝,
HH↝,
FAK↝,

3588-

CUR,

The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies

Review,

AD,

*cognitive↝, Clinical studies are mixed regarding curcumin’s effects on cognitive deficits.
*BioAv↑, Ways to improve curcumin’s bioavailability are required.
*Inflam↓, anti-inflammatory activity can be attributed to the suppression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes via down-regulation of nuclear factor kappa B (NF-κB)
*COX2/PTGS2↓,
*iNOS↓,
*NF-kB↓,
*TNF-α↓, nhibition of several inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a) or interleukin (IL) -1, -2, -6, -8, and -12 (
*IL1↓,
*IL2↓,
*IL6↓,
*IL8↓,
*IL12↓,
*ROS↓, Curcumin’s ability to scavenge free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), provides its antioxidant capacity
*RNS↓,
*antiOx↑,
*BBB↑, Multiple studies in rodents and humans have shown that curcumin crosses the blood brain barrier (BBB)
*BioAv↓, drawback is the low bioavailability due to poor solubility, low absorption, rapid metabolism, and rapid excretion
*cognitive↑, The researchers detected a significant cognitive improvement at both doses compared to the untreated group, while a significant dose-response effect was found throughout time with higher doses of curcumin producing greater cognitive improvement
*memory↑, supplementation may improve memory and result in a number of biochemical alternations leading to suppressed tau aggregation
*tau↓,
*eff↑, Combined curcumin and piperine showed superiority, in a dose dependent manner,

1418-

CUR,

Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis

Review,

Arthritis,

*COX2/PTGS2↓, Curcumin downregulates the cyclooxygenase-2 (COX-2) pathway, reducing the production of prostaglandins associated with inflammation
*Inflam↓,
*5LO↓, directly inhibits lipoxygenase (LOX)
*NO↓,
*NF-kB↓,
*TNF-α↓,
*IL1↓,
*IL2↑,
*IL6↓,
*IL8↓,
*IL12↓,
*MCP1/CCL2↓,
*PGE2↓,
*MMP2↓,
*MMP3↓,
*MMP9↓,
*NLRP3↓,
*ROS↓, arthritis(basically normal cell)

13-

CUR,

Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action

Review,

BC,

P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2/PTGS2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

6211-

CUR,

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer

Review,

Var,

HIF-1↓, Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF).
VEGF↓, Curcumin suppresses the HIF-1 pathway under hypoxia, which decreases VEGF expression in both tumour and stromal cells and suppresses angiogenesis.
angioG↓, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia.
RadioS↑, continued interest in curcumin is the molecules’ modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours.
ChemoSen↑, Combining cisplatin with curcumin promotes cell apoptosis through the YWHAG pathway and its interaction with HIF-1α, affecting the pentose phosphorylation pathway [
other↝, Cancer patients with hypoxia in their tumours have a poorer prognosis and are at greater risk of metastasis
Apoptosis↑, Curcumin exerts its unique anti-tumour efficacy primarily via pleiotropic functions resulting in apoptosis and decreased tumour cell growth and metastasis
TumCG↓,
TumMeta↓,
BioAv↓, However, due to its low water solubility and low chemical stability, curcumin’s use is limited.
COX2/PTGS2↓, abrogate the proliferation of pancreatic cancer cells through inhibition of COX-2, CD-31, VEGF, and IL-8 and suppression of TGF-β via NF-κB and HIF-1α downregulation
CD31/PECAM-1↓,
IL8↓,
TGF-β↓,
NF-kB↓,
JAK2↓, Curcumin application reduced tumourspheres of H460 cells via inhibition of the JAK2/STAT3 signalling pathway
STAT3↓,

6216-

CUR,

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials

Review,

Var,

TumCG↓, Curcumin can prevent tumor growth, angiogenesis, epithelial–mesenchymal transition, invasion, and metastasis by modulating the expression of tumor-related non-coding RNA (ncRNA)
angioG↓,
EMT↓,
TumCI↓,
TumMeta↓,
*GutMicro↑, curcumin plays a crucial role in regulating the gut microbiota via biotransformation of curcumin and its metabolites.
*BioAv↓, one of the primary drawbacks of taking curcumin alone is its low bioavailability, which appears to be caused by poor absorption, fast metabolism, and excretion
*HO-1↑, Curcumin is an efficient inducer of hemoxygenase-1 and a powerful inhibitor of reactive oxygen-generating enzymes, such as cyclooxygenase (COX), inducible nitric oxygen synthase (iNOS), lipoxygenase, and xanthine dehydrogenase/oxidase
*ROS↓,
*COX2/PTGS2↓,
*iNOS↓,
PKCδ↓, Curcumin is also a powerful inhibitor of protein kinase C (PKC), tyrosine kinase, epidermal growth factor receptor (EGFR), and IB kinase.
EGFR↓,
NF-kB↓, It suppresses NF-κB activation and the expression of oncogenes, such as c-jun, c-fos, c-myc, Akt, PI3K, cyclin-dependent kinase (CDK)
cJun↓,
cFos↓,
cMyc↓,
Akt↓,
PI3K↓,
CDK4↓,
*TNF-α↓, Continuous supplementation with nanocurcumin (two 40 mg capsules/day after a meal) for 3 months suppressed expression of inflammatory tumor necrosis factor-alpha (TNF-α), high sensitive protein with C-reactive protein (CRP), and interleukin-6 (IL-6)
*CRP↓,
*IL6↓,
MMP9↓, curcumin suppressed metastasis to the lung by suppressing NF-κB, MMP-9, COX-2, and vascular endothelial growth factor (VEGF) expression.
VEGF↓,
JAK↓, Curcumin remarkably inhibits JAK/STAT signaling by downregulating pro-inflammatory interleukins, such as IL-1, IL-2, IL-6, IL-8, IL-12, and MCP-1.
STAT↓,
IL1↓,
IL2↓,
IL6↓,
IL8↓,
IL12↓,
MCP1/CCL2↓,
Apoptosis↑, It promotes apoptosis and ER stress by targeting phosphorylated protein kinase-like ER-resident kinase,
ER Stress↑,
5LO↓, inhibiting lipoxygenase and xanthine oxidase activity
XO↓,
*NRF2↑, The expression of nuclear factors erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) is boosted by curcumin
*HO-1↑,
*AChE↓, Curcumin also inhibits the key enzyme acetylcholinesterase (AChE) and p300, a positive regulator of the Wnt/β-catenin pathway
*neuroP↑, Curcumin has also been suggested to prevent and cure neurotoxicity by replenishing dopamine and 3,4-dihydroxyphenylacetic acid levels.
*glucose↓, remarkably lowers blood glucose levels and improves insulin resistance by reducing hepatic glucose synthesis, inhibiting inflammatory reactions produced by hyperglycemia,
*GLUT2↑, boosting glucose transporters 2 (GLUT2), 3 (GLUT3), and 4 (GLUT4) gene expression, enhancing glucose uptake, and activating the AMPK signaling pathway.
*GLUT3↑,
*GLUT4↑,
*GlucoseCon↑,
*AMPK↑,
*BMD↑, Supplementation with nanomicelle curcumin (80 mg) alone or in combination with Nigella sativa oil (1000 mg) for 2–6 months increased plasma levels of miRNA-21 in postmenopausal women with low bone mass density.
*MDA↓, (1000 mg/day) for 8 weeks reduced serum levels of malondialdehyde (MDA) and high-sensitivity CRP (hs-CRP) and increased the total antioxidant capacity in 81 healthy postmenopausal women
*eff↑, Loriczova et al. demonstrated that iron (18 mg and 65 mg) supplementation along with curcumin (500 mg) reduces iron-induced systemic inflammation by reducing plasma levels of TNF-α
eff↑, high-dose vitamin C (25–100 g/day) along with oral nutrient supplementation including curcumin (1–3 g/day) had improved QoL and survival
P53↑, Curcumin was also reported to induce p53 and Bax expression in patients with colorectal cancer, causing apoptosis and DNA fragmentation and suppressing TNF-α and Bcl-2.
BAX↑,
DNAdam↑,
Bcl-2↓,
CSCs↓, The combination of curcumin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in colorectal liver metastases reduced stem cell markers, such as aldehyde dehydrogenase and CD133.
ALDH↓,
CD133↑,

6672-

Deg,

Deguelin, an Akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice

vitro+vivo,

CRC,

COLO205

in-vitro,

CRC,

HCT116

Akt↑, Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers.
AntiTum↑,
IL8↓, Deguelin significantly inhibited IL-8 gene expression, IκB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells.
p‑IKKα↓,
NF-kB↓,
TumCD↑, Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner.
Apoptosis↑,
cFLIP↓, Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-X(L).
Bcl-2↓,
Bcl-xL↓,
TumVol↓, colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher.

6721-

DHCA,

Dihydrocaffeic Acid—Is It the Less Known but Equally Valuable Phenolic Acid?

Review,

Nor,

*ROS↓, protective effect of DHCA and its derivatives on cells subjected to oxidative stress and inflammation were acknowledged.
*Inflam↓,
*eff↑, Phenolic compounds are undoubtedly one of the most valuable substances that we intake with food.
*other↝, The formation of dihydrocaffeic acid due to the fermentation processes of lactic acid bacteria was also observed in varied sourdoughs (wheat or sorghum), cherry juices, and fermented milk enriched with an extract from the leaves of Cudrania tricuspid
*IL1β↓, DHCA reduced the expression levels of IL-1b, IL-8, and TNF-α.
*IL8↓,
*TNF-α↓,

27-

EA,

Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice

in-vivo,

PC,

PANC1

 PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA

HH↓,
Gli1↓, EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1.
GLI2↓,
CDK1/2/5/9↓,
p‑Akt↓,
NOTCH1↓,
Shh↓,
Snail↓,
E-cadherin↑,
NOTCH3↓,
HEY1↓,
TumCG↓, EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage.
TumCP↓,
Casp3↑,
cl‑PARP↑,
Bcl-2↓, EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
BAX↑,
COX2/PTGS2↓, EA inhibited the markers of angiogenesis (COX-2, HIF1α, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues.
Hif1a↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
IL6↓,
IL8↓,
MMP2↓,
MMP9↓,
NA↓, EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways

6613-

Ech,

Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system

Study,

Nor,

*TNF-α↓, Both E. purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation of TNF-alpha and IL-8 in LPS pre
*IL8↓,
Imm↑, the study shows that the formulations trigger the same effects on the measured immune parameters.

3201-

EGCG,

Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential

Review,

NA,

*AntiCan↑, EGCG’s therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes
*cardioP↑,
*neuroP↑,
*BioAv↝, Factors such as fasting, storage conditions, albumin levels, vitamin C, fish oil, and piperine have been shown to affect plasma concentrations and the overall bioavailability of EGCG
*BioAv↓, Conversely, bioavailability is reduced by processes such as air oxidation, sulfation, glucuronidation, gastrointestinal degradation, and interactions with Ca2+, Mg2+, and trace metals,
*BioAv↓, EGCG’s oral bioavailability is generally low, with marked differences observed across species, for example, bioavailability rates of 26.5% in CF-1 mice and just 1.6% in Sprague Dawley rats
*Dose↝, plasma concentrations exceeded 1 μM only when doses of 1 g or higher were administered.
*Half-Life↝, Specifically, a dose of 1600 mg yielded a Cmax of 3392 ng/mL (range: 130–3392 ng/mL), with peak levels observed between 1.3 and 2.2 h, AUC (0–∞) values ranging from 442 to 10,368 ng·h/mL, and a half-life (t1/2z) of 1.9 to 4.6 h.
*BioAv↑, Studies on the distribution of EGCG have revealed that, despite its limited absorption, it is rapidly disseminated throughout the body or quickly converted into metabolites
*BBB↑, Additionally, EGCG can cross the blood–brain barrier, allowing it to reach the brain
*hepatoP↓, Several studies have documented liver damage linked to green tea consumption [48,49,50,51,52,53].
*other↓, EGCG has also been shown to inhibit the intestinal absorption of non-heme iron in a dose-dependent manner in a controlled clinical trial
*Inflam↓, EGCG has been widely recognized for its anti-inflammatory effects
*NF-kB↓, EGCG has been shown to suppress NF-κB activation, inhibit its nuclear translocation, and block AP-1 activity
*AP-1↓,
*iNOS↓, downregulation of pro-inflammatory enzymes like iNOS and COX-2 and scavenging of ROS/RNS, including nitric oxide and peroxynitrite
*COX2/PTGS2↓,
*ROS↓,
*RNS↓,
*IL8↓, EGCG has been shown to suppress airway inflammation by reducing IL-8 release, a cytokine involved in neutrophil aggregation and ROS production.
*JAK↓, EGCG blocks the JAK1/2 signaling pathway
*PDGFR-BB↓, downregulate PDGFR and IGF-1R gene expression
*IGF-1R↓,
*MMP2↓, reduce MMP-2 mRNA expression
*P53↓, downregulation of the p53-p21 signaling pathway and the enhanced expression of Nrf2
*NRF2↑,
*TNF-α↓, 25 to 100 μM reduced the levels of TNF-α, IL-6, and ROS while enhancing the expression of E2F2 and superoxide dismutases (SOD1 and SOD2), enzymes vital for cellular antioxidant defense.
*IL6↓,
*E2Fs↑,
*SOD1↑,
*SOD2↑,
Casp3↑, EGCG has been shown to activate key apoptotic pathways, such as caspase-3 activation, cytochrome c release, and PARP cleavage, in various cell models, including PC12 cells exposed to oxidative stress
Cyt‑c↑,
PARP↑,
DNMTs↓, (1) the inhibition of DNA hypermethylation by blocking DNA methyltransferase (DNMT)
Telomerase↓, (2) the repression of telomerase activity;
Hif1a↓, (3) the suppression of angiogenesis via the inhibition of HIF-1α and NF-κB;
MMPs↓, (4) the prevention of cellular metastasis by inhibiting matrix metalloproteinases (MMPs);
BAX↑, (5) the promotion of apoptosis through the activation of pro-apoptotic proteins like BAX and BAK
Bak↑,
Bcl-2↓, while downregulating anti-apoptotic proteins like BCL-2 and BCL-XL;
Bcl-xL↓,
P53↑, (6) the upregulation of tumor suppressor genes such as p53 and PTEN;
PTEN↑,
TumCP↓, (7) the inhibition of inflammation and proliferation via NF-κB suppression;
MAPK↓, (8) anti-proliferative activity through the modulation of MAPK and IGF1R pathways
HGF/c-Met↓, EGCG inhibits hepatocyte growth factor (HGF), which is involved in tumor migration and invasion
TIMP1↑, EGCG has also been shown to influence the expression of tissue inhibitors of metalloproteinases (TIMPs) and MMPs, which are involved in tumorigenesis
HDAC↓, nhibition of UVB-induced DNA hypomethylation and modulation of DNMT and histone deacetylase (HDAC) activities
MMP9↓, inhibiting MMPs such as MMP-2 and MMP-9
uPA↓, EGCG may block urokinase-like plasminogen activator (uPA), a protease involved in cancer progression
GlutMet↓, EGCG can exert antitumor effects by inhibiting glycolytic enzymes, reducing glucose metabolism, and further suppressing cancer-cell growth
ChemoSen↑, EGCG’s combination with standard chemotherapy drugs may enhance their efficacy through additive or synergistic effects, while also mitigating chemotherapy-related side effects
chemoP↑,

3594-

EGCG,

Epigallocatechin-3-gallate inhibits secretion of TNF-alpha, IL-6 and IL-8 through the attenuation of ERK and NF-kappaB in HMC-1 cells

in-vitro,

AD,

HMC1

PMA+A23187-induced (treated as normal cells)

*TNF-α↓, EGCG (100 microM) inhibited PMA+A23187-induced TNF-alpha, IL-6 and IL-8 expression and production.
*IL6↓,
*IL8↓,
*Ca+2↓, EGCG inhibited the intracellular Ca(2+) level.

1976-

EGCG,

Epigallocatechin-3-gallate exhibits anti-tumor effect by perturbing redox homeostasis, modulating the release of pro-inflammatory mediators and decreasing the invasiveness of glioblastoma cells

in-vitro,

GBM,

U87MG

50-100uM

ROS↑, Polyphenol epigallocatechin-3-gallate (EGCG) induced apoptosis in glioma cells by elevating oxidative stress through increased reactive oxygen species (ROS) generation. Signs of apoptosis included altered mitochondrial membrane potential and elevated
MMP↓, altered mitochondrial membrane potential
Casp3↑, elevated expression of caspase-3 (5fold) and cytochrome c
Cyt‑c↑,
Trx1↓, The increase in ROS was concomitant with the decrease in expression of thioredoxin (TRX-1)
Ceru↓, and ceruloplasmin (CP)
IL6↓, EGCG downregulated the levels of pro-inflammatory cytokine interleukin (IL)-6 and chemokines IL-8, monocyte-chemoattractant protein (MCP)-1 and RANTES
IL8↓,
MCP1/CCL2↓,
RANTES?,
uPA↝, 40-50% decrease in uPa activity was observed in glioma cells upon treatment with 50 and 100 uM of EGCG
ROS↑, ROS production, a significant 1.7- and 2-fold (p<0.05) increase in ROS production was observed in cells treated with 50 and 100 uM EGCG respectively,

6356-

Eug,

Cin,

Investigating the Molecular Mechanisms of the Anticancer Effects of Eugenol and Cinnamaldehyde Against Colorectal Cancer (CRC) Cells In Vitro

in-vitro,

CRC,

SW-620

in-vitro,

CRC,

Caco-2

in-vitro,

Nor,

NCM460

P21↑, In CRC cell lines, p21 levels were significantly increased only by EU 600 μM treatment.
ChemoSen↑, CN yielded a stronger anti-inflammatory action. We confirmed that EU and CN are promising natural candidates in CRC prevention and treatment, even in association with chemotherapeutic drugs.
Casp3↑, EU treatment (600 μM) induced an increase in active caspase-3 while in Caco-2 cells
IL4↓, EU and CN, individually and in combination, especially at higher concentrations, effectively reduced the levels of IL-4 and IL-8 in both CRC cell lines
IL8↓,
ROS↑, cytotoxic effects probably through a mitochondria-dependent apoptotic mechanism, which becomes evident mainly at concentrations that induce ROS-mediated cell death
NRF2↑, In Caco-2 cells, where the basal inflammatory tone is low, EU can activate the Nrf2–HO-1 pathway, a redox-regulated cytoprotective system that limits oxidative stress and restrains inflammatory signaling
HO-1↑,
EMT↓, EU predominantly acts by attenuating survival and migration pathways and by reducing EMT-associated transcriptional signatures rather than by directly modulating inflammatory signaling.

6330-

Eug,

Molecular Mechanisms of Action of Eugenol in Cancer: Recent Trends and Advancement

Review,

Var,

TumCD↑, investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule.
TumCCA↑,
AntiCan↑,
Apoptosis↑, The suggested techniques can be enlisted as induction of apoptosis, cell cycle arrest, reducing angiogenesis, interplaying dual roles as an oxidant and pro-oxidant, inhibiting inflammation, and stopping cellular invasion and metastasis.
angioG↓,
TumCI↓,
TumMeta↓,
ChemoSen↑, Combining cisplatin (30 µM) with eugenol (1 µM) potentiated its chemotherapeutic activity by inhibiting aldehyde dehydrogenases (ALDH) enzyme activity, impeding the nuclear factor kappa B (NF-κB) and signaling cascade by reducing binding affinity of
ALDH↓,
NF-kB↓,
IL6↓, downregulating IL-6 and IL-8 mRNA (messenger ribonucleic acid).
IL8↓,
BAX↑, Increased Bcl-2/Bax ratio, elevated levels of proapoptotic protein Bax, increased expression of cleaved caspases-3 and -9, cleaved poly (ADP-ribose) polymerase (PARP) on the higher side
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Bcl-2↓, epression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) accounted for the apoptotic potential for the combination of eugenol and cisplatin.
MMP2↓, repression of the expression level of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) explained the inhibition of the invasive tendency of the TNBCs by combination therapy
MMP9↓,
EMT↓, Reduced epithelial-to-mesenchymal transition (EMT) was evident from reduced expressions of N-cadherin and Snail1 and higher E-cadherin expression.
N-cadherin↓,
Snail↓,
E-cadherin↑,
SOX2↓, Inhibition of pluripotency was evident by reduced expression of biomarker Sox-2 [(sex determining region Y)-box 2]
ROS↑, (MCF-7) (IC50: 22.75 𝜇M) and MDA-MB-231 (IC50: 15.09 𝜇M) breast cancer cells with increasing ROS levels which inhibited cell cycle at G2/M phase, that leads to clastogenesis in vitro.
PCNA↓, downregulated the proliferation of the cell nuclear antigen (PCNA) associated with deceased mitochondria membrane potential (ΔΨm) and upregulation of Bcl-2 associated X protein (Bax)
MMP1↓,
Cyt‑c↑, release of cytochrome-c and lactate dehydrogenase was also observed at a concentration of eugenol of more than 0.9 mM.
LDH↑,
CSCs↓, Downregulation of cancer stem cell markers octamer-binding transcription factor 4 (oct4), Notch1 (Neurogenic locus notch homolog protein 1), epithelial cellular adhesion molecule (EpCAM), and CD44 was observed in the stem cells
OCT4↓,
NOTCH1↓,
EpCAM↓,
CD44↓,
HER2/EBBR2↓, A therapeutic dose (80 μM) of eugenol was shown to cease the proliferating of human epidermal growth factor of receptor 2 (HER-2) positive MCF-10AT cell lines by 32.8%.
VEGF↓, The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), and MMPs are all reduced by eugenol, while that of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) and TIMP-2 is in
TIMP2↑,
eff↑, Eugenol-loaded chitosan nanopolymers (IC50: 7.5 µM) convincingly induce apoptosis and inhibition of metastasis in rat C6 glioma cells.
Ca+2↑, Eugenol (100–300 µM) stimulated PLC-dependent Ca2+ discharge from the endoplasmic reticulum and promoted Ca2+ influx
TumVol↓, Eugenol significantly reduced tumors (nearly 40%) and delayed the time to the endpoint (by 19%) in B16 melanoma xenografts.
DNAdam↑, EUG MCF-7 cells ↑ DNA fragmentation, ↓ intracellular glutathione level, ↑ intracellular H2O2 and lipid peroxidation, ↑ apoptosis 1–4 mM
GSH↓,
H2O2↑,
lipid-P↑,

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

7042-

GA,

Gallic acid reduces cell growth by induction of apoptosis and reduction of IL-8 in HepG2 cells

in-vitro,

Liver,

HepG2

*Inflam↓, Gallic acid is a phenolic acid found in many natural products and have shown anti-inflammatory, anti-tumor, anti-mutagenic and antioxidant actions.
*AntiTum↑,
*antiOx↑,
TumCP↓, Results showed that the gallic acid decreased the proliferation of HepG2 cells in a dose-dependent manner (Trypan blue exclusion assay), without causing necrosis (LDH assay).
IL8↓, We observed a significant reduction in the levels of IL-8 and increased levels of IL-10 and IL-12 (
IL10↑,
IL12↑,
Apoptosis↑, Gallic acid induces HepG2 cells apoptosis

6573-

Ger,

Systematic elucidation of the mechanism of geraniol via network pharmacology

Study,

Nor,

Study,

Var,

HO-1↝,
HRAS↓,
*IL8↓,
*AChE↓,
NF-kB↓,
PCNA↓,
BAX↑,
Bcl-2↓,
P53↑,
Casp3↑,
Casp8↑,
Casp9↑,

7927-

H2,

Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients

Human,

Asthma,

In total, 2.4% hydrogen containing steam mixed gas (XEN) was inhaled once for 45 min in 10 patients with asthma and 10 patients with COPD.

*IL8↓, decreased IL-8 level only in asthma group
*IL4↓, IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80–0.64 pg/mL, P = 0.025) and asthma (0.06–0.05 pg/mL, P = 0.007) group, respectively.
*IL6↓,
*Inflam↓, A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD
*Sepsis↓, has been demonstrated that hydrogen could provide protection against various diseases, including sepsis, stroke and ischemia-reperfusion injury
*Stroke↓,
*antiOx↑, Hydrogen, which exhibits anti-oxidative and anti-inflammation effects, was proved to be relatively safe for inhalation in diving.9
*toxicity↓,

2514-

H2,

Hydrogen: A Novel Option in Human Disease Treatment

Review,

NA,

*Inflam↓, Anti-Inflammatory Effect of H2
*IL1β↓, decrease the overexpression of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α
*IL6↓,
*IL8↓,
*IL10↓,
*TNF-α↓,
*ROS↓, . H2 can also downregulate ROS directly or as a regulator of a gas-mediated signal.
*HO-1↓, H2 can enhance the expression of the heme oxygenase-1 (HO-1) antioxidant by activating nuclear factor erythroid 2-related factor 2 (Nrf-2), an upstream regulating molecule of HO-1
*NRF2↑,
*ER Stress↓, hydrogen inhalation significantly reduced the ER stress-related protein and alleviated tissue damage in myocardial I/R injury a
H2O2↑, H2-induced ROS production can also be observed in cancer cells.

7539-

HT,

Polyphenols Extracts from Oil Production Waste Products (OPWPs) Reduce Cell Viability and Exert Anti-Inflammatory Activity via PPARγ Induction in Colorectal Cancer Cells

in-vitro,

CRC,

HCT116

HCT116 cells at 0, 25, 50, 100, 150, 200 and 300 µM for 72 h

in-vitro,

CRC,

LoVo

tumCV↓, Hydroxytyrosol (HTyr), the major constituent of these extracts, was used as the control. We show that both HTyr and the extracts affect cell viability by inducing apoptosis and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
p‑NF-kB↑, downregulate inflammation by impairing NF-κB phosphorylation and expression of responsive cytokine genes, as TNF-α and IL-8, at both mRNA and protein levels
TNF-α↑,
IL8↓,
PPARγ↑, Mechanistically, HTyr and the extracts activate PPARγ while hampering pro-inflammatory genes expression
Inflam↓,
Dose↝, extraction procedure for OPWPs that makes use of membrane technologies, micro-, nano- and ultrafiltration along with reverse osmosis as purification steps.

7567-

HYP,

Hyperoside: A review on its sources, biological activities, and molecular mechanisms

Review,

Var,

*AntiCan↑, anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects.
*Bacteria↓,
*AntiViral↑,
*antiD↓,
*RenoP↑, Kidney protection
*hepatoP↑, Liver protection
*eff↑, treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers.
*Sepsis↓,
*AntiArt↑,
*Stroke↓,
TumCMig↓, hyperoside has been shown to inhibit the migration and invasion properties of A549 cells by suppressing the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase-2 inhibitor (TIMP-2), matrix metalloproteinase (MMP)-2
TumCI↓,
MTA1↓,
TIMP2↓,
MMP2↓,
MMP↓, disrupted the penetration of the mitochondrial membrane, and triggered mitochondrial cytochrome C and apoptosis inducers into the cytoplasm
Cyt‑c↑,
Akt↓, inhibited the Akt/mTOR/p70S6K signaling pathway in NSCLC cells to promote autophagy and exerted anticancer activity
mTOR↓,
P70S6K↓,
TumAuto↑,
PD-L1↓, thereby inhibiting PD-L1 expression at the transcriptional leve
TNF-α↓, subsequently, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1b, IL-6 and IL-8, were significantly down-regulated
IL1β↓,
IL6↓,
IL8↓,
Bcl-2↓, Hyperoside was reported to inhibit the over-expression of B-cell lymphoma factor 2 (Bcl)-2 and Bcl-x in lung cancer cells, and up-regulate the preapoptotic factors such as Bax, Bad, and Bak.
Bcl-xL↓,
BAX↑,
BAD↑,
Bak↑,
VEGF↓, decreasing the HeLa cell's vascular endothelial growth factor (VEGF) expression levels in HeLa cells.
Casp3↑, hyperoside promoted apoptosis via enhancing caspase-3 and caspase-8 protein expression, and on the other hand, by promoting tumor suppressor gene P35 expression
Casp8↑,
P53↑,
GSH↓, Hyperoside could also reduce glutathione levels in HeLa cells, superoxide dismutase (SOD), and Catalase (CAT) viability.
SOD↓,
Catalase↓,
TAC↓, reduced the antioxidant capacity and thus to inhibit cancer cell growth
XIAP↓, MCF-7 and 4 T1 cells Decreased the levels of Bcl-2 and XIAP; increased the levels of Bax and cleaved cysteine protease-3; decreased the production of ROS and inhibited NFκB signal pathway
ROS↓,
NF-kB↓,
TLR4↓, MDA-MB-231 cells Inhibited TLR4-NF-κB signaling pathways; decreased the expression of Bcl-2; enhanced the expression of pro-apoptotic Bax and the level of pro-inflammatory cytokine IL-6
P-gp/ABCB1↓, S180 cancer cell Reduced the expression of P-gp, LRP and Bcl-2 and increased the expression of Fas; inhibited bad phosphorylation and increased p27 level
LRP1↓,
Fas↑,
p27/CDKN1B↑,
*cardioP↑, Cardiovascular protection In vivo pulmonary embolism and arterial thrombosis model Prolonged the activated prothrombin time and suppressed thrombin and FXa activities; inhibit the production of PAI-1 induced by TNF-α
*AntiThr↑,
*PAI-1/SERPINE1↓,
*BUN↓, Reduced the contents of serum angiotensin converting enzyme ArgII, ALD, U-mAlb, BUN, SCR, ALT, and AST
*ALAT↓,
*AST↓,
*neuroP?, Neuroprotection

7565-

HYP,

Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review

Review,

AD,

*Inflam↓, exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects,
*antiOx↑,
*neuroP↑,
*lipid-P↓, Anti-oxidant Saccharomyces Cerevisiae 5, 20 mg/L Decreased LPO and the level of ROS
*ROS↓,
*IL1β↓, HT22 cells 20 μM Alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF.
*IL6↓,
*IL8↓,
*TNF-α↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Catalase↑,
*SOD↑,
*GSH↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*BDNF↑, Male Albino Swiss mice 0.94 mg/kg, 3.75 mg/kg Mediated by monoaminergic system and the upregulation of BDNF level
*NF-kB↓, Inhibited the activation of NF-κB, lessened the expression of iNOS,
*AChE↓, ICR mice 2.5 mg/kg Inhibited AchE activity
*H2S↑, SD rats 1, 10, 100 μM Upregulation of H2S,
Casp3↑, Anti-lung cancer A549 cells, Balb/c-nude mice 15, 20, 25 μM in vitro 15, 20, 25 mg/kg in vivo Activation of caspase-3 to motivate apoptosis and inactivation of NF-κB to inhibit inflammatory
Apoptosis↑,
NF-kB↓,
AMPK↑, A549 cells 10, 50, 100 μM Upregulation of AMPK signal pathway and HO-1 expression to suppressed the survival and proliferation of A549 cells
HO-1↑,
MAPK↑, A549 cells, H466 cells, C57BL/6J mice – Upregulated the expression of p38 MAPK, caspase 3, caspase 9, cleaved caspase 3, cleaved caspase 9 and Bax, downregulated the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1 and Bcl-2
cl‑Casp3↑,
cl‑Casp9↑,
BAX↑,
SOD?,
Catalase↓,
NRF2↓,
NQO1↓,
HO-1↓,
Bcl-2↓,
TumCCA↑, A549 cells 10, 20, 50, 100, 200, 400 μg/mL Inhibited the process of G1/S phase to inhibit proliferation
FOXO1↑, NCI-H1975 cells, PC-9 cells, Nude male mice 30, 60, 90, 120, 150 μM in vitro, 25 mg/kg in vivo Upregulation of FoxO1
TumAuto↑, A549 cells 0.5, 1, 2 mM Induced autophagy through inhibiting the Akt/mTOR/p70S6K signal pathway
Akt↓,
mTOR↓,
P70S6K↓,
BMP7/OP1↓, HepG2 cells 5, 10, 20, 40, 80 μM Inhibiting the BMP-7
*cardioP↑, Cardiovascular Protective Effect
*hepatoP↑, Hepatoprotective
*antiCG↑, The report indicates hyperoside possesses antithrombotic activities and offer bases for development of a novel anticoagulant
*AntiThr↑,
*Diar↓, Antidiarrheal Activity
*AntiFungal↑, Antifungal Activity
*CYP2D6↓, hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and might cause herb-drug interactions when co-administrated with CYP2D substrates.
*PDGFR-BB↓, In diabetic rats’ model, hyperoside inhibited the platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor-B receptor (PDGFR-β) ligand binding
*PDGFRB↓,
*toxicity↓, In research conducted in Wistar rats, the researchers demonstrated that in a long-term oral administration lasted for 6 months, hyperoside has a good safety. And the possible target organ of toxicity is kidney and the damage is reversible
*Half-Life↑, hyperoside also showed a long half-life for 4 hours and the safety experiments also proves that it has good safety.

7560-

HYP,

Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity

Review,

Nor,

Review,

AD,

*RenoP↓, Thirdly, long-term use of hyperoside is toxic to the kidneys, but the damage is reversible
Casp3↑, Up-regulates caspase-3, caspase-8, Bax, p53 and MDA contents; decreases GSH, SOD and CAT activities; decreases VEGF and Bcl-2 levels; and inhibits cell growth. HeLa 100 μmol/L
Casp8↑,
MDA↑,
GSH↓,
SOD↓,
Catalase↓,
VEGF↓,
Bcl-2↓,
TumCG↓,
p‑Akt↓, Down-regulates BMP-7 expression, AKT phosphorylation and PI3K expression; induces cell cycle arrest; and inhibits cell proliferation. Human HepG2 5, 10, 20, 40 and 80 μM
PI3K↓,
TumCCA↑,
TumCP↓,
BMP7/OP1↓,
*ZO-1↑, up-regulates ZO-1 and claudin5 protein expression; maintains the integrity of the blood–brain barrier; and may protect neural function in CIR-injured mice. CIR injury induced by MCAO in mice 50 mg/kg
*BBB↝,
*p‑Akt↑, increases the phosphorylation of AKT and GSK-3β; alleviates early brain injury after subarachnoid haemorrhage; and promotes nerve function recovery in rats.
*GSK‐3β↑,
*SOD↑, increases SOD and CAT activities and GSH content; increases SIRT1 gene expression; down-regulates NF-κB mRNA
*Catalase↑,
*GSH↑,
*SIRT1↑,
*NF-kB↓,
*IL1β↓, Down-regulates IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax and caspase-3 levels; increases CAT, SOD and GSH activities; up-regulates Bcl-2, BDNF, TrkB, SIRT1 and NGF expression; reduces LPS-induced inflammation, oxidative stress and apoptosis; and protec
*IL6↓,
*IL8↓,
*TNF-α↓,
*ROS↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*Apoptosis↓,
*cardioP↑, Cardioprotective Activity of Hyperoside.
*AST↓, Decreases the levels of AST, CK, CK-MB and c-TnT in rats; the rate of cardiomyocyte apoptosis;
*hepatoP↑, Hepatoprotective Activity of Hyperoside.
*AST↓, Decreases liver index, AST, ALT, MDA and Bach1 complex levels and alleviates the pathological damage of acute liver injury mice.
*ALAT↓,
*MDA↓,
*BACH1↓,
*neuroP↑, Brain-Protective Activity of Hyperoside.
*Stroke↓, Down-regulates TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, TLR4, COX-2, NF-κB, caspase-3, caspase-9, Bax and Bcl-2 expression and prevents CIR injury. Middle cerebral artery occlusion/reperfusion rat model
*ICAM-1↓,
*VCAM-1↓,
*TLR4↓,
*COX2/PTGS2↓,
*RenoP↑, Renal-Protective Activity of Hyperoside.
*NLRP3↓, Suppresses NLRP3, caspase-1 and ASC expression and prevents acute kidney injury induced by lipopolysaccharide. Mouse acute kidney injury model
*Casp1↓,
*ASC↓,
*BioAv↓, low oral bioavailability
*BioAv↑, hyperoside is compatible with other traditional Chinese medicines and they can improve its bioavailability and oral absorption.
*toxicity↓, Firstly, an acute toxicity test of hyperoside showed that its LD50 > 5000 mg/kg

7592-

I3C,

Indole-3-carbinol as a chemopreventive and anti-cancer agent

Review,

Var,

JNK↑, indole-3-carbinol has been shown to activate the stress-induced MAP kinases p38 and c-jun N-terminal kinase (JNK) in prostate cancer cells (66), and to inhibit constitutively active STAT3,
STAT3↓,
TumCCA↑, Indole-3-carbinol and DIM exhibit the ability to cause G1 arrest in breast and prostate cancer cells
P21↑, upregulation of the CDK inhibitors p21WAF1 and p27kip1, and the concurrent downregulation of cyclin D1, cyclin E, and CDKs 2, 4, and 6,
p27/CDKN1B↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
AhR↑, indole-3-carbinol has been reported to increase AhR expression in MCF-7 cells
ER-α36↓, Indole-3-carbinol is a negative regulator of ERα signaling in human tumor cells
ChemoSen↑, Consequently, indole-3-carbinol could cooperate with tamoxifen to inhibit breast cancer proliferation
ER Stress↑, indole-3-carbinol and DIM induced endoplasmic reticulum stress responses in cancer cells via unfolded protein response pathways,
UPR↑,
BRCA1↑, indole-3-carbinol/DIM-induced endoplasmic reticulum stress and upregulation of the expression of the tumor suppressor genes BRCA1 and BRCA2 in prostate and breast cancer cells
BRCA2↑,
TumCMig↓, Indole-3-carbinol has been reported to inhibit the migration and invasion of breast cancer cells
TumCI↓,
VEGF↓, decreased vascular endothelial growth factor (VEGF), increased interleukin-8 (IL-8) secretion, and decreased activities of MMP-2 and MMP-9
IL8↓,
MMP2↓,
MMP9↓,
RadioS↑, Chemo- and radiosensitizing effects of indole-3-carbinol/DIM
Akt↓, Inhibition of Akt/NF-κB signaling
NF-kB↓,
DR4↑, Induction of death receptor (DR)4 and DR5 expression
DR5↑,

7702-

IP6,

Ins,

capec,

Inositol Hexakisphosphate and Inositol Enhance the Inhibition of Colorectal Cancer Growth and Liver Metastasis by Capecitabine in a Mouse Model

in-vivo,

CRC,

 xenograft mouse model.

Dose↝, capecitabine (60 mg/kg) treatment group, an IP6 + INS (80 mg/kg: 80 mg/kg) treatment group, and a capecitabine + IP6 + INS (60 mg/kg: 80 mg/kg: 80 mg/kg) treatment group.
AntiTum↑, Compared with the model group, the tumor parameters of the other three treatment groups were significantly reduced.
OS↑, The combination of IP6 and INS with capecitabine is more effective in improving survival rate, reducing tumor weight, and inhibiting liver metastasis.
TumW↓,
TumMeta↓,
E-cadherin↑, expression of E-cadherin in each treatment group was elevated, while the expression of N-cadherin and vimentin was suppressed.
N-cadherin↓,
Vim↓,
TNF-α↓, combination more significantly reduced the expression levels of TNF-α, IL-6, and IL-8 in the serum of CRC mice compared with other intervention groups
IL6↓,
IL8↓,
ChemoSen↑, Our data indicate that IP6 and INS enhanced the effect of capecitabine on CRC growth in mice by modulating the expression of inflammatory factors, intercellular adhesion molecules, and vimentin.

7760-

ISL,

Pharmacological Potentials and Delivery Strategies of Isoliquiritigenin: Challenges and Advances in Enhancing Bioavailability

Review,

Nor,

*BioAv↓, Although ISLT has been globally recognized for its health benefits, its oral administration is still restricted by sparing water solubility, poor bioavailability, and slow dissolution in the intestine.
GlucoseCon↓, ISLT (MGC803 cells: 40 μM, SGC7901 cells: 50 µM) downregulated the expression of glucose transporter four and reduced the uptake of glucose by GC cells.
LDH↓, demonstrated that it suppressed the activity of lactate dehydrogenase and pyruvate dehydrogenase kinase 1 and reduced the production of glycolytic products.
PDK1↓,
Glycolysis↓,
mt-OXPHOS↓, It impaired mitochondrial function while simultaneously suppressing glycolysis and inhibiting mitochondrial oxidative phosphorylation, ultimately leading to energy metabolic collapse in GC cells.
Bax:Bcl2↓, it decreased the Bcl-2/Bax ratio and upregulated cleaved caspase-3/caspase-9 to promote GC cell apoptosis.
cl‑Casp3↑,
cl‑Casp9↑,
Apoptosis↑,
Hif1a↓, hypoxia-inducible factor-1α was downregulated to regulate the energy metabolism and proliferative activity of GC cells
ROS↑, ISLT-17 increases the production of Reactive oxygen species (ROS) in GC cells, thereby inhibiting cell growth.
*AntiDiabetic↑, ISLT possesses therapeutic effects on various diseases such as diabetes, cardiovascular diseases, and kidney diseases by activating the Nrf2 pathway
*cardioP↑,
*RenoP↑, structure in patients with diabetic kidney disease, inhibited oxidative stress and reduced ROS levels, and suppressed the activation of NF-kappa B and NLRP3 inflammasomes and the occurrence of pyroptosis, which played a renal protective role
*ROS↓,
*NF-kB↓,
*NLRP3↓,
*Pyro↓,
*antiPs↑, ISLT (1 mg/kg/day and 2 mg/kg/day) ameliorates psoriasis by inhibiting IL-6 and IL-8 and inhibiting inhibitory nuclear factor-kappa B activity, resulting in a reduction in pro-inflammatory.
*IL6↓,
*IL8↓,
BioAv↑, Compared with traditional oral and injectable methods, transdermal administration possesses significant advantages, such as protection against first-pass effects, improved bioavailability, enhanced patient compliance, prolonged drug stability, and th
BioAv↑, Accordingly, transdermal drug delivery systems containing intercellular lipid components (ceramides) can effectively improve the transdermal efficiency of lipophilic drugs, including ISLT.
BioAv↑, ISLT@NPs possessed significantly higher targeted accumulation in the colon and improved tissue penetration than free DiR, suggesting higher oral bioavailability.

7917-

IVT,

A review on the pharmacological effects of vitexin and isovitexin

Review,

Nor,

Review,

AD,

*antiOx↑, anti-oxidant, anti-cancer, anti-inflammatory, anti-hyperalgesic, and neuroprotective effects.
*AntiCan↑,
*Inflam↓,
*neuroP↑,
*AChE↓, Anti-Alzheimer's disease Vitexin/isovitexin In vitro ChE enzyme assay Vitexin: IC 50 = 12.16 ± 3.58 (AChE) IC 50 = 6.73 ± 0.08 (BChE) IC 50 = 51.07 ± 3.31(BACE1) Isovitexin: IC 50 = 6.24 ± 1.15 (AChE) IC 50 = 6.48 ± 0.43 (BChE) IC 50 ≥ 100 (BA
*BChE↓,
*BACE/β-secretase↓,
*Stroke↓, Data showed that vitexin exhibits protective effect against cardiac ischemia/reperfusion (I/R) injury through inhibiting the I/R-induced decrease in coronary flow
*AntiAg↓, Vitexin-containing lime leaf significantly inhibited platelet aggregation in a concentration-dependent manner
*AntiDiabetic↑, Administered orally, vitexin and isovitexin significantly reduced postprandial blood glucose both in sucrose loaded normoglycemic mice and sucrose induced diabetic rat
*AGEs↓, vitexin and isovitexin, as AGE inhibitors,
*IL1β↓, inhibition in the pro-inflammatory cytokines such as IL-1β, IL6, IL-8, TNF-α,
*IL6↓,
*IL8↓,
*TNF-α↓,
*Obesity↓, Protective effects against obesity
*BioAv↝, Unusually, vitexin and isovitexin are poorly absorbed in the gastrointestinal tract [61]. They directly reached the colon where they were hydrolysed by the gut microflora through deglycosylation and ringopening of the heterocyclic C ring
*BioAv↓, oral bioavailability of vitexin was much low (approximately 5%

4292-

LT,

Luteolin for neurodegenerative diseases: a review

Review,

AD,

Review,

Park,

Review,

MS,

Review,

Stroke,

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

Showing Research Papers: 1 to 50 of 81
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 81

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1, antiCG↑, 1, antiD↓, 1, CYP2D6↓, 1, Stroke↓, 4,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 12, ARE↑, 1, Bil↑, 1, Catalase↑, 4, Fenton↓, 1, GCLC↑, 1, GCLM↑, 1, GPx↑, 1, GSH↑, 4, GSR↑, 1, GSTs↑, 2, HO-1↓, 1, HO-1↑, 5, Keap1↓, 1, lipid-P↓, 6, MDA↓, 9, MPO↓, 1, NQO1↑, 1, NRF2↑, 7, RNS↓, 2, ROS↓, 18, SOD↑, 10, SOD1↑, 1, SOD2↑, 1, TBARS↓, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 3, AMPK↑, 2, BUN↓, 1, CREB↑, 1, glucose↓, 1, GlucoseCon↑, 1, GLUT2↑, 1, H2S↑, 2, LDH↓, 2, PPARγ↑, 2, p‑PPARγ↓, 1, SIRT1↑, 1,

Cell Death(tgid=5) ⓘ

Akt↓, 1, p‑Akt↑, 1, Apoptosis↓, 1, BAX↓, 2, Bax:Bcl2↓, 1, Bcl-2↑, 2, Casp1↓, 1, Casp3↓, 3, Casp9↑, 1, iNOS↓, 5, JNK↓, 1, MAPK↓, 2, p‑MAPK↓, 1, p38↓, 1, Pyro↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 2, other↓, 1, other↑, 1, other↝, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↓, 1, GRP78/BiP↑, 1, UPR↑, 1,

DNA Damage & Repair(tgid=10) ⓘ

P53↓, 1,

Cell Cycle & Senescence(tgid=11) ⓘ

E2Fs↑, 1,

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

ERK↓, 1, GSK‐3β↓, 2, GSK‐3β↑, 1, IGF-1R↓, 1, PDGFRB↓, 1, PI3K↓, 1, STAT↓, 1,

Migration(tgid=13) ⓘ

5LO↓, 1, AntiAg↓, 1, AP-1↓, 1, BACH1↓, 1, Ca+2↓, 2, E-sel↓, 1, MMP2↓, 2, MMP3↓, 1, MMP9↓, 1, PAI-1/SERPINE1↓, 1, VCAM-1↓, 3, ZO-1↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 5, PDGFR-BB↓, 2,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 4, BBB↝, 1, GLUT3↑, 1, GLUT4↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

ASC↓, 1, COX2/PTGS2↓, 10, CRP↓, 1, CXCR4↓, 1, ICAM-1↓, 3, IFN-γ↓, 3, IKKα↓, 1, IL1↓, 2, IL10↓, 1, IL10↑, 3, IL12↓, 3, IL17↓, 2, IL18↓, 1, IL1β↓, 12, IL2↓, 2, IL2↑, 1, IL33↓, 1, IL4↓, 1, IL6↓, 19, IL8↓, 24, Inflam↓, 17, JAK↓, 2, LTA/TNF-β↑, 1, MCP1/CCL2↓, 1, NF-kB↓, 14, PGE2↓, 5, TLR4↓, 2, TNF-α↓, 19, TNF-α↑, 1, TRAF1↓, 1,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 4, BChE↓, 1, BDNF↑, 5, ChAT↑, 1, NGF↑, 2, tau↓, 3, TrkB↑, 3,

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1, Aβ↓, 2, BACE/β-secretase↓, 2, NLRP3↓, 4, XO↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 9, BioAv↑, 6, BioAv↝, 4, Dose↑, 1, Dose↝, 3, eff↑, 6, Half-Life↑, 1, Half-Life↝, 5, selectivity↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 3, AST↓, 4, Bil↑, 1, BloodF↑, 1, BMD↑, 2, BP↓, 1, creat↓, 1, CRP↓, 1, GutMicro↑, 3, IL6↓, 19, LDH↓, 2,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3, AntiDiabetic↓, 1, AntiDiabetic↑, 3, antiPs↑, 1, AntiTum↑, 1, cardioP↑, 9, chemoPv↑, 1, cognitive↑, 4, cognitive↝, 1, hepatoP↓, 1, hepatoP↑, 6, memory↑, 5, neuroP?, 1, neuroP↑, 10, Obesity↓, 1, radioP↑, 1, RenoP↓, 1, RenoP↑, 4, toxicity↓, 4,

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 1, Diar↓, 1, Sepsis↓, 2,
Total Targets: 179

Scientific Paper Hit Count for: IL8, Interleukin-8

6 Curcumin
4 Quercetin
3 Crocetin
3 EGCG (Epigallocatechin Gallate)
3 Hyperoside
3 Lycopene
3 Sulforaphane (mainly Broccoli)
3 Silymarin (Milk Thistle) silibinin
2 Allicin (mainly Garlic)
2 Artemisinin
2 Ashwagandha(Withaferin A)
2 Eugenol
2 Hydrogen Gas
2 Luteolin
2 Magnetic Fields
2 Propolis -bee glue
2 Resveratrol
2 Rosmarinic acid
2 Rutin
1 Alpha-Lipoic-Acid
1 Andrographis
1 Apigenin (mainly Parsley)
1 Astaxanthin
1 Atorvastatin
1 Berberine
1 Betulinic acid
1 Boron
1 α-Bisabolol / Chamomile oil
1 Butyrate
1 Chocolate
1 Carvone
1 Deguelin
1 Dihydrocaffeic Acid
1 Ellagic acid
1 Echinacea
1 Cinnamon
1 Ferulic acid
1 Gallic acid
1 Geraniol
1 HydroxyTyrosol
1 Indole-3-carbinol
1 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
1 Inositol
1 capecitabine
1 Isoliquiritigenin
1 Isovitexin
1 Melatonin
1 Oleuropein
1 Piperlongumine
1 Pterostilbene
1 Perilla
1 Shikonin
1 Thymoquinone
1 Vitamin C (Ascorbic Acid)

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#:368  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

IL8 Cancer Research Results

Pathway results for Effect on Cancer / Diseased 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) ⓘ

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) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

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) ⓘ

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) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Home Page