SIRT1 Cancer Research Results

SIRT1, Sirtuin 1 protein: Click to Expand ⟱

Source:

Type:

SIRT1 (Sirtuin 1) is a protein that plays a crucial role in various cellular processes, including metabolism, stress resistance, and longevity. In the context of cancer, SIRT1 has been found to have both tumor-suppressing and tumor-promoting functions, depending on the type of cancer and the cellular context.
Expression Promotes: Breast, Prostate, Colorectal Cancer.
Expression Suppresses: Leukemia, Liver Cancers.
-aging process is associated with the inactivation of the silent information regulator T1 (SIRT1) protein.

Scientific Papers found: Click to Expand⟱

400-

AgNPs,

MF,

Polyvinyl Alcohol Capped Silver Nanostructures for Fortified Apoptotic Potential Against Human Laryngeal Carcinoma Cells Hep-2 Using Extremely-Low Frequency Electromagnetic Field

in-vitro,

Laryn,

HEp2

50mT/30mins

3.29 0.4 mol/mL

6x improvement when LEMF added (50mT/15mins)

TumCP↓, especially in the G0/G1 and S phases.
Casp3↑,
P53↑,
Beclin-1↑,
TumAuto↑,
GSR↑, oxidative stress biomarker
ROS↑, oxidative stress biomarker
MDA↑, oxidative stress biomarker
ROS↑,
SIRT1↑,
Ca+2↑, induce apoptosis in osteoclasts by increasing intracellular and nucleus Ca2+ concentration
Endon↑, increases endonuclease activity
DNAdam↑,
Apoptosis↑,
NF-kB↓,

2206-

AgNPs,

RES,

ENHANCED EFFICACY OF RESVERATROL-LOADED SILVER NANOPARTICLE IN ATTENUATING SEPSIS-INDUCED ACUTE LIVER INJURY: MODULATION OF INFLAMMATION, OXIDATIVE STRESS, AND SIRT1 ACTIVATION

in-vivo,

Nor,

Rats

*hepatoP↑, AgNPs + RV treatment significantly reduced pro-inflammatory cytokines, NF-κB activation, presepsin, PCT, 8-OHDG, and VEGF levels compared with the CLP group, indicating attenuation of sepsis-induced liver injury.
*Inflam↓,
*NF-kB↓,
*VEGF↓,
*SIRT1↑, Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects.
*ROS↓, alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation.
*Dose↝, 30 mg/kg of AgNPs + RV was given intraperitoneally to the rats
*Catalase↑, AgNPs + RV treatment exhibited a robust effect in bolstering CAT activity
*MDA↓, AgNPs + RV treatment effectively ameliorates sepsis-induced oxidative stress and inflammation in rat livers by reducing MDA, MPO, and NO levels
*MPO↓,
*NO↓,
*ALAT↓, AgNPs + RV effectively reduced the ALT and AST levels, returning them to values similar to those observed in the Sham group
*AST↓,
*antiOx↑, corroborates the antioxidant potential of RV and AgNPs observed in earlier studies

2646-

AL,

Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress

in-vitro,

Pca,

DU145

in-vitro,

Melanoma,

RPMI-8226

AntiCan↑, simple homemade ethanol-based garlic extract (GE). We show that GE inhibits growth of several different cancer cells in vitro
eff↓, These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile.
ChemoSen↑, We found that GE enhanced the activities of chemotherapeutics
ER Stress↑, Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER) stress.
tumCV↓, homemade GE was found to reduce the viability of the two multiple myeloma (MM) cell lines, RPMI-8226 and JJN3, as well as the prostate cancer cell line DU145 in a dose-dependent manner,
DNAdam↑, GE alone slightly increased the percentage of tail DNA (% Tail) (representing cumulative levels of abasic sites, as well as single- and double-strand DNA breaks) measured at day one, compared to untreated cells
GSH∅, We could not detect any changes in cellular GSH levels after treatments with GE
HSP70/HSPA5↓, ; however, in support of increased ER stress after GE treatment, we detected an increased pulldown of HSPA5 (BIP), a member of the Hsp70 family
UPR↑, s leading to the accumulation of unfolded proteins in the ER (also known as GRP78)
β-catenin/ZEB1↓, we also found a reduction in the β-catenin leve
ROS↑, In further support for increased ER stress induced by GE, which will lead to elevated ROS-levels and oxidative stress
HO-2↑, we found a significant increase in proteins activated by and important for regulating cellular ROS levels, e.g., OXR1, Txnl1, Hmox2, and Sirt1
SIRT1↑,
GlucoseCon∅, glucose consumption, as well as lactate secretion, were not changed.
lactateProd∅,
chemoP↑, Garlic is reported to reduce cisplatin-induced nephrotoxicity and oxidative stress

3433-

ALA,

Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals

*ROS↓, However, in more mature hPSC‐derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis.
*Apoptosis↓,
*Hif1a↑, up‐regulating HIF1A in response to a hypoxic environment.
*FOXO1↑, ALA also up‐regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation
*FOXO3↑,
*ATM↑,
*SIRT1↑,
*SIRT3↑,
*CD34↑, Flow cytometry analysis indicated that ALA improved the production of CD34+ CD43+ CD45+ hematopoietic stem/progenitor cells significantly

3550-

ALA,

Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?

Review,

AD,

*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*PGE2↓, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6
*COX2↓,
*iNOS↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*BioAv↓, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic
*Ach↑, α-LA increases the production of acetylcholine [30], inhibits the production of free radicals [31], and promotes the downregulation of inflammatory processes
*ROS↓,
*cognitive↑, Studies have shown that patients with mild AD who were treated with α-LA showed a slower progression of cognitive impairment
*neuroP↑, α-LA is classified as an ideal neuroprotective antioxidant because of its ability to cross the blood-brain barrier and its uniform uptake profile throughout the central and peripheral nervous systems
*BBB↑,
*Half-Life↓, α-LA presented a mean time to reach the maximum plasma concentration (tmax) of 15 minutes and a mean plasma half-life (t1/2) of 14 minutes
*BioAv↑, LA consumption is recommended 30 minutes before or 2 hours after food intake
*Casp3↓, α-LA had an effect on caspases-3 and -9, reducing the activity of these apoptosis-promoting molecules to basal levels
*Casp9↓,
*ChAT↑, α-LA increased the expression of M2 muscarinic receptors in the hippocampus and M1 and M2 in the amygdala, in addition to ChaT expression in both regions.
*cognitive↑, α-LA acts on these apoptotic signalling pathways, leading to improved cognitive function and attenuation of neurodegeneration.
*eff↑, Based on their results, the authors suggest that treatment with α-LA would be a successful neuroprotective option in AD, at least as an adjuvant to standard treatment with acetylcholinesterase inhibitors.
*cAMP↑, The increase of cAMP caused by α-LA inhibits the release of proinflammatory cytokines, such as IL-2, IFN-γ, and TNF-α.
*IL2↓,
*INF-γ↓,
*TNF-α↓,
*SIRT1↑, Protein expression encoded by SIRT1 showed higher levels after α-LA treatment, especially in liver cells.
*SOD↑, antioxidant enzymes (SOD and GSH-Px) and malondialdehyde (MDA) were analysed by ELISA after 24 h of MCAO, which showed that the enzymatic activities were recovered and MDA was reduced in the α-LA-treated groups i
*GPx↑,
*MDA↓,
*NRF2↑, The ratio of nucleus/cytoplasmic Nrf2 was higher in the α-LA group 40 mg/kg, indicating that the activation of this factor also occurred in a dose-dependent manner

1093-

And,

Andrographolide attenuates epithelial‐mesenchymal transition induced by TGF‐β1 in alveolar epithelial cells

in-vitro,

Lung,

A549

TGF-β↓,
TumCMig↓,
MMP2↓,
MMP9↓,
ECM/TCF↓,
p‑SMAD2↓,
p‑SMAD3↓,
SMAD4↓,
p‑ERK↓,
ROS↓, reduced (TGF‐β1‐induced) intracellular ROS generation
NOX4↓,
SOD2↑,
SIRT1↑, Andro protects AECs from EMT partially by activating Sirt1/FOXO3‐mediated anti‐oxidative stress pathway
FOXO3↑,

3396-

ART/DHA,

Progress on the study of the anticancer effects of artesunate

Review,

Var,

TumCP↓, reported inhibitory effects on cancer cell proliferation, invasion and migration.
TumCI↓,
TumCMig↓,
Apoptosis↑, ART has been reported to induce apoptosis, differentiation and autophagy in colorectal cancer cells by impairing angiogenesis
Diff↑,
TumAuto↑,
angioG↓,
TumCCA↑, inducing cell cycle arrest (11), upregulating ROS levels, regulating signal transduction [for example, activating the AMPK-mTOR-Unc-51-like autophagy activating kinase (ULK1) pathway in human bladder cancer cells]
ROS↑,
AMPK↑,
mTOR↑,
ChemoSen↑, ART has been shown to restore the sensitivity of a number of cancer types to chemotherapeutic drugs by modulating various signaling pathways
Tf↑, ART could upregulate the mRNA levels of transferrin receptor (a positive regulator of ferroptosis), thus inducing apoptosis and ferroptosis in A549 non-small cell lung cancer (NSCLC) cells.
Ferroptosis↑,
Ferritin↓, ferritin degradation, lipid peroxidation and ferroptosis
lipid-P↑,
CDK1↑, Cyclin-dependent kinase 1, 2, 4 and 6
CDK2↑,
CDK4↑,
CDK6↑,
SIRT1↑, Sirt1 levels
COX2↓,
IL1β↓, IL-1? ?
survivin↓, ART can selectively downregulate the expression of survivin and induce the DNA damage response in glial cells to increase cell apoptosis and cell cycle arrest, resulting in increased sensitivity to radiotherapy
DNAdam↑,
RadioS↑,

2292-

Ba,

BA,

Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives

Review,

Var,

AntiCan↑, Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells.
*toxicity↓,
BioAv↝, Baicalein permeates easily through the epithelium from the gut lumen to the blood underneath due to its low molecular mass and high lipophilicity, albeit a low presence of its transporters.
BioAv↓, In contrast, baicalin has limited permeability partly due to its larger molecular mass and higher hydrophilicity [24]. The overall low water solubility of baicalin and baicalein contributes to their poor bioavailability.
*ROS↓, baicalin protected macrophages against mycoplasma gallisepticum (MG)-induced ROS production and NLRP3 inflammasome activation by upregulating autophagy and TLR2-NFκB pathway
*TLR2↓,
*NF-kB↓,
*NRF2↑, Therefore, baicalin exerts strong antioxidant activity by activating NRF2 antioxidant program.
*antiOx↑,
*Inflam↓, These data suggest that by attenuating ROS and inflammation baicalein inhibits tumor formation and metastasis.
HDAC1↓, baicalein reduced CTCLs by inhibiting HDAC1 and HDAC8 and its effect on tumor inhibition was better than traditional HDAC inhibitors
HDAC8↓,
Wnt↓, Baicalein also reduced the proliferation of acute T-lymphoblastic leukemia (TLL) Jurkat cells by inhibiting the Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
PD-L1↓, baicalein and baicalin promoted antitumor immune response by suppressing PD-L1 expression of HCC cells, thus increasing tumor regression
Sepsis↓, Baicalein can also attenuate severe sepsis via ameliorating immune dysfunction of T lymphocytes.
NF-kB↓, downregulation of NFκB and CD74/CD44 signaling in EBV-transformed B cells
LOX1↓, baicalein is considered to be an inhibitor of lipoxygenases (LOXs)
COX2↓, inhibits the expression of NF-κB/p65 and COX-2
VEGF↑, Baicalin was shown to suppress the expression of VEGF, resulting in the inhibition of PI3K/AKT/mTOR pathway and reduction of proliferation and migration of human mesothelioma cells
PI3K↓,
Akt↓,
mTOR↓,
MMP2↓, baicalin suppressed expression of MMP-2 and MMP-9 via restriction of p38MAPK signaling, resulting in reduced breast cancer cell growth, invasion
MMP9↓,
SIRT1↑, The inhibition of MMP-2 and MMP-9 expression in NSCLC cells is mediated by activating the SIRT1/AMPK signaling pathway.
AMPK↑,

5179-

BBR,

Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy

Review,

Var,

AMPK↑, Berberine has been shown to potently induce AMP-activated protein kinase (AMPK) in cancer cells
Casp3↑, TRAIL and berberine significantly activated caspase-3 and cleavage of PARP in TRAIL-resistant MDA-MB-468 BCa cells
cl‑PARP↑,
Mcl-1↓, Berberine dose-dependently induced degradation of Mcl-1 and c-FLIP
cFLIP↓,
β-catenin/ZEB1↓, Berberine efficiently inhibited nuclear accumulation of β-catenin.
Wnt↓, berberine to inhibit the WNT pathway in different cancers
STAT3↓, Berberine reduced protein levels of STAT3
mTOR↓, berberine has anti-tumor effects, through inhibition of the mTOR-signaling pathway.
Hif1a↓, HIF-1α protein expression, a well-known transcription factor critical for dysregulated cancer cell glucose metabolism, was considerably inhibited in berberine-treated colon cancer cell
NF-kB↓, Berberine also interfered with the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway and effectively inhibited colon cancer progression
SIRT1↑, Berberine was shown to upregulate some histone deacetylases (HDAC) of class II, such as sirtuin SIRT1 (sirtuin 1),
DNMT1↓, Berberine induced a decrease in activity of two DNA methylases, DNMT1 (DNA (cytosine-5)-methyltransferase 1) and DNMT3,
DNMT3A↓,
miR-29b↓, Berberine supplementation led to the miR29-b suppression, increasing insulin-like growth factor-binding protein (IGFBP1) expression in the liver;
IGFBP1↑,
eff↑, Silver nanoparticles proved successful in delivering berberine to human tongue squamous carcinoma SCC-25 cells, blocking cell cycle and increasing Bax/Bcl-2 ratio
chemoPv↑, uncovered tremendous chemopreventive ability of berberine to modulate signaling pathways
BioAv↓, Although some issues remain to be solved, such as its poor water solubility/stability and low bioavailability

4263-

CA,

Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action

Review,

AD,

*neuroP↑, neuroprotective effect of CA on neuronal cells subjected to ischemia/hypoxia injury via the scavenging or reduction of ROS (reactive oxygen species) and NO (nitric oxide) and inhibition of COX-2 and MAPK pathways
*ROS↓,
*NO↓,
*COX2↓,
*MAPK↓,
*NRF2↑, CA is known to activate the Keap1/Nrf2 pathway, thereby resulting in the production of cytoprotective proteins.
*GSH↑, activation of GSH metabolism
*HO-1↑, activation of Nrf2 target genes, including heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TXNRD1)
*5HT↑, Observations of increased serotonin and BDNF suggest that CA may represent a novel therapeutic avenue for depressive behaviors that should be further explored.
*BDNF↑, 10 μM CA results in a 1.5-fold increase in levels of BDNF
*PI3K↑, CA has been shown to mediate the activation of the PI3K/Akt/NF-κB pathway
*Akt↑,
*NF-kB↑,
*BBB↑, CA was shown to ameliorate brain edema and blood-brain barrier (BBB) disruption
*SIRT1↑, CA was also shown to increase SIRT1
*memory↑, CA was shown to significantly improve short-term and spatial memory attributes in rat models of AD
*Aβ↓, CA also delayed the deposition of Aβ and protected cells against Aβ-induced cholinergic and mitochondrial dysfunction in a Caenorhabditis elegans model of AD
*NLRP3↓, CA also inhibits the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, which plays a critical role in the pathogenesis of neurodegenerative disorders, including AD and PD and COVID-19

5834-

CAP,

Capsaicin and TRPV1: A Novel Therapeutic Approach to Mitigate Vascular Aging

Study,

Nor,

*AntiCan↑, capsaicin possesses anti-cancer, anti-inflammatory, and antioxidant properties and is used as a topical analgesic
*Inflam↓,
*antiOx↑,
*TRPV1↑, Studies demonstrate that capsaicin directly activates TRPV1 by binding to intracellular sites within the channel protein
*AMPK↑, Moreover, capsaicin and TRPV1 can activate the AMPK pathway [82, 83]
*SIRT1↑, elevating SIRT1 levels
*NADPH↓, suppressing NADPH oxidase and reducing reactive oxygen species
*ROS↓,
*MAPK↓, inhibiting MAPK pathways
*eNOS↑, activating eNOS
*Wnt/(β-catenin)↓, inhibiting the Wnt/β-catenin signaling pathway
RenoP↑, Furthermore, TRPV1 activation decreases renal perfusion pressure while increasing glomerular filtration rate and the excretion of sodium/water, thereby modulating renal hemodynamics and excretory functions

5859-

CAP,

Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?

Review,

Var,

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

5847-

CAP,

An updated review on molecular mechanisms underlying the anticancer effects of capsaicin

in-vitro,

Liver,

HepG2

HO-1↑, capsaicin induced the expression of HO-1 in human hepatoma HepG2 cells through the generation of ROS and subsequent activation of a redox-sensitive transcription factor nuclear factor erythroid related factor-2 (Nrf2)
ROS↑,
NRF2↑,
*lipid-P↓, capsaicin inhibits lipid peroxidation by increasing the activity of a battery of antioxidant enzymes
*SOD↑, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR)
*Catalase↑,
*GPx↑,
*GSR↑,
*PGE2↓, inhibitory effects of capsaicin on the production of prostaglandin E2 (PGE2) in macrophages incubated with LPS or TPA (
*COX2↓, the inhibition of COX-2 and iNOS expression by capsaicin in these cells is mediated in a VR1/TRPV1-independent manner
*iNOS↓,
TumCP↓, anticancer effects of capsaicin are partly mediated through the inhibition of cancer cell proliferation.
TumCCA↑, Capsaicin inhibited the growth of human esophageal epidermoid carcinoma (CE 81T/VGH) cells by arresting the cell cycle at the G1 phase through the downregulation of cyclin E, cyclin dependent kinase (Cdk)-4 and -6,
cycE/CCNE↓,
CDK4↓,
MMP↓, Similarly, the inhibition of Cdk-2,-4 and-6, the generation of ROS, and the loss of mitochondrial membrane potential were associated with reduced proliferation of human bladder cancer cells upon capsaicin treatment
P53↑, capsaicin is mediated through the induction of p53 nd its target gene products such as, p21, and Bax.
P21↑,
BAX↑,
SIRT1↑, The same study also demonstrated that capsaicin induced autophagy in human fetal lung cells by inducing SIRT1
angioG↓, Capsaicin inhibited angiogenesis in the chick chorioallantoic membrane
P-gp↓, Capsaicin inhibited the P-gp activity in human intestinal carcinoma (Caco2) cells in a concentration- and time-dependent manner (
ChemoSen↑, Capsaicin exhibited synergistic growth inhibitory effects with 5-fluorouracil (5FU) in cholangiocarcinoma cells in culture as well as xenograft tumor growth in nude mice

1263-

CAP,

Capsaicin inhibits the migration and invasion via the AMPK/NF-κB signaling pathway in esophagus sequamous cell carcinoma by decreasing matrix metalloproteinase-9 expression

in-vitro,

ESCC,

Eca109

TumCMig↓,
TumCI↓,
MMP9↓,
p‑AMPK↑,
SIRT1↑,
NF-kB↓, capsaicin retrains the invasion and migration of Eca109 cells by inhibiting NF-κB p65 via the AMPK-SIRT1 and the AMPK-IκBa signaling pathways, which cause MMP-9 expression inhibition.
p‑IκB↑,

5897-

CAR,

Carvacrol Selectively Induces Mitochondria-Related Apoptotic Signaling in Primary Breast Cancer-Associated Fibroblasts

in-vitro,

BC,

Bax:Bcl2↑, marked increase in the BAX/BCL-XL ratio
PPARα↓, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3
NF-kB↓,
SIRT1↑,
SIRT3↑,
MMP3↓,
selectivity↑, Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts.
Bcl-2↓, In breast cancer lines, CV has been reported to down-regulate Bcl-2, up-regulate Bax, and induce caspase-3/-6/-9 activation in a dose-dependent manner, consistent with mitochondrial apoptosis
BAX↑,
Casp3↑,
Casp6↑,
Casp9↑,
mt-Apoptosis↑,

5780-

CRMs,

HCAs,

RES,

Sper,

ASA

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Review,

Var,

*OS↑, The permanent or periodic reduction of calorie intake without malnutrition (caloric restriction and fasting) is the only strategy that reliably extends healthspan in mammals including non-human primates.
*AntiAge↑, CRMs will become part of the pharmacological armamentarium against aging and age-related cardiovascular, neurodegenerative, and malignant diseases.
*cardioP↑,
*neuroP↑,
AntiCan↑,
*TNF-α↓, In healthy humans, CR also decreases the levels of circulating tumor necrosis factor-α
*Weight↓, In obese humans, CR promotes significant weight loss and improves general health
*BP↓, Figure 1
*Inflam↓,
*Insulin↓,
*ROS↓,
*AMPK↑,
*mTOR↓,
*SIRT1↑, Resveratrol and Other SIRT1 Activators
CRM↑, Figure2: HCA, Resveratrol, Spermidine, Aspirin, Berberine, EGCG, QC, etc

5792-

CRMs,

HCA,

CUR,

EGCG,

GAR

Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers

Review,

Nor,

*CRM↓, AcCoA depleting agents (e.g., hydroxycitrate),
*Dose?, acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine)
*AntiAge↑, Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage.
*Acetyl-CoA↓, Altogether, these observations point to the idea that starvation causes autophagy because it results in the early depletion of AcCoA
*SIRT1↑, nduction of the deacetylase activity of sirtuins (as a result of changing NADH/NAD+ ratios and increased SIRT1 expression)
*AMPK↑, activation of AMPK activity (as a result of changing ATP/ADP ratios)
*mTORC1↓, inhibition of MTORC1 (as a result of amino acid depletion).
*AntiAge↑, CR or intermittent fasting are known for their wide life-span-extending
chemoP↑, fasting can reduce the subjective and objective toxicity of cytotoxic anticancer chemotherapies, both in humans and in mouse models, at the same time that it improves treatment outcome in mice

5798-

CRMs,

Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders

Review,

Nor,

Review,

AD,

*GutMicro↑, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production
*neuroP↑, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
*eff↑, ‘Mediterranean diet’ composed of unsaturated fatty acids, fibers, and antioxidants has been shown to help in longevity by shifting the GM towards Bacteroides, Bifidobacterium, and Lactobacillus, with a reduction in the members of Pseudomonadota and B
*Dose↝, AD patients displayed fewer populations of Firmicutes, Proteobacteria, and Actinobacteria, and an increased abundance of Bacteroidetes.
*AMPK↑, major routes through which CRMs function include AMPK, Sirtuin1, mTOR, and Keap1-Nrf2 pathways which have been highlighted in Fig. 2.
*SIRT1↑, CRMs can function as activators of protein (de)acetylases, particularly, SIRT1
*mTOR↓,
*NRF2↑, Quercetin, a CRM led to the activation of Nrf2 and induced expression of antioxidant enzymes.
*p‑tau↓, metformin has shown its effect in reducing tau phosphorylation by inducing protein phosphatase 2A (PP2A) expression via the AMPK/mTOR pathway

3635-

Cro,

A Review of Potential Efficacy of Saffron (Crocus sativus L.) in Cognitive Dysfunction and Seizures

Review,

NA,

*memory↑, value of saffron and its’ components, alone, or in combination with the other pharmaceuticals, for improving learning and memory abilities and controlling seizures
*cognitive↑, use of saffron in cognitive disturbance and epilepsy
*BioAv↑, Crocin is converted to crocetin by gastrointestinal cells (Hosseini et al., 2018), and is then absorbed and distributed to body tissues including the central nervous system
*ROS↓, -pretreated rats, cognitive performance was restored through attenuation of oxidative stress
*IL1↓, Crocin suppressed formation of advanced glycation products and brain inflammatory mediators [interleukin (IL)-1, tumor necrosis factor (TNF)-α, and nuclear factor (NF)-κB].
*TNF-α↓,
*NF-kB↓,
*neuroP↑, neuroprotective effects against oxidative stress was suggested to be related to increases in phosphoinositide 3-kinase/Akt and mitogen-activated protein kinases/extracellular signal-regulated kinases
*lipid-P↓, Reduced lipid peroxidation and DNA injury and restored thiol redox and antioxidant status
*Thiols↑,
*antiOx↑,
*AChE↓, restoring oxidative damage biomarkers including glutathion and lipid peroxidation as well as modulating the activities of acetylcholinesterase (AChE) and monoamine oxidase (MAO)
*MAOA↝,
*SIRT1↑, up-regulate the SIRT1/PGC-1α pathway.
*PGC-1α↑,
*Ach↑, increases synaptic acetylcholine levels

3795-

CUR,

Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence

Review,

AD,

*antiOx↑, Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties
*Inflam↓,
*AntiAge↑, Its potential anti-aging properties are due to its power to alter the levels of proteins associated with senescence, such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and sirtuins
*AMPK↑,
*SIRT1↑,
*NF-kB↓, preventing pro-aging proteins, such as nuclear factor-kappa-B (NF-κB) and mammalian target of rapamycin (mTOR)
*mTOR↓,
*NLRP3↓, Moreover, curcumin, by inhibiting the NF-κB pathway, can directly restrain the assembly or even inhibit the activation of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome
*NADPH↓, by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and elevating the activity of antioxidant enzymes and consequently lowering reactive oxygen species (ROS)
*ROS↓,
*COX2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1↓,
*IL1β↓, by decreasing IL-1β, IL-17, IL-23, TNF-α, and myeloperoxidase, enhancing levels of IL-10, and downregulating activation of NF-κB
*IL17↓,
*IL23↓,
*TNF-α↓,
*MPO↓,
*IL10↑,
*lipid-P↓, curcumin showed a significant decline in lipid peroxidation and increased superoxide dismutase levels, in addition to a reduction in Aβ aggregation and tau hyperphosphorylation through the regulation of GSK3β, Cdk5, p35, and p25
*SOD↑,
*Aβ↓,
*p‑tau↓,
*GSK‐3β↓,
*CDK5↓,
*TXNIP↓, Curcumin also has an inhibitory role on the thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway
*NRF2↑, well as upregulation of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), HO-1, and γ-glutamyl cysteine synthetase (γ-GCS) in brain cells.
*NQO1↑,
*HO-1↑,
*OS↑, significant improvement in OS, and a positive evolution in memory and spatial learning
*memory↑,
*BDNF↑, Besides that, it promoted neurogenesis through increasing brain-derived neurotrophic factor (BDNF) levels
*neuroP↑, Curcumin can promote neuroprotection
*BACE↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.

3862-

CUR,

RES,

The metalloproteinase ADAM10: A useful therapeutic target?

Review,

AD,

*SIRT1↑, Therefore, the Sirt1 activators curcumin and resveratrol are tested for their clinical impact on ADAM10 expression in AD.
*ADAM10↑,

1844-

dietFMD,

Unlocking the Potential: Caloric Restriction, Caloric Restriction Mimetics, and Their Impact on Cancer Prevention and Treatment

Review,

NA,

Risk↓, CRMs were well tolerated, and metformin and aspirin showed the most promising effect in reducing cancer risk in a selected group of patients.
AMPK↑, the increased AMP levels activate AMPK
Akt↓, This activation results in the inhibition of AKT and mTOR pathways
mTOR↓,
SIRT1↑, energy deficit also activates the SIRT pathways, which downregulates HIF1α, and the Nrf2 pathway
Hif1a↓,
NRF2↓,
SOD↑, enhances antioxidant defenses (e.g., superoxide dismutase SOD1 and SOD2)
ROS↑, Additionally, in prostate cancer (PC) [55] and triple-negative breast cancer (TNBC) [56] cell lines glucose restriction (GR) has been shown to trigger an increase in ROS, leading to cell death.
IGF-1↓, CR decreases poor prognosis markers such as IGF1, pAKT, and PI3K
p‑Akt↓,
PI3K↑,
GutMicro↑, induces changes in the gut microbiome linked to anti-tumor effects
OS↑, Incorporating a nutraceutical regimen like CR or KD with CT has reduced tumor growth and relapse and improved the survival rate
eff↝, type of dietary intervention, with FMD being the first option, followed by KD and CR last. FMD has been considered the most cost-effective and applicable because it does not completely restrict food intake.
ROS↑, findings consistently indicating that dietary restrictions render highly proliferative tumor cells more susceptible to oxidative damage
TumCCA↑, CR has been reported to induce cell cycle arrest in the G0/G1 phases , enabling cells to undergo DNA repair more efficiently and diminishing DNA damage by CRT
*DNArepair↑,
DNAdam↑, In contrast, tumoral cells, which have an altered cell cycle, are unable to repair DNA, leading to cell death

1863-

dietFMD,

Chemo,

Effect of fasting on cancer: A narrative review of scientific evidence

Review,

Var,

eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

3222-

EGCG,

Epigallocatechin gallate and mitochondria—A story of life and death

Review,

Nor,

*lipid-P↓, ↓Lipid peroxidation ↑SOD, CAT, GPx, GR, and GST, ↑GSH
*SOD↑,
*Catalase↑,
GPx↑,
*GR↑,
*GSTs↑,
*GSH↑,
*SIRT1↑, EGCG upregulated the levels of NAD+ -dependent protein deacetylase sirtuin-1 (SIRT1), peroxi- some proliferator-activated receptor co-activator-1 (PGC-1), glutathione peroxidase (GPx), and SOD in MPP + -treated PC12 cells.
*PGC1A↑,
*other↑, EGCG (2 mg/kg day-1 administered through oral gavage for 30 days) upregulated the activities of brain mitochondrial antioxidant enzymes (SOD, CAT, and GPx) in aged, but not in young rats.

3246-

EGCG,

Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway

in-vitro,

Nor,

rat

*MDA↓, EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity.
*SOD↑,
*SIRT1↑, EGCG activated SIRT1 and increased FOXO1 expression
*FOXO1↑,
*SREBP2↓, EGCG increased FOXO1 expression, and decrease SREBP-2 expression

5519-

EP,

Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions

Review,

Var,

MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

5523-

EP,

Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication

vitro+vivo,

Nor,

HUVECs

Forty male C57BL/6 mice

*MMP↑, NsPEF treatment reverses d-galactose-induced endothelial senescence by restoring mitochondrial membrane potential. marked elevation in mitochondrial membrane potential
*Hif1a↑, NsPEF activates key MNRC markers HIF-1α and SIRT1, rescuing mitochondrial-nuclear communication.
*SIRT1↑,
*ROS↓, These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells.
*AntiAge↑, These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.
*Dose↝, mice received daily nsPEF treatment (3 kV/cm) for 14 consecutive days.
*angioG↑, The nsPEF treatments stimulate skin angiogenesis in different aged rodent models.

3716-

FA,

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells

in-vitro,

IBD,

0–500 μM for 24 h

in-vivo,

NA,

*antiOx↑, Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties
*Inflam↓,
*ER Stress↓, FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells,
*other↑, FA has a protective effect on intestinal tight junctions
*angioG↑, A has been reported to induce hypoxia and enhance the angiogenesis of human umbilical vein endothelial cells (HUVEC) by increasing the expressions of HIF-1α and vascular endothelial growth factor (VEGF)
*Hif1a↑,
*VEGF↑,
*NO↓, suggesting FA attenuates NO production induced by inflammation.
*SIRT1↑, Another study suggested that FA activated SIRT1 to protect the heart from the adverse effects of ER stress via reduction of PERK/eIF2α/ATF4/CHOP pathway
*PERK↓,
*ATF4↓,
*CHOP↓,
*GutMicro↑, FA can mitigate intestinal inflammation, promote the growth of Bacteroides, and induce the production of SCFAs by modulating the gut microbiota in mouse and diabetic syndrome rat model

5148-

GamB,

Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics

Review,

Var,

AntiCan↑, In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent.
angioG↓, anti-angiogenesis, and chemo-/radiation sensitizer activities
ChemoSen↑, Moreover, GA has shown chemotherapy/radiation sensitization properties in different types of cancers
RadioS↑,
VEGF↓, Figure 2
MMP2↓,
MMP9↓,
Telomerase↓,
TrxR↓,
ERK↓,
HSP90↓,
ROS↑,
SIRT1↑,
survivin↓,
cFLIP↓,
Casp3↑,
Casp8↑,
Casp9↑,
BAD↓,
BID↓,
Bcl-2↓,
BAX↑,
STAT3↓,
hTERT/TERT↓,
NF-kB↓,
Myc↓,
Hif1a↓,
FOXD3↑,
BioAv↓, Unfortunately, the aqueous solubility of GA (0.013 mg/mL) is very low, thus limiting its clinical application.
BioAv↑, For example, GA can be coupled with alkanolamines to improve aqueous solubility and achieve equivalent anti-proliferation effects
P53↑, This inhibition was co-related with increase of p53 levels and reduced bcl-2 levels
eff↓, Such effect was received for GA due to production of ROS which can be removed by N-acetyl-L-cysteine (NAC, a ROS inhibitor)
OCR↓, GA exhibited a dose-dependent generation of intracellular ROS levels and lowered the oxygen consumption rate and the mitochondrial membrane potential.
MMP↓,
PI3K↓, GA happens to promote antimetastasis properties in melanoma cells by active inhibition of PI3K/Akt and ERK signaling pathways
Akt↓,
BBB↑, This study demonstrated successful uptake of GA through blood-brain barrier (BBB)
TumCG↓, GA-based nanomedicine is efficient in targeting tumors, capable to inhibit tumor growth, metastasis, angiogenesis, and reverse drug resistance
TumMeta↓,
BioAv↑, deliver GA using nanoparticles for enhanced solubility, bioavailability, adsorption and tumor imaging and targeting

3770-

H2,

Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases

Review,

AD,

Review,

Park,

*antiOx↑, antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level
*NRF2↑, activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes.
*HO-1↑,
*Inflam↓, hydrogen may prevent inflammation
*neuroP↑, prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer.
*cardioP↑,
*other↓, It also prevented ischemia-reperfusion (I/R) injury and stroke in a rat model
*ROS↓, H2 has been shown to exert its beneficial effects in various pathological conditions that involve free radicals and oxidative stress
*NADPH↓, figure 2, H2 Inhibits NADPH Oxidase Activity
*Catalase↑,
*GPx1↑,
*NO↓, H2 Indirectly Reduces Nitric Oxide (NO) Production
*mt-ROS↓, H2 Decreases Mitochondrial ROS
*SIRT3↑, In the kidneys, H2 suppressed the downregulated Sirt3 expression, which is the most abundant member of the sirtuin family, by reducing oxidative stress reactions
*SIRT1↑, In the liver, H2 elevated HO-1 to induce Sirt1 expression
*TLR4↓, H2 inhibits TLR4, which involves hyperglycemia in type 2 diabetes mellitus
*mTOR↓, For example, H2 inhibits mTOR, activates autophagy, and alleviates cognitive impairment resulting from sepsis
*cognitive↑,
*Sepsis↓,
*PTEN↓, It inhibits the activation of the PTEN/AKT/mTOR pathway and alleviates peritoneal fibrosis
*Akt↓,
*NLRP3↓, It also facilitates autophagy-mediated NLRP3 inflammasome inactivation and alleviates mitochondrial dysfunction and organ damage
*AntiAg↑, antiageing mechanism of H2 and the influence on ageing hallmarks are summarized in Figure 3.
*IL6↓, significantly suppressed inflammatory cytokines (IL-6, TNF-α, and IL-1β), MDA, and 8-OHdG, and improved memory dysfunction
*TNF-α↓,
*IL1β↓,
*MDA↓,
*memory↑,
*FOXO3↑, HRW can also upregulate Sirt1-Forkhead box protein O3a (FOXO3a
TumCG↓, H2 inhibits lung cancer progression
*LDL↓, Decreases oxidized LDL; improves HDL function

3773-

H2,

Role and mechanism of molecular hydrogen in the treatment of Parkinson’s diseases

Review,

Park,

*neuroP↑, potential neuroprotective effects, attributed to its selective antioxidant and anti-inflammatory properties.
*antiOx↑,
*Inflam↓,
*ROS↓, potential of molecular hydrogen to attenuate oxidative stress,
*NADPH↓, via the inhibition of NADPH oxidase activity
*NRF2↑, it also enhances the endogenous defense system by modulating the Nrf2/ARE pathway.
*BBB↑, easily penetrate the blood–brain barrier
*IL1β↓, H₂ significantly reduces the release of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, NF-κB, and HMGB1,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*NLRP3↓, hydrogen can mitigate neuroinflammation by inhibiting the NLRP3 inflammasome pathway
*Sepsis↓, hydrogen intervention in sepsis models
*p‑mTOR↓, inhibits the phosphorylation level of mTOR (indicated by a decrease in the p-mTOR/mTOR ratio) while activating the AMPK s
*AMPK↑,
*SIRT1↑, hydrogen-rich water alleviates intestinal oxidative stress by upregulating the expression of SIRT1, Nrf2, and HO-1
*HO-1↑,

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),

3776-

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↓,
*NLRP3↓, hydrogen could inhibit the activation of NLRP3 inflammasome in AD brains
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a
*SIRT1↑,
*FOXO3↑,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling
*BDNF↑, by reducing the decline in brain estrogen levels, estrogen receptor (ER) β, 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.

2891-

HNK,

Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs

Review,

Var,

AntiCan↑, honokiol possesses anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity.
Inflam↓,
antiOx↑,
selectivity↑,
*toxicity↓,
cycD1/CCND1↓, honokiol resulted in inhibition of UVB-induced expression levels of cyclins (cyclins D1, D2, and E) and CDKs in skin tumors
cycE/CCNE↓,
CDK2↓,
CDK4↓,
TumMeta↓, Honokiol Inhibits Metastatic Potential of Melanoma Cells
NADPH↓, Honokiol not only reduces the NADPH oxidase activity
MMP2↓, honokiol treatment reduces the expression of MMP-2 and MMP-9
MMP9↓,
p‑mTOR↓, honokiol caused significant downregulation of mTOR phosphorylation
EGFR↓, honokiol decreases the expression levels of total EGFR
EMT↓, honokiol effectively inhibits EMT in breast cancer cells
SIRT1↑, onokiol increases the expressions of SIRT1 and SIRT3,
SIRT3↑,
EZH2↓, depletion of EZH2 by honokiol treatment inhibited cell proliferation
Snail↓, significantly down regulates Snail, vimentin, N-cadherin expression, and upregulates cytokeratin-18 and E-cadherin expression
Vim↓,
N-cadherin↓,
E-cadherin↑,
COX2↓, honokiol as an inhibitor of COX-2 expression
NF-kB↓, inhibited transcriptional activity of NF-jB,
*ROS↓, Inhibition of UVR-induced inflammatory mediators as well as ROS by honokiol treatment contributes to the prevention of UVR-induced skin tumor development
Ca+2↑, excessive influx of cytosolic calcium ion into the mitochondria triggers dysfunction of the mitochon- drial membrane permeabilization with mitochondrial ROS induction
ROS↑,

4338-

LT,

Luteolin: a natural product with multiple mechanisms for atherosclerosis

Review,

NA,

*Inflam↓, Figure 2
*ROS↓,
*PDGF↓, luteolin 7-glucoside (L7G) can inhibit PDGF-BB-induced VSMC proliferation and DNA synthesis by blocking the phosphorylation of PLC-γ1, Akt, and Erk1/2, ultimately inhibiting VSMC proliferation.
*lipid-P↓, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
*AMPK↑, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
*SIRT1↑,
*AntiAg↑,

2921-

LT,

Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies

Review,

Nor,

*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

3277-

Lyco,

Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent

Review,

Var,

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

2938-

NAD,

NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling

in-vivo,

BC,

TumMeta↓, NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model
SIRT1↑, NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.

2932-

NAD,

Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment

in-vitro,

Nor,

using 661W cells

*SIRT1↑, NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression.
*HO-1↑,
*neuroP↑, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.
*Apoptosis↓, NMN at 250 mg/kg reduced cell death numbers by 52.7% (2292 ± 690 cells/mm2, p<0.001) whereas NMN at 500 mg/kg decreased cell death by 71.0% (1405 ± 290 cells/mm2, p<0.001).
*Inflam↓, NMN supplementation suppresses retinal inflammation
*ROS↓, NMN normalizes oxidative stress and upregulates antioxidant HO-1 after RD
*antiOx↑, These results suggested that SIRT1 is at least partially responsible for the antioxidant property of NMN.
*toxicity↓, A study of one-year oral administration of NMN showed safe and well-tolerated effects in wild-type C57BL/6 mice, and human clinical studies have been performed with no apparent negative effects

2933-

NAD,

Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns

Review,

Nor,

NA,

AD,

NA,

Diabetic,

NA,

Stroke,

NA,

LiverDam,

NA,

Park,

*mtDam↓, The mitochondrial decay, which is responsible for aging, can be reversed by the increased levels of nicotinamide adenine dinucleotide (NAD+) in the body.
*BioAv↝, NMN is a precursor of NAD+ that acts as an intermediate in NAD+ biosynthesis, while dietary supplements of NMN are found to increase the NAD+ levels in the body
*BioAv↑, molecular weight is 334.22 g/mol. It is fairly acidic and water-soluble compound. The solubility has been reported to be 1.8 mg/mL
*OS↑, plays a vital role in a variety of biological processes of the body including cell death, aging, gene expression, neuroinflammation and DNA repair, which indicating a significance role of NAD+ in longevity and health of human life
*eff↑, NMN has therapeutic effects towards a range of diseases, including age-induced type 2 diabetes, obesity, cerebral and cardiac ischemia, heart failure and cardiomyopathies
*eff↑, Alzheimer’s disease and other neurodegenerative disorders, corneal injury, macular degeneration and retinal degeneration, acute kidney injury and alcoholic liver disease
*cognitive↑, cognitive impairments, DNA damage and sirtulin gene inactivation, are brought about by aging which can be evaded by enhancing NAD+ count in the body
*DNAdam↓,
*SIRT1↑, NMN, the NAMPT reaction product, is able to be utilised to trigger the SIRT1 activity
*cardioP↑, NMN also can restore gene expression linked to circadian rhythm, inflammatory response and oxidative stress, and improve hepatic insulin sensitivity, partially by SIRT1 activation.
*ROS↓, NMN has been proven to reduce DNA damage and accumulation of ROS
*Dose↝, NMN in available commercial products vary from 50 to 150 mg/capsule, whereas some consumers take two 150 mg capsules per day
*BioAv↑, NMN was speedily absorbed in the small intestine by a specific transporter, which was encoded by the Slc12a8 gene as demonstrated in in vitro and in vivo studies
*hepatoP↑, NMN supplementation has been found to have significant recovering effects on hepatocyte functions and liver pathologies in early-stage of ethanol toxicity, instead of causing adverse effects to the liver
*eff↑, supplementation of NMN has been found to be a promising therapeutic remedy for PD
*BG↓, Oral administration of NMN increased serum bilirubin contents and decreased blood glucose, chloride and serum creatinine levels, but within the normal range.
*creat↓,

2936-

NAD,

The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

*ROS↓, vitro/in vivo studies have demonstrated that NMN supplementation increases NAD+ concentration and could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and inflammatory responses.
*DNAdam↓,
*neuroP↑, NAD+ concentrations in the human brain declined 10% to 25% from young adulthood to old age
*Inflam↓,
*BioAv↑, In fact, it has been shown that caloric restriction increases NAD+ bioavailability by activating
*SIRT1↑, whereas it lowers NADH levels and activates sirtuins to extend the life span of yeast
BioAv↝, NR holds an edge over NMN because cells cannot directly absorb NMN, and NMN must be converted to NR before entering cells.

2937-

NAD,

High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1-AMPK-ACC Pathway

in-vitro,

Lung,

A549

SIRT1↑, Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1–AMPK–ACC signaling
Dose↝, At low doses (10 and 20 mM) and prolonged exposure (48 h), NMN increased cell proliferation, but it induced the suppression of cell proliferation at the high dose (100 mM)
TumCP⇅,
Ferroptosis↑, High-Dosage NMN Inhibits Lung Cancer Growth by Inducing Ferroptosis Program
lipid-P↑, high-dose NMN increased lipid peroxide accumulation in the A549 and SPCA1 cells.
AMPK↑, high-dose NMN treatment can activate SIRT1–AMPK–ACC signaling mediated through an overload of NAM.
ACC↑,

3587-

PI,

Piperine: A review of its biological effects

Review,

Park,

Review,

AD,

*hepatoP↑, piperine has also been documented for its hepatoprotective, anti-allergic, anti-inflammatory, and neuroprotective properties
*Inflam↓,
*neuroP↑,
*antiOx↑, antiangiogenesis, antioxidant, antidiabetic, antiobesity, cardioprotective,
*angioG↑,
*cardioP↑,
*BioAv↑, nano-encapsulation and resulting piperine-loaded nanoparticles enhance the bioavailability of piperine via oral administration
*P450↓, piperine inactivates cytochrome P450 (CYP) 3A (CYP3A), which plays a critical role in drug metabolism
*eff↑, enhances the anti-inflammatory effects when combined with resvera- trol
*BioAv↑, piperine increases the bioavailability of various compounds such as ciprofloxacin, norfloxacin, metronidazole, oxytetracycline, nimesulide, pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin, gallic acid, tiferron, nevirapine, and sparte
E-cadherin↓, Downregulates the E-cadherin (E-cad), estrogen receptor (ER), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP- 9), vascular endothelial growth factor (VEGF) levels, and c-Myc.
ER(estro)↓,
MMP2↓,
MMP9↓,
VEGF↓,
cMyc↓,
BAX↑, Increases the expressions of Bax and p53.
P53↑,
TumCG↓, Lowers the tumor growth and elevates survival time
OS↑,
*cognitive↑, piperine ameliorated the neuro-chemical, neuroinflammatory, and cognitive alterations caused by chronic exposure to galactose
*GSK‐3β↓, piperine reversed D-Gal-induced GSK-3Î² activation through modulating PKC and PI3K/AKT pathways, s
*GSH↑, Piperine stimulates glutathione levels in rats' striatum, reduced caspase-3 and 9 activation, and diminished release of cytochrome-c from mitochondria along with a reduction in lipid peroxidation
*Casp3↓,
*Casp9↓,
*Cyt‑c↓,
*lipid-P↓,
*motorD↑, piperine also caused improvement in motor coordination and balance behavior along with reduction in contralateral rotations.
*AChE↓, significantly amended impaired memory and hippo-campus neurodegeneration and lowered lipid peroxidation and acetylcholinesterase enzyme
*memory↑,
*cardioP↑,
*ROS↓, fig 6
*PPARγ↑,
*ALAT↓, piperine lowers alanine aminotransferase (ALT), AST, and ALP levels in sera of cholesterol-fed albino mice
*AST↓,
*ALP↓,
*AMPK↑, reversed the downregulation of AMPK signaling molecules, which are responsible for fatty acid oxidation, insulin signaling, and lipogenesis in mouse liver.
*5HT↑, t causes a significant decrease in serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) contents in the hippocampus and frontal cortex.
*SIRT1↑, , it may enhance the SIRT1 expression in cells and SIRT1 activity enhancing its potential to prevent SIRT1-mediated disease
*eff↑, combination ther- apy of resveratrol and piperine as an approach to enhance the biologi- cal effects with respect to cerebral blood flow and improved cognitive functions

2963-

PL,

Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

in-vitro,

AD,

HEK293

50 mg/kg/day for 2.5 months

mice

*SIRT1↑, Piperlongumine (PL) activates the deacetylase ability of Sirt1 in vitro.
*cognitive↑, PL improves cognitive deficits in APP/PS1 mice.
*Aβ↓, PL reduces amyloid deposition and neuro-inflammation in the brain of APP/PS1 mice.
*Inflam↓,
*neuroP↑,
memory↑, Sirt1 has been shown to modulate synaptic plasticity and memory formation
Dose↓, PL induced Sirt1 deacetylase activity at a relatively low concentration, i.e. 1.5 uM, compared to the resveratrol treatment.
NAD↑, PL treatment at doses of 0.5 and 4 Î¼M significantly increased the level of NAD + . These results indicate that PL might activate Sirt1, subsequently changing the NAD + /NADH ratio

2338-

QC,

Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury

Review,

Nor,

*SIRT1↑, Quercetin increased SIRT1 expression in lung tissue, inhibited NLRP3 inflammasome activation, and reduced the release of pro-inflammatory factors (TNFα, IL-1β, and IL-6), preventing the up-regulation of nuclear PKM2 in the lung.
*NLRP3↓,
*Inflam↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*PKM2↓, preventing the up-regulation of nuclear PKM2 in the lung.
*HO-1↑, Quercetin increased HO-1 expression in the lungs of a septic lung injury mouse model
*ROS↓, puncture in rats, showing that early administration of Quercetin reduced the levels of oxidative stress markers, such as xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA), and increased the levels of antioxidant enzymes in lung tiss
*NO↓,
*MDA↓,
*antiOx↑,
*COX2↓, Quercetin also reduced the expression of COX-2, HMGB1, and iNOS expression and NF-κB p65 phosphorylation
*HMGB1↓,
*iNOS↓,
*NF-kB↓,

5025-

QC,

New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation

Review,

Nor,

*antiOx↑, Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.
*Inflam↓,
*NRF2↓,
*ROS↓, Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs.
*cardioP↑, Nrf2 promotes the proliferation and repair of vascular smooth muscle cells, effectively restoring the optimal structure and function of blood vessels to improve cardiovascular health.
*HO-1↑, Que interacts with antioxidant enzymes such as HO-1, CAT, and glutathione peroxidase (GSH-PX), and enhances their free radical scavenging activity
*Catalase↑,
*GPx↑,
*NQO1↑, This process upregulates the expressions of key antioxidant and detoxification genes, such as HO-1 and NQO1, thereby inhibiting excessive intracellular ROS production.
*SIRT1↑, Que mediated by the activation of the Sirt1/Nrf2/HO-1 pathway,

3607-

QC,

Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More

Review,

AD,

Review,

Park,

*neuroP↑, supportive evidence for neuroprotective effects of quercetin
*NRF2↑, nduction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2).
*PONs↑,
*antiOx↑,
*Inflam↓,
*SIRT1↑, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection.
*eff↑, Additionally, coadministration of quercetin and alpha-tocopherol has been shown to increase the transport of quercetin across the blood-brain barrier
*ROS↓, was shown to protect rodents from oxidative stress
*cognitive↑, quercetin ameliorates Alzheimer's disease pathology and related cognitive deficits in an aged triple transgenic Alzheimer's disease mouse model
*eff↑, combined oral supplementation of quercetin and fish oil enhanced neuroprotection in rats exposed to 3-nitropropionic acid
*lipid-P↓, Decreased lipid perox. in hippocampus;
*GSH↑, Decreased reduction of GSH, GPx (5, 50 mg/kg)
*GPx↑,
*SOD↑, Diminished reduction of DA levels, SOD, and GPx
*NRF2↑, Quercetin has been shown to counteract oxidative stress-induced cellular damage by activating the Nrf2-ARE pathway

3534-

QC,

Lyco,

Synergistic protection of quercetin and lycopene against oxidative stress via SIRT1-Nox4-ROS axis in HUVEC cells

in-vitro,

Nor,

HUVECs

*ROS↓, especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production.
*NOX4↓, Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress
*Inflam↓, quercetin-lycopene combination downregulated inflammatory genes induced by H2O2, such as IL-17 and NF-κB.
*NF-kB↓, NF-κB p65 was activated by H2O2 but inhibited by the quercetin-lycopene combination.
*p65↓,
*SIRT1↑, quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity
*cardioP↑, The cardioprotective role of SIRT1
*IL6↓, LYP: Q = 1:5), interacted with deacetylase SIRT1 to inhibit NF-κB p65 and Nox4 enzyme, downregulated inflammatory cytokines such as IL-6 and pro-inflammatory enzymes such as COX-2, and suppressed ROS elevation activated by H2O2.
*COX2↓,

3350-

QC,

Quercetin and the mitochondria: A mechanistic view

Review,

NA,

*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*NRF2↑, Quercetin is able to activate the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2)
ROS⇅, That is, as a free radical-scavenging antioxidant, quercetin protects cells against DNA damage induced by reactiveoxygen species (ROS), but the oxidized quercetin intermediates (see above) can then react with glutathione (GSH) thereby lowering GSH
*NRF2↑, 10uM (24 h) Mouse primary hepatocytes Activation of Nrf2; ↑HO-1 levels; ↑expression of PPARÎ± and PGC-1Î±
*HO-1↑,
*PPARα↑,
*PGC-1α↑,
*SIRT1↑, Rat hippocampus ↑ SIRT1, PGC-1Î±, NRF-1, and TFAM levels; ATP levels;
*ATP↑,
ATP↓, L1210 and P388 leukemia cells (Suolinna et al., 1975). At least in part, the authors attributed the pro-apoptotic effect of quercetin in these cell lines to its capacity to inhibit ATP synthase, causing a decrease in ATP content.
ERK↓, downregulation of ERK1/2 by quercetin (50-100 uM for 24 or 48 h, combined or not with resveratrol
cl‑PARP↑, NCaP cells ↑PARP cleavage ↑ Caspase-9, caspase-8, and caspase-3 activities
Casp9↑,
Casp8↑,
BAX↑, MDA-MB-231 cells ↑Bax levels, ↓MMP, ↑cytochrome c release, ↑caspase-9 and caspase-3 activities
MMP↓,
Cyt‑c↑,
Casp3↑,
HSP27↓, T98G cells: ↓Hsp27 and Hsp72 contents, ↓Ras and Raf level
HSP72↓,
RAS↓,
Raf↓,

Showing Research Papers: 1 to 50 of 97
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 97

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1, Sepsis↓, 1,
Total Targets: 216

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 19, Catalase↑, 5, GPx↑, 4, GPx1↑, 1, GSH↑, 5, GSR↑, 1, GSTs↑, 1, HO-1↑, 10, lipid-P↓, 8, lipid-P↑, 1, MDA↓, 6, MPO↓, 2, NOX4↓, 1, NQO1↑, 3, NRF2↓, 1, NRF2↑, 13, ROS↓, 26, ROS↑, 1, mt-ROS↓, 1, SIRT3↑, 2, SOD↑, 7, Thiols↑, 1, UCPs↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1, Insulin↓, 1, MMP↑, 1, mtDam↓, 2, PGC-1α↑, 2,

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1, ALAT↓, 3, AMPK↑, 12, cAMP↑, 1, CRM↓, 1, LDL↓, 2, NADPH↓, 4, PGC1A↑, 1, PKM2↓, 1, PONs↑, 1, PPARα↑, 2, PPARγ↑, 2, SIRT1↑, 34, SREBP1↓, 1, SREBP2↓, 1,

Cell Death ⓘ

Akt↓, 1, Akt↑, 1, p‑Akt↑, 1, Apoptosis↓, 2, Casp1↓, 1, Casp3↓, 2, Casp9↓, 2, Cyt‑c↓, 1, iNOS↓, 4, JNK↓, 2, MAPK↓, 2, p38↓, 1, p‑p38↓, 1, TRPV1↑, 2,

Transcription & Epigenetics ⓘ

Ach↑, 2, other↓, 1, other↑, 2,

Protein Folding & ER Stress ⓘ

CHOP↓, 2, ER Stress↓, 2, PERK↓, 1,

DNA Damage & Repair ⓘ

ATM↑, 1, DNAdam↓, 2, DNArepair↑, 1,

Proliferation, Differentiation & Cell State ⓘ

CD34↑, 1, FOXO↑, 1, FOXO1↑, 2, FOXO3↑, 4, GSK‐3β↓, 2, mTOR↓, 4, p‑mTOR↓, 1, mTORC1↓, 1, PI3K↑, 1, PTEN↓, 1, Wnt/(β-catenin)↓, 1,

Migration ⓘ

AntiAg↑, 2, Ca+2↑, 1, CDK5↓, 1, Na+↑, 1, PDGF↓, 1, TXNIP↓, 2, ZO-1↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 3, ATF4↓, 2, eNOS↑, 1, Hif1a↑, 4, NO↓, 5, VEGF↓, 1, VEGF↑, 1,

Barriers & Transport ⓘ

BBB↑, 3, Na+↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 6, HMGB1↓, 1, IFN-γ↓, 1, IL1↓, 1, IL10↑, 1, IL17↓, 1, IL18↓, 1, IL1β↓, 6, IL2↓, 2, IL23↓, 1, IL6↓, 8, INF-γ↓, 1, Inflam↓, 24, MCP1↓, 1, NF-kB↓, 9, NF-kB↑, 1, p65↓, 1, PGE2↓, 2, TLR2↓, 1, TLR4↓, 2, TNF-α↓, 10,

Synaptic & Neurotransmission ⓘ

5HT↑, 2, AChE↓, 3, ADAM10↑, 1, BDNF↑, 5, ChAT↑, 1, MAOA↝, 1, p‑tau↓, 2,

Protein Aggregation ⓘ

Aβ↓, 4, BACE↓, 1, NLRP3↓, 9,

Hormonal & Nuclear Receptors ⓘ

ER(estro)↑, 1, GR↑, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 7, BioAv↝, 1, Dose?, 1, Dose↝, 4, eff↑, 9, Half-Life↓, 1, P450↓, 1,

Clinical Biomarkers ⓘ

ALAT↓, 3, ALP↓, 1, AST↓, 3, BG↓, 1, BP↓, 1, creat↓, 1, GutMicro↑, 4, IL6↓, 8,

Functional Outcomes ⓘ

AntiAge↑, 6, AntiCan↑, 1, cardioP↑, 7, cognitive↑, 10, hepatoP↑, 4, memory↑, 7, motorD↑, 1, neuroP↑, 14, OS↑, 3, toxicity↓, 3, Weight↓, 1,

Infection & Microbiome ⓘ

Sepsis↓, 2,
Total Targets: 154

Scientific Paper Hit Count for: SIRT1, Sirtuin 1 protein

34 Resveratrol
6 Quercetin
5 Hydrogen Gas
5 nicotinamide adenine dinucleotide
5 Urolithin
4 Capsaicin
4 Curcumin
4 EGCG (Epigallocatechin Gallate)
4 Thymoquinone
3 Calorie Restriction Mimetics
2 Silver-NanoParticles
2 Alpha-Lipoic-Acid
2 diet FMD Fasting Mimicking Diet
2 Electrical Pulses
2 Luteolin
2 Lycopene
2 Silymarin (Milk Thistle) silibinin
2 Shikonin
1 Magnetic Fields
1 Allicin (mainly Garlic)
1 Andrographis
1 Artemisinin
1 Baicalein
1 Baicalin
1 Berberine
1 Carnosic acid
1 Carvacrol
1 Hydroxycinnamic-acid
1 Spermidine
1 Aspirin -acetylsalicylic acid
1 HydroxyCitric Acid
1 Garcinol
1 Crocetin
1 Chemotherapy
1 Ferulic acid
1 Gambogic Acid
1 Honokiol
1 Piperine
1 Piperlongumine
1 Radiotherapy/Radiation
1 Sesame seeds and Oil
1 Salvia miltiorrhiza
1 Vitamin B3,Niacin

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#:634  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

SIRT1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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