PGC-1α Cancer Research Results

PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha: Click to Expand ⟱

Source:

Type: transcriptional coactivator

PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator that plays a crucial role in regulating cellular energy metabolism, including mitochondrial biogenesis and function. PGC-1α is also involved in various cellular processes, including cell growth, differentiation, and survival.

In some cancers (for example, certain melanomas, breast cancers, and prostate cancers), elevated levels of PGC-1α have been observed.
– Increased PGC-1α may enhance mitochondrial function and support the energetic and biosynthetic demands of tumor cells, especially under metabolic stress or during metastasis.

Scientific Papers found: Click to Expand⟱

3441-

ALA,

α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice

in-vivo,

AD,

mice

*tau↓, α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research
*GlucoseCon↑, chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brain
*GLUT3↑,
*GLUT4↑,
*VEGF↑,
*HO-1↑,
*Glycolysis↑, LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1).
*HK1↑, Our results indicated that the activity of HK was significantly increased after 10 mg/kg LA treatment.
*PGC-1α↑,
*Hif1a↑, found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.
*neuroP↑,

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

3708-

dietSTF,

Fasting as a Therapy in Neurological Disease

*PGC-1α↑, figure 1
*AMPK↑,
*adiP↑,
*glucose↓,
*Insulin↓,
*mTOR↓,
*IL6↓,
*TNF-α↓,
*cognitive↑, or even enhanced—cognitive performance
*Inflam↓, fasting suppresses inflammation, reducing the expression of pro-inflammatory cytokines such as interleukin 6 (IL6) and tumor necrosis factor α (TNFα)
*eff↑, mice fasted on alternate days can eat twice as much on the feeding day, such that their net weekly calorie intake remains similar to mice fed ad libitum; despite the lack of overall calorie restriction, the former still display beneficial metabolic e
*neuroP↑, Fasting can also prevent and treat many neurological disorders in animals;
ChemoSen↑, fasting has been shown to improve the therapeutic responses of a variety of rodent cancer models, including gliomas, to chemotherapy
eff↓, shorter nightly fasts were associated with an increased recurrence of cancer
chemoP↑, fasting before or after chemotherapy decreased chemotherapy-related adverse effects, such as weakness, fatigue, and gastrointestinal upset
*eff↑, implementation of a fasting regimen after a traumatic brain injury confers neuroprotection and improves functional recovery

2395-

EGCG,

EGCG inhibits diabetic nephrophathy through up regulation of PKM2

Study,

Diabetic,

*PKM2↑, pigallocatechin (EGCG), isolated from Green tea, increases Pyruvate kinase M2 (PKM2) expression, decreases toxic glucose metabolites, mitochondrial dysfunction and apoptosis, augments glycolytic flux and PGC-1α levels
*Apoptosis↓,
*PGC-1α↑,

2512-

H2,

Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch

in-vivo,

asthmatic,

selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

2505-

H2,

Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis

Trial,

CRC,

55 patients with histologically and clinically diagnosed stage IV colorectal carcinoma were enrolled between July 2014 and July 2017

PGC-1α↑, hydrogen gas was recently reported to activate PGC‑1α,
Dose↝, hydrogen gas for 3 h/day at their own homes and received chemotherapy
CD8+↑, Notably, hydrogen gas decreased the abundance of exhausted terminal PD‑1+ CD8+ T cells, increased that of active terminal PD‑1‑ CD8+ T cells, and improved PFS and OS times,
OS↑,

2504-

H2,

Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD-1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer

Trial,

Lung,

A total of 42 of 56 patients with lung cancer treated with nivolumab received hydrogen gas

CD8+↑, As previously reported, hydrogen gas improves the prognosis of patients with cancer by restoring exhausted CD8+ T cells into active CD8+ T cells
OS↑, Median survival time (MST) for the HGN-treated patients was 28 months, a length that is approximately 3-fold longer than that for NO-treated patients (MST 9 months)
eff↝, (PDT+ ratio and CoQ10 ratio, respectively) revealed that patients with low PDT+ ratio (<0.81) and high CoQ10 ratio (>1.175) had significantly longer OS compared with those with high PDT+ ratio and low CoQ10 ratio
CoQ10↑, Hydrogen gas has been suggested to enhance the clinical efficacy of nivolumab by increasing CoQ10 (mitochondria) to reduce PDT+, with PDT+ and CoQ10 as reliable negative and positive biomarkers of nivolumab, respectively.
PDT+↓,
PGC-1α↑, As hydrogen gas is reported to activate PGC1-α (14), it is also one of the mitochondrial activation mediators.
Dose↝, Patients were continuously treated with nivolumab (1 mg/kg) every 2 weeks. Patients also inhaled hydrogen gas 3 h daily at their home through a cannula or mask that they rented or purchased and connected to a Hycellvator ET 100
*toxicity∅, Recently, hydrogen gas inhalation was used in patients with post-cardiac arrest syndrome, and adverse events were not observed

3761-

H2,

Therapeutic Inhalation of Hydrogen Gas for Alzheimer's Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study

Human,

AD,

inhaled 3% H2 gas for one hour twice daily for 6 months

*cognitive↑, the mean individual ADAS-cog change showed significant improvement after 6 months of H2 treatment (−4.1) vs. untreated patients (+2.6).
*BBB↑, H2 has the ability to cross the blood-brain barrier (BBB) by gaseous diffusion without a specific drug delivery system
*ROS↓, An oxidized form of porphyrin catalyzes the reaction of H2 with hydroxyl radicals, the most oxidative free radicals, to reduce the oxidative stress.
*NRF2↑, secondary anti-oxidative function, H2 activates NF-E2-related factor 2 (Nrf2) [9], which reduces oxidative stress through the expression of a variety of anti-oxidant enzymes
*Inflam↓, H2 relieves inflammation by decreasing pro-inflammatory cytokines [38].
*NFAT↓, resulting in suppressing the nuclear factor of activated T cell (NFAT) transcription pathway to down-regulate pro-inflammatory cytokines
*FAO↓, H2 inhibits the free radical chain reaction, resulting in a decrease in fatty acid peroxidation and its end-products such as 4-hydroxyl-nonenal (4-HNE),
*4-HNE↓,
*PGC-1α↑, In turn, the decrease in 4-HNE promotes the expression of PGC-1α, followed by increasing FGF21,
*Ferroptosis↓, H2 has an anti-cell-death function by inhibiting ferroptosis through a decrease in peroxide [36], and by down- and up-regulating pro- and anti-death factors, respectively

4238-

HNK,

Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint

Review,

AD,

NA,

Park,

*BDNF↑, honokiol treatment led to an improvement in plasma BDNF levels.
*hepatoP↑, prevented liver damage by reducing transaminase levels (ALT and AST), liver OS, and TNF-α activity in mice challenged with LPS.
*ALAT↓,
*AST↓,
*TNF-α↓,
*SIRT3↑, 0.5, 1, 2, 5, 10 and 20 μM Enhanced SIRT3 expression, reduced Aβ levels
*Aβ↓,
*Apoptosis↓, Honokiol exhibited a dose-dependent reduction in hippocampal neural apoptosis, ROS generation, and decline in the membrane potential of mitochondria caused by AβO
*ROS↓,
*MMP↑,
*Ca+2↓, Dose-dependent reduction of ROS, suppression of intracellular Ca elevation, and inhibition of caspase-3 activity
*Casp3↓,
*Ach↑, Increased extracellular acetylcholine release to 165.5 ± 5.78% of the basal level
*PPARγ↑, Increased the expression of PPARγ and PGC1α
*PGC-1α↑,
*motorD↑, Improvement of motor dysfunction due to reversal of nigrostriatal dopaminergic neuronal loss
*TNF-α↓, Attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro
*IL1β↓,

2872-

HNK,

Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

in-vivo,

ALS,

mice

NA,

Stroke,

NA,

AD,

NA,

Park,

*eff↑, Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease
*ROS↓, honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway.
*GSH↑,
*NRF2↑,
*motorD↑, Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function
*OS↑,
*neuroP↑, honokiol exerted neuroprotection in ALS models.
*BBB↑, due to its strong lipophilic property, honokiol can readily permeate the blood–brain barrier and blood–cerebrospinal fluid barrier.
*cognitive↑, honokiol was shown a beneficial effect on the cognitive impairment in APP/PS1 via ameliorating the mitochondrial dysfunction
*eff↑, Furthermore, honokiol was applied for patent (200310121303.0) for ischemic stroke treatment, and the clinical trials would be started soon in China
*antiOx↑, Honokiol showed strong antioxidant capacity in vitro and protected the yeast against H2O2 induced oxidative damage
*Cyt‑c↑, cytoplasmic release of cytochrome c was markedly decreased
*PGC-1α↑, 10 μmol/L and significantly upregulated the PGC-1α, NRF1, and TFAM protein

2869-

HNK,

Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's

Review,

AD,

Review,

Park,

*neuroP↑, neuroprotective, anti-oxidant, anti-apoptotic, neuromodulating, anti-inflammatory, and many more qualities, honokiol,
*Inflam↓,
*motorD↑, degradation of dopaminergic neurons in Parkinson's disease and improving motor function.
*Aβ↓, Alzheimer's disease, honokiol showed promise in lowering the production of amyloid-beta (Aβ) plaques, phosphorylating tau, and enhancing cognitive performance
*p‑tau↓,
*cognitive↑,
*memory↑, prevented Acetylcholinesterase activity from elevation as well as improved acetylcholine levels, and improved learning, and memory deficits via increased ERK1/2 and Akt phosphorylation
*ERK↑,
*p‑Akt↑,
*PPARγ↑, honokiol has been reported to elevate PPARγ levels in APPswe/PS1dE9 mice as PPARγ is related to ani-inflammatory
*PGC-1α↑, honokiol boosted the expression of PGC1α and PPARγ
*MMP↑, as well as reduced elevated mitochondrial membrane potential and mitochondrial ROS
*mt-ROS↓,
*SIRT3↑, Honokiol has been found as a dual SIRT-3 activator and PPAR-γ agonist that reduced oxidative stress markers within cells and changed the AMPK pathway
*IL1β↓, honokiol prevented restraint stress-induced cognitive dysfunction by reducing the hippocampus's production of IL-1β, TNF-α, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)
*TNF-α↓,
*GRP78/BiP↓,
*CHOP↓,
*NF-kB↓, Additionally, the neuroprotective benefits of honokiol in mice with Aβ-induced learning and memory impairment have been attributed to the inactivation of NF-κB
*GSK‐3β↓, Treatment of honokiol in PC12 cells resulted in reduced GSK-3β and induced β-catenin which effectively showed the neuroprotective and anti-oxidant effect in AD therapy
*β-catenin/ZEB1↑,
*Ca+2↓, , anti-apoptotic effect via reduced caspase 3 levels, and protected membrane injury by reduced calcium level has been investigated in PC12 cells of AD models
*AChE↓, protective effects by serving as an antioxidant, reduced AchE levels, repaired neurofibrillary tangles, reduced NF-kB which downregulates Aβ plaque
*SOD↑, fig1
*Catalase↑,
*GPx↑,

2887-

HNK,

Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming

in-vitro,

AD,

BV2

*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
*ATP↑,
*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
*MMP↑,
*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
*PGC-1α↑,

2894-

HNK,

Pharmacological features, health benefits and clinical implications of honokiol

Review,

Var,

Review,

AD,

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

2643-

MCT,

Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism

Review,

Nor,

*Akt↑, increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway.
*AMPK↓,
*TGF-β↓, MCT downregulates TGF-β signaling
eff↑, beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.
*BioEnh↑, Furthermore, addition of the combination of chilli and MCT to meals increased diet-induced thermogenesis by over 50% in heathy normal-weight humans
*ATP↑, a key regulator of energy metabolism and mitochondrial membrane ATP synthase (ATP5α) were significantly upregulated by MCT.
*PGC-1α↑, also observed a significant increase in protein level of PGC-1α and ATP5α
*p‑mTOR↑, increased levels in both total and phosphorylated Akt and mTOR
*SMAD3↓, a compensatory response of the huge reduction in Smad3.

2248-

MF,

Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc-1α expression: Follow-up to an in vitro magnetic mitohormetic study

in-vivo,

Nor,

1.5 mT, 10 min/week

mice

*PGC-1α↑, The combination of PEMFs and exercise for 6 weeks enhanced running performance and upregulated muscular and adipose Pgc-1α transcript levels, whereas exercise alone was incapable of elevating Pgc-1α levels.
*GutMicro↑, The gut microbiome Firmicutes/Bacteroidetes ratio decreased with exercise and PEMF exposure, alone or in combination, which has been associated in published studies with an increase in lean body mass.
*FAO↓, >4 months PEMF treatment alone enhanced oxidative muscle expression, fatty acid oxidation, and reduced insulin levels.
*Insulin↓,

2247-

MF,

Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis

in-vivo,

Nor,

Sprague Dawley rats

*Glycolysis↓, PEMF-treated animals exhibited decreased glycolysis and increased LDHB expression, enhancing NAD signaling and ATP production
*LDHB↑,
*NAD↑,
*ATP↑,
*antiOx↑, Antioxidant protein levels increased, controlling ROS production.
*ROS↑,
*YAP/TEAD↑, upregulation of YAP and PGC1alpha and increasing slow myosin isoforms, thus speeding up physiological recovery.
*PGC-1α↑,
*TCA↑, increased in PEMF-treated injured limbs
*FAO↑,
*OXPHOS↑, Oxidative phosphorylation was increased in the muscle of injured rats that underwent PEMF treatment

2260-

MF,

Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming

in-vitro,

GBM,

U87MG

18 mT at the center

in-vitro,

GBM,

LN229

in-vivo,

NA,

AMF for 30 min daily, for a total of five sessions.

mice

TumCP↓, proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz.
TumCG↓, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival
OS↑,
ROS↑, This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression.
SOD2↑,
eff↓, anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger.
ECAR↓, decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR).
OCR↑,
selectivity↑, This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Furthermore, in cancer cells, AMF decreased ECAR and increased OCR, while there were no changes in normal cells.
*toxicity∅, did not affect non-cancerous human cells [normal human astrocyte (NHA), human cardiac fibroblast (HCF), human umbilical vein endothelial cells (HUVEC)].
TumVol↓, The results showed a significant treatment effect, as assessed by tumor volume, after conducting AMF treatment five times a week for 2 weeks
PGC-1α↑, Corresponding to the rise in ROS, there was also a time-dependent increase in PGC1α protein expression post-AMF exposure
OXPHOS↑, enhancing mitochondrial oxidative phosphorylation (OXPHOS), leading to increased ROS production
Glycolysis↓, metabolic mode of cancer cells to shift from glycolysis, characteristic of cancer cells, toward OXPHOS, which is more typical of normal cells.
PKM2↓, We extracted proteins that changed commonly in U87 and LN229 cells. Among the individual proteins related to metabolism, pyruvate kinase M2 (PKM2) was found to be inhibited in both.

5604-

NaHCO3,

Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity

vitro+vivo,

Melanoma,

B16-BL6

Six-week-old female BALB/c mice and C57BL/6 J mice

in-vitro,

BC,

4T1

eff↑, identified sodium bicarbonate (NaBi) as the potent metabolic reprogramming agent that enhanced antitumor responses in the acidic TME.
eff↑, NaBi and oAd-αCD47 therapy significantly inhibited tumor growth and produced complete immune control in various tumor-bearing mouse models.
TumMeta↓, suggesting its potential as an effective neoadjuvant treatment for preventing postoperative tumor recurrence and metastasis.
pH↑, NaBi improves the acidity of the TME and activates the CaMKII/CREB/PGC1α mitochondrial biosynthesis signaling pathway
CaMKII ↑,
CREB↑,
PGC-1α↑, NaBi increases the mitochondrial content of T cells and BMDMs by promoting the expression of PGC1α mediated by the Ca2+-CaMKII-CREB signaling pathway in an LA environment
AntiTum↑, oral NaBi enhances the antitumor effect of oAd-αCD47.
Imm↑, We proposed that sodium bicarbonate (NaBi) can act as an immunomodulator to reprogram metabolic disorders of CD8+ T cells and TAMs in an acidic environment.
CD8+↑, Combination therapy remodels the immunosuppressive microenvironment to promote activation of CD8+ T cells and TAMs
TAMS↑,

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↓,

5781-

RES,

Resveratrol improves health and survival of mice on a high-calorie diet

in-vivo,

Nor,

mice

*AntiAge↑, Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK)
*IGF-1↓,
*AMPK↑,
*CRM↑, resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways.
*PGC-1α↑, activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function.
*mtDam↓,
*motorD↑, Surprisingly, the resveratrol-fed HC mice steadily improved their motor skills as they aged
*hepatoP↑, At 18 months of age it was apparent that the high-calorie diet greatly increased the size and weight of livers and that resveratrol prevented these changes
*Dose↝, this study shows that an orally available small molecule at doses achievable in humans can safely reduce many of the negative consequences of excess caloric intake, with an overall improvement in health and survival.

5788-

RES,

Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans

Trial,

Nor,

11 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days.

*AMPK↑, In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels,
*SIRT1↑, Resveratrol, which was discovered in a small-molecule screen as a potent SIRT1 activator
*PGC-1α↑,
*BP↓, Systolic blood pressure dropped and HOMA index improved after resveratrol.
*CRM↑, 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.
*Dose↝, resveratrol (150 mg/day (99%); resVida™)
*mtDam↓, Resveratrol increases AMPK activity, increases mitochondrial efficiency and respiration on fatty acid substrates.
*ALAT↓, paralleled by lower plasma ALAT values, as mentioned before, both indicating improved liver function.
*hepatoP↑,

2566-

RES,

A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke

Review,

Stroke,

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

2472-

RES,

Resveratrol Restores Sirtuin 1 (SIRT1) Activity and Pyruvate Dehydrogenase Kinase 1 (PDK1) Expression after Hemorrhagic Injury in a Rat Model

in-vivo,

Nor,

rat

*SIRT1↑, However, resveratrol treatment along with resuscitation fluid restored SIRT1 activity.
*PGC-1α↑, When resveratrol was administered 10 min after the start of resuscitation, the protein level of SIRT1, PGC-1α and c-Myc in the nuclear fraction was restored.
*cMyc↑,
*PDK1↓, The experiments demonstrated a significant increase in PDK1 after T-H, which was abolished by resveratrol treatment

3790-

UA,

Therapeutic applications of ursolic acid: a comprehensive review and utilization of predictive tools

*Inflam↓, anti-inflammatory, antioxidant, anticancer, antidiabetic, antimicrobial, antihyperlipidemic, anti-obesity, neuroprotective, hepatoprotective, and cardioprotective activities.
*antiOx↑,
AntiCan↑,
*neuroP↑,
*hepatoP↑,
*cardioP↑,
*MMP↑, UA supports mitochondrial function by enhancing mitochondrial membrane potential, reducing ROS production, and promoting mitochondrial biogenesis through PGC-1α activation.
*ROS↓,
*PGC-1α↑,
*BDNF↑, UA has been shown to upregulate the expression of BDNF, which supports synaptic plasticity and enhances cognitive functions.
*cognitive↑,
Bcl-2↓, UA has been shown to decrease CCAAT/enhancer-binding protein β and Bcl-2 levels, while raising cytoplasmic cytochrome C levels
Cyt‑c↑,
DR5↑, UA induces extrinsic apoptosis by increasing death receptor 5 (DR5) expression and activating caspase 9, 8, and 3
Casp9↑,
Casp8↑,
Casp3↑,
TumCCA↑, UA’s anticancer properties is its capacity to cause cell cycle arrest.
*BioAv↓, its clinical applicability is limited by its poor solubility (1.02 × 10–4 mg/L at 25 °C) and bioavailability
*Dose↝, a study indicated that only 4 out of 14 subjects had detectable UA levels after a 100 mg dose; however, this number increased to 9 out of 14 when the dose was raised to 1000 mg.
*Half-Life↓, The rapid elimination of UA from the body further complicates its pharmacokinetics, necessitating alternative delivery methods to enhance its bioavailability
*Half-Life↓, The half-life of UA varies among species; for example, studies in rats have reported a half-life of approximately 4.3 h following oral administration

4864-

Uro,

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease

Review,

AD,

*neuroP↑, urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy.
*Half-Life↝, Urolithins appear in the human circulation within a few hours of consumption of ET-containing foods, reaching maximum concentrations after 24–48 h and complete excretion in urine/faeces within 72 h.
*BBB↑, urolithins can permeate the blood–brain barrier (BBB)
*toxicity↓, Urolithins are relatively non-toxic, as shown by studies in rats. The lethal dose 50 (LD50) has been found to be greater than 5 g/kg body weight in rat
*Inflam↓, In a study of Fisher rats [185], urolithin A was found to be the most effective anti-inflammatory compound derived from pomegranate consumption.
*Strength↑, Another clinical trial has shown that UA at doses of 500 mg and 1,000 mg for 4 weeks modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elders [
*BACE↓, There is evidence suggesting that these molecules inhibit BACE1 activity, leading to reduced Aβ production.
*Aβ↓,
*MitoP↑, Urolithin A May Trigger Mitophagy
*SIRT1↑, Activation of SIRT1/3, AMPK, PGC1-α and Inhibition of mTOR1
*SIRT3↑,
*AMPK↑,
*PGC-1α↑,
*mTOR↓,
*PARK2↑, urolithin A (1000 mg) has been shown to transcriptionally increase Parkin and BECN1 levels after 28 days of treatment in humans
*Beclin-1↑,
*ROS↓, by their actions to reduce BACE1 activity, Aβ fibrillation, ROS damage, inflammation
*GutMicro↑, impact on the microbiome may be an additional contribution to reducing AD risk
*Risk↓,

4311-

VitB1/Thiamine,

Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy

in-vivo,

AD,

mouse model

*Aβ↓, Thiamine deficiency exacerbates amyloid beta (Aβ) deposition, tau hyperphosphorylation and oxidative stress.
*p‑tau↓, BFT activates the Nrf2/ARE pathway and is a promising therapeutic agent for the treatment of diseases with tau pathology, such as AD
*ROS↓,
*cognitive↑, Benfotiamine (BFT) rescued cognitive deficits and reduced Aβ burden in amyloid precursor protein (APP)/PS1 mice.
*OS↑, Chronic dietary treatment with BFT increased lifespan, improved behavior, reduced glycated tau, decreased NFTs and prevented death of motor neurons.
*Mood↑,
*neuroP↑,
*Inflam↓, BFT administration significantly ameliorated mitochondrial dysfunction and attenuated oxidative damage and inflammation.
*NRF2↑, BFT and its metabolites (but not thiamine) trigger the expression of Nrf2/antioxidant response element (ARE)-dependent genes in mouse brain
*PGC-1α↑, BFT administration resulted in an upregulation of PGC-1α mRNA levels in P301S TG mice
*AGEs↓, BFT treatment reduced advanced glycation end products
*4-HNE↓, BFT administration led to a significant reduction in the fluorescence signal for both 3-NT and 4-HNE
*NQO1↑, Exposure to BFT upregulated the mRNA levels of NQO1 in TG mice
*COX2↓, Our findings showed that BFT treatment induced a significant decrease in COX-2 (Fig. 7E, P < 0.05), TNF-α (Fig. 7F, P < 0.05), IL-1β (Fig. 7H, P < 0.05), and NF-κB p65
*TNF-α↓,
*IL1β↓,
*NF-kB↓,
*GSK‐3β↓, Exposure to BFT improves cognitive impairment and reduces the amyloid burden in APP/PS1 TG mice in a dose-dependent fashion and was reported to diminish tau phosphorylation, which was attributed to decreased GSK-3β activity (26).

4034-

VitB3,

Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models

in-vivo,

AD,

*cognitive↑, dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex;
*NAD↑, Evidence shows that NR treatment increases intracellular NAD+ concentration and improves NAD+-dependent activities in the cell
*BACE↓, BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos
*Aβ↓, thus preventing Aβ production in the brain.
*PGC-1α↑, NR might reduce the Aβ burden in AD brain via enhancing PGC-1α expression, which increases BACE1 ubiquitination, degradation, and improves mitochondrial metabolism

Showing Research Papers: 1 to 27 of 27

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 3,
Total Targets: 75

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

4-HNE↓, 2, antiOx↑, 6, Catalase↑, 1, Ferroptosis↓, 1, GPx↑, 1, GSH↑, 1, H2O2↓, 1, HK1↑, 1, HO-1↑, 3, Keap1↑, 1, lipid-P↓, 1, mt-lipid-P↓, 1, MDA↓, 1, Mets↝, 1, MPO↓, 1, NQO1↑, 2, NRF2↑, 7, OXPHOS↑, 2, PARK2↑, 1, ROS↓, 11, ROS↑, 1, mt-ROS↓, 1, SIRT3↑, 4, SOD↑, 1, Thiols↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 5, Insulin↓, 2, MMP↑, 5, mtDam↓, 2, PGC-1α↑, 22,

Core Metabolism/Glycolysis ⓘ

adiP↑, 1, ALAT↓, 2, AMPK↓, 1, AMPK↑, 5, cMyc↑, 1, CRM↑, 2, FAO↓, 2, FAO↑, 1, glucose↓, 1, GlucoseCon↑, 1, Glycolysis↓, 1, Glycolysis↑, 2, LDHB↑, 1, NAD↑, 2, NADH:NAD↑, 1, PDK1↓, 1, PKM2↑, 1, PPARα↑, 2, PPARγ↑, 4, SIRT1↑, 6, TCA↑, 1,

Cell Death ⓘ

Akt↑, 1, p‑Akt↑, 1, Apoptosis↓, 2, Casp3↓, 2, Cyt‑c↑, 1, Cyt‑c∅, 1, Ferroptosis↓, 1, YAP/TEAD↑, 1,

Transcription & Epigenetics ⓘ

Ach↑, 2,

Protein Folding & ER Stress ⓘ

CHOP↓, 1, GRP78/BiP↓, 1, HSP70/HSPA5↝, 1,

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1, MitoP↑, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1, ERK↑, 1, FOXO↑, 1, GSK‐3β↓, 3, IGF-1↓, 1, mTOR↓, 2, p‑mTOR↑, 1,

Migration ⓘ

AntiAg↑, 2, Ca+2↓, 2, MMP9↓, 1, NFAT↓, 1, Rho↓, 1, SMAD3↓, 1, TGF-β↓, 1, β-catenin/ZEB1↑, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1, VEGF↑, 1,

Barriers & Transport ⓘ

BBB↓, 1, BBB↑, 4, GLUT3↑, 1, GLUT4↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1↓, 1, IL1β↓, 4, IL6↓, 1, Inflam↓, 8, NF-kB↓, 5, p65↓, 1, TLR4↓, 1, TNF-α↓, 7,

Synaptic & Neurotransmission ⓘ

AChE↓, 2, BDNF↑, 2, MAOA↝, 1, tau↓, 1, p‑tau↓, 2,

Protein Aggregation ⓘ

AGEs↓, 1, Aβ↓, 6, BACE↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 3, BioAv↑, 1, BioEnh↑, 1, Dose↝, 3, eff↑, 7, Half-Life↓, 2, Half-Life↝, 2,

Clinical Biomarkers ⓘ

ALAT↓, 2, AST↓, 1, BP↓, 2, GutMicro↑, 2, IL6↓, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, cardioP↑, 2, cognitive↑, 8, hepatoP↑, 4, memory↑, 3, Mood↑, 1, motorD↑, 5, neuroP↑, 10, OS↑, 2, Risk↓, 1, Strength↑, 1, toxicity↓, 1, toxicity∅, 2,
Total Targets: 128

Scientific Paper Hit Count for: PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

5 Honokiol
4 Hydrogen Gas
4 Resveratrol
3 Magnetic Fields
1 Alpha-Lipoic-Acid
1 Crocetin
1 diet Short Term Fasting
1 EGCG (Epigallocatechin Gallate)
1 MCToil
1 Bicarbonate(Sodium)
1 Quercetin
1 Ursolic acid
1 Urolithin
1 Vitamin B1/Thiamine
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#:927  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

PGC-1α Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

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 ⓘ

Autophagy & Lysosomes ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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