MMP Cancer Research Results

MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱

Source:

Type:

Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.

Scientific Papers found: Click to Expand⟱

4389-

AgNPs,

Graphene Oxide-Silver Nanocomposite Enhances Cytotoxic and Apoptotic Potential of Salinomycin in Human Ovarian Cancer Stem Cells (OvCSCs): A Novel Approach for Cancer Therapy

in-vitro,

Ovarian,

tumCV↓, Ag was toxic to OvCSCs and reduced cell viability by mediating the generation of reactive oxygen species, leakage of lactate dehydrogenase, reduced mitochondrial membrane potential
ROS↑,
LDH↓,
MMP↑,
CSCs↓, rGO–Ag may be a novel nano-therapeutic molecule for specific targeting of highly tumorigenic ALDH+CD133+ cells
AntiCan↑, Overall, these results suggest that the rGO–Ag is a promising material for inhibiting the cell viability of ovarian cancer cells and ovarian cancer stem cells.

4436-

AgNPs,

Silver Nanoparticles (AgNPs) as Enhancers of Everolimus and Radiotherapy Sensitivity on Clear Cell Renal Cell Carcinoma

in-vitro,

Kidney,

786-O

61 ± 10 nm

AgNP doses ranging from 500 to 3000 µg/mL for 24 h

ROS↑, AgNPs are cytotoxic to 786-O cells, a ccRCC cell line, entering through endocytosis, increasing ROS, depolarizing mitochondrial membrane, and blocking the cell cycle, leading to a reduction of proliferation capacity and apoptosis.
MMP↑,
TumCCA↑,
TumCP↓,
Apoptosis↑,
RadioS↑, 786-O is intrinsically resistant to radiation, but after AgNPs’ administration, radiation induces cytotoxicity through mitochondrial membrane depolarization and S phase blockage.

3448-

ALA,

Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line

*Inflam↓, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1, but its action on the values was decreased by the ALA treatment.
*ROS↓,
*GSH↑, through upregulation thiol redox system members [glutathione (GSH) and glutathione peroxidase (GSH-Px)] and down-regulation of mitochondrial ROS and extracellular productions.
*GPx↑,
*Casp3↓, HYPOX-induced caspase 3 and 9 activities were decreased by the ALA treatment
*Casp9↓,
*MMP↑, ALA treatment decreased HYPOX-induced mitochondrial membrane depolarization (JC-1) and intracellular ROS production levels

3447-

ALA,

Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells

in-vitro,

AD,

SH-SY5Y

*ATP↑, Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells.
*MMP↑, MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells.
*ROS↓, ROS levels were significantly lower in both cell lines treated with ALA.
*GlucoseCon↑, benefits to diabetic neuropathy and impaired glucose uptake, and the regeneration of glutathione (GSH) and vitamins C and E
*GSH↑,
*neuroP↑, ALA seems to have a positive effect on neurodegenerative diseases such as AD
*cognitive↑, ALA improves cognitive performance and could be considered as a promising bioactive substance for AD by affecting multiple mechanisms such as:
*Ach↑, (1) impaired acetylcholine production;
*Inflam↓, (2) hydroxyl radical formation, ROS production, and neuroinflammation;
*Aβ↓, (3) impaired amyloid plaque formation;
OXPHOS↓, ALA has also been shown to restore the expression of OXPHOS complexes in HepG2 cells, ranging in a concentration between 0.5–2 mM

2593-

Api,

Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo

in-vivo,

BC,

4T1

4T1 xenograft tumor mouse model

TumCP↓, API suppresses 4T1 cells proliferation
TumCMig↓, API restraints 4T1 cells migration and invasion
TumCI↓,
Apoptosis↑, API triggers 4T1 apoptosis and modulates the expression levels of apoptotic-associated proteins in 4T1 cells
MMP↑, API triggers the depolarization of ΔΨm in 4T1 cells
ROS↑, API induces ROS generation
p‑PI3K↓, The results revealed a significant downregulation of p-PI3K/PI3K, p-AKT/AKT, and Nrf2 in 4T1 cells following API treatment
PI3K↓,
Akt↓,
NRF2↓,
AntiTum↑, API exhibits anti-tumor activity in mice
OS↑, results of animal survival experiments show that API can appropriately prolong the survival of mice with mammary gland tumors

4813-

ASTX,

Astaxanthin Prevents Oxidative Damage and Cell Apoptosis Under Oxidative Stress Involving the Restoration of Mitochondrial Function

in-vitro,

AD,

*antiOx↑, Astaxanthin (ASTA), a natural compound known for its potent antioxidant properties, shows the biological activities in anti-apoptosis and antitumor.
*Apoptosis↓,
*AntiTum↑,
*ROS↓, ASTA significantly reduced H2O2-induced mitochondrial dysfunctions and restored the intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and respiratory capacity.
*MMP↑, Astaxanthin depresses oxidative stress-induced depolarization of mitochondrial membrane potential and restores the mitochondrial respiratory capacity.
*neuroP↑, Oxidative stress (OS) is one of the factors that result in cell damage and the development of neurological diseases such as Alzheimer's disease (AD).

2624-

Ba,

Baicalein inhibition of hydrogen peroxide-induced apoptosis via ROS-dependent heme oxygenase 1 gene expression

in-vitro,

Nor,

RAW264.7

*HO-1↑, In the present study, baicalein (BE) but not its glycoside, baicalin (BI), induced heme oxygenase-1 (HO-1) gene expression at both the mRNA and protein levels
*ERK↑, BE induction of HO-1 gene expression via activation of ERKs in macrophages
*ROS↓, HO-1 protein indeed participates in BE's protection against H2O2-induced cytotoxicity via reducing ROS production
*eff↑, BE, but not BI, protection of RAW264.7 cells from H2O2-induced apoptosis
*MMP↑, BE inhibits H2O2-induced reduction of the mitochondrial membrane potential in RAW264.7 cell
*Cyt‑c∅, the release of cytochrome c from mitochondria to the cytosol was detected in H2O2-treated macrophages, and this was blocked by the addition of BE but not BI.

2623-

Ba,

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells

in-vitro,

Nor,

HEI193

50 and 100 μM

*DNAdam↓, Our results showed that baicalein effectively inhibited H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation.
*ROS↓,
*Bax:Bcl2↓, increased the Bax/Bcl-2 ratio
*p‑NRF2↑, baicalein increased not only the expression but also the phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and promoted the expression of heme oxygenase-1 (HO-1)
*HO-1↑, it is well known that the antioxidant efficacy of baicalein is related to the activation of the Nrf2/HO-1 signaling pathway
*neuroP↑, suggested that baicalein may have a beneficial effect on the prevention and treatment of peripheral neuropathy induced by oxidative stress.
*MMP↑, inhibitory effect of baicalein on MMP reduction

2605-

Ba,

BA,

Potential therapeutic effects of baicalin and baicalein

Review,

Var,

Review,

Stroke,

Review,

IBD,

Review,

Arthritis,

Review,

AD,

Review,

Park,

cardioP↑, cardioprotective activities.
Inflam↓, Decreasing the accumulation of inflammatory mediators and improving cognitive function
cognitive↑,
*hepatoP↑, Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms
*ROS?, Reducing oxidative stress and protecting the mitochondria to inhibit apoptosis are proposed as hepatoprotective mechanisms of baicalin in NAFLD
*SOD↑, Baicalin could reduce the levels of ROS and fatty acid-induced MDA, and increase superoxide dismutase (SOD) and glutathione amounts compared to the control.
*GSH↑,
*MMP↑, Moreover, baicalin could partially restore mitochondrial morphology and increase ATP5A expression and mitochondrial membrane potential (Gao et al., 2022).
*GutMicro↑, After baicalein treatment, a remodelling in the overall structure of the gut microbiota was observed
ChemoSen↑, Besides, a combination of baicalin and doxorubicin could elevate the chemosensitivity of MCF-7 and MDA-MB-231 breast cancer cells
*TNF-α↓, Baicalin can protect cardiomyocytes from hypoxia/reoxygenation injury by elevating the SOD activity and anti-inflammatory responses through reducing TNF-α, enhancing IL-10 levels, decreasing IL-6, and inhibiting the translocation of NF-κB to the nucl
*IL10↑,
*IL6↓,
*eff↑, Studies show that baicalin and baicalein may be effective against IBD by suppressing oxidative stress and inflammation, and regulating the immune system.
*ROS↓,
*COX2↓, baicalein can improve the symptoms of ulcerative colitis by lowering the expression of pregnane X receptor (PXR), (iNOS), (COX-2), and caudal-type homeobox 2 (Cdx2), as well as the NF-κβ and STAT3
*NF-kB↓,
*STAT3↓,
*PGE2↓, Administration of baicalin (30-90 mg/kg) could decrease the levels of prostaglandin E2 (PEG2), myeloperoxidase (MPO), IL-1β, TNF-α, and the apoptosis-related genes including Bcl-2 and caspase-9
*MPO↓,
*IL1β↓,
*MMP2↓, Rheumatoid arthritis RA mouse model by supressing relevant proinflammatory cytokines such as IL-1b, IL-6, MMP-2, MMP-9, TNF-α, iNOS, and COX-2)
*MMP9↓,
*β-Amyloid↓, Alzheimer’s disease (AD) : reduce β-amyloid and trigger non-amyloidogenic amyloid precursor proteins.
*neuroP↑, For instance, administration of baicalin orally for 14 days (100 mg/kg body weight) exhibited neuroprotective effects on pathological changes and behavioral deficits of Aβ 1–42 protein-induced AD in vivo.
*Dose↝, administration of baicalin (500 mg/day, orally for 12 weeks) could improve the levels of total cholesterol, TGs, LDLC and apolipoproteins (APOs), and high-sensitivity C-reactive protein (hs-CRP) in patients with rheumatoid arthritis and coronary arte
*BioAv↝, the total absorption of baicalin depends on the activity of intestinal bacteria to convert baicalin to baicalein as the first step.
*BioAv↝, Kidneys, liver, and lungs are the main organs in which baicalin accumulates the most.
*BBB↑, Baicalin and baicalein can pass through the blood brain barrier (BBB)
*BDNF↑, mechanism of action for baicalein is illustrated in Figure 3. Activation of the BDNF/TrkB/CREB pathway, inhibition of NLRP3/Caspase-1/GSDMD pathway,

3505-

Bor,

Mineral requirements for mitochondrial function: A connection to redox balance and cellular differentiation

Review,

NA,

*glucose↓, Boron supplementation in human subjects decreased serum glucose, creatinine, and calcitonin,
*creat↓,
*SOD↑, while it increased serum triglycerides, ceruloplasmin, and erythrocyte superoxide dismutase
*MMP↑, Boron administration had positive effects on mitochondrial membrane potential and function in multiple species, but entry into mitochondria was not confirmed
*ROS↓, The available evidence suggest that mitochondria may benefit from the availability of boron, which may promote metabolism and reduce redox stress.

3507-

Bor,

Boron inhibits apoptosis in hyperapoptosis condition: Acts by stabilizing the mitochondrial membrane and inhibiting matrix remodeling

*MMP↑, n the presence of boron, there was a significant and dose-dependent increase in MMP, which inhibited mitochondrial remodeling to the condensed state and hence the release of Cyt c and initiation of apoptosis.
*Cyt‑c↓, Boron inhibits the release of mitochondrial Cyt c and activation of Casp
*Apoptosis↓, Boron inhibits apoptosis.
*Casp3↓,
*NO↓, Nitric oxide (NO) and iNOS levels decrease in boron treated hyperapoptosis cultures.
*iNOS↓,

760-

Bor,

Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer’s Disease

in-vivo,

AD,

rats

*memory↑, BA reduced damage to learning and memory functions and significantly lowered oxidative stress markers in the AD model.
*ROS↓, been reported that BA also reduces oxidative stress by increasing glutathione reserves,
*GSH↑,
*Aβ↓, and strongly inhibits Aβ aggregation via hydroxyl group
*Inflam↓, BA can act as a protective agent in apoptotic processes by regulating oxidative and inflammatory processes as well as mitochondrial membrane potential
*MMP↑,
*lipid-P↓, BA added to the diet prevented lipid peroxidation by supporting and strengthening the antioxidant defense system.
*Ca+2↓, Boron is thought to prevent apoptosis and strengthen antioxidant defense by reducing intracellular oxygen radicals and calcium levels.
*cognitive↑, Our hypothesis is that boric acid can improve cognitive function and histopathological outcomes by reducing oxidative stress in rats with STZ-induced Alzheimer’s Disease
*TOS↓, After BA administration, it increased TAS by increasing the antioxidant effect, and as a result, TOS and OSI decreased.

5830-

CAP,

Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro

in-vitro,

Nor,

HK-2

*IL1β↓, capsaicin ameliorated LPS-induced cytotoxicity in vitro and attenuated the release of interleukin (IL)-1β and IL-18.
*IL18↓,
*TRPV1↑, Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 –mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis
*ROS↓, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis.
*MMP↑,
*Apoptosis↓,
*RenoP↑, These findings suggest that capsaicin shows a protective effect in in vitro acute kidney injury model.
*Inflam↓, Capsaicin ameliorates LPS-induced cytotoxicity and inflammation response in HK-2 cells
*UCPs↑, Capsaicin alleviates LPS-induced pyroptosis in HK-2 cells by activating TRPV1/UCP2 axis

5198-

CAP,

Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines

in-vitro,

CRC,

LoVo

in-vitro,

CRC,

Colo320

tumCV↓, Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells.
DNAdam↑, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death
Apoptosis↑, We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential.
ROS↑,
MMP↑,
Casp3↑, capsaicin induced a dramatic increase in caspase 3 activity
chemoPv↑, it may be a beneficial agent for colon cancer treatment and chemoprevention.

2652-

CAP,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, capsaicin has been reported as both a chemopreventive and as an anticancer agent
AntiCan↑,
ROS↑, Capsaicin has been reported to induce ROS-dependent cell death in various cancers, including colorectal [63], prostate [64,65], bladder [66,67,68], and pancreatic [69,70] cancers.
TumCG↓, reported to inhibit tumor growth in vivo in mouse xenograft models of prostate [64] and bladder [66] cancers.
ROS↑, Mechanistically, capsaicin-mediated ROS accumulation
MMP↑, leads to mitochondrial membrane depolarization [63,64,66],
Apoptosis↑, which further triggers mitochondria-dependent apoptosis
TumCCA↑, as well as G0/G1 cell cycle arrest
JNK↑, in bladder cancer cells, capsaicin induces JNK activation in an ROS-dependent manner
SOD↓, (1) inhibition of the activity of antioxidant enzymes SOD, catalase (CAT), and glutathione peroxidase [70];
Catalase↓,
GPx↓,
other↓, (2) inhibition of the activity of mitochondrial complex-I and complex-III in the electron transport chain [70];
SIRT1↓, (3) downregulation of the expression of sirtuin-1, a NAD-dependent deacetylase that regulates the expression of various antioxidant enzymes [69];
NADPH↑, (4) upregulation of the expression of NADPH oxidase 4, which generates superoxide [69];
FOXO3↑, (5) increased expression of FOXO3a, which is a transcription factor that regulates the oxidative stress response [68].

5943-

Cela,

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Review,

Arthritis,

Review,

IBD,

Review,

AD,

Review,

Park,

*other↝, The most abundant and promising bioactive compound derived from the root of this plant is celastrol, also called tripterine, which possess a broad range of biological activities
*other↝, TW is generally used in the treatment of Crohn’s disease (CD) in China.
*CRP↓, Inflammatory parameters, including c-reactive protein (CRP), also decreased
*eff↝, Etanercept plus TW had an equivalent therapeutic effect to that of Etanercept plus MTX and were both well tolerated
*other↑, TW in human kidney transplantation (26). Rejection occurred in 4.1% of patients treated with TW versus 24.5% of control patients, showing efficacy in the prevention of renal allograph rejection
*CXCR4↓, celastrol decreases hypoxia-induced FLS invasion by inhibiting HIF-1α-mediated CXCR4 transcription
*IL1β↓, Authors have shown that it decreases the production of IL-1β, IL-6, IL-17, IL-18, and TNF by SIC cells harvested from arthritic rats
*IL6↓,
*IL17↓,
*IL18↓,
*TNF-α↓,
*MMP9↓, celastrol reduces MMP-9 production, which limits bone damage
*PGE2↓, celastrol suppresses LPS-induced expression of PEG2 via the downregulation of COX-1 and COX-2 activation
*COX1↓,
*COX2↓,
*PI3K↓, associated with a decrease in PI3K/Akt pathway
*Akt↓,
*other↑, Remarkably, this bone-protective property of celastrol in arthritic models is further supported by studies performed in cancer models
TumCCA↑, celastrol induces cell cycle arrest, apoptosis, and autophagy by the activation of reactive oxygen species (ROS)/c-Jun N-terminal kinases (JNK) signaling pathway
Apoptosis↑,
ROS↑,
JNK↑,
TumAuto↑, celastrol is still able to induce autophagy through HIF/BNIP3 activation
Hif1a↓, The inhibitory effect of celastrol on angiogenesis is mediated by the suppression of HIF-1α,
BNIP3↝,
HSP90↓, The inhibition of HSP90 by celastrol
Fas↑, activation of Fas/Fas ligand pathway in non-small-cell lung cancer
FasL↑,
ETC↓, inhibition of mitochondrial respiratory chain (MRC) complex I
VEGF↓, This inhibition of HIF-1α leads to the decrease of its target genes, such as the VEGF
angioG↓, Angiogenesis Inhibition
RadioS↑, celastrol can overcome tumor resistance to radiotherapy in prostate (129) and lung cancer cells
*neuroP↑, celastrol is a promising neuroprotective agent in animal models of neurodegenerative diseases, such as Parkinson disease (149), Huntington disease (149–151), Alzheimer disease
*HSP70/HSPA5↑, his induction of HSP70 by celastrol explains its beneficial effects not only in neurodegenerative disorders but also in inflammatory diseases.
*ROS↓, celastrol protects human dopaminergic cells from injury and apoptosis and prevents ROS generation and mitochondrial membrane potential loss
*MMP↑,
*Cyt‑c↓, It inhibits cytochrome c release, Bax/Bcl-2 alterations, caspase-9/3 activation, and p38 MAPK activation
*Casp3↓,
*Casp9↓,
*MAPK↓,
*Dose⇅, Authors discuss that it seems to have a narrow therapeutic window, and suggest that it may have a biphasic effect with protective properties at low concentrations and toxic effects at higher concentrations.
*HSPs↑, induces a set of HSPs (HSP27, 32, and 70) in rat cerebral cortical cultures, which are selectively impacted during the progression of this disease
BioAv↓, Due to this poor water solubility, celastrol has low bioavailability. oral administration of celastrol in rats results in ineffective absorption into the systemic circulation, with an absolute bioavailability of 17.06%
Dose↝, narrow therapeutic window of dose together with the occurrence of adverse effects. Our own data showed in vivo that the doses of 2.5 and 5 μg/g/day are effective and non-toxic in the treatment of arthritis in rats;

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

3831-

CUR,

Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease

Review,

AD,

*neuroP↑, Several studies have shown that C. longa is a potential neuroprotective drug
*ROS↓, Curcumin inhibited Aβ-induced DNA damage by reducing of ROS generation through p38 MAPK and AKT pathways
*Ca+2↓, attenuate apoptosis by regulating intracellular Ca2+ release, ROS, and mitochondrial membrane potential depolarization level in SH-SY5Y cells
*MMP↑,

3205-

EGCG,

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas

Review,

Var,

Review,

AD,

Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

1974-

EGCG,

Protective Effect of Epigallocatechin-3-Gallate in Hydrogen Peroxide-Induced Oxidative Damage in Chicken Lymphocytes

in-vitro,

Nor,

0, 22.5, 45, and 90 μM

*ROS↓, suppressed the increase in intracellular reactive oxygen species (ROS), nitric oxide (NO),
*NO↓,
*MMP↑, preincubation of the cells with EGCG increased mitochondrial membrane potential (MMP) and reduced calcium ion ([Ca2+]i) load.
*i-Ca+2↓, EGCC Increased Mitochondrial Membrane Potential and Decreased [Ca2+]i
*HO-1↑, expression of SOD, Heme oxygenase-1 (HO-1), Catalase (CAT), GSH-PX, nuclear factor erythroid 2-related factor 2 (Nrf2), and thioredoxin-1 (Trx-1).
*Catalase↑,
*NRF2↑,
*Trx1↑,
*antiOx↑, EGCC Increased Antioxidant Capacity
*SOD↑, EGCC Decreased ROS and Increased SOD Generation
*Apoptosis↓,

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.

3783-

FA,

Design, Synthesis, and Biological Evaluation of Ferulic Acid-Piperazine Derivatives Targeting Pathological Hallmarks of Alzheimer’s Disease

NA,

AD,

*ROS↓, developed 13a, harboring the key functional groups to provide not only symptomatic relief but also targeting oxidative stress, able to chelate iron, inhibiting NLRP3, and Aβ1–42 aggregation in various AD models.
*IronCh↑,
*NLRP3↓,
*Aβ↓,
*AChE↓, 13a exhibited promising anticholinesterase activity against AChE (IC50 = 0.59 ± 0.19 μM) and BChE (IC50 = 5.02 ± 0.14 μM) with excellent antioxidant properties
*BChE↓,
*antiOx↑,
*BBB↑, 13a turned out to be a promising molecule that can efficiently cross the blood–brain barrier.
*MMP↑, mitigated mitochondrial-induced reactive oxygen species and mitochondrial membrane potential damage triggered by LPS and ATP in HMC-3 cells.
*memory↑, 13a was found to be efficacious in reversing memory impairment in a scopolamine-induced AD mouse model in the in vivo studies.
*SOD↑, 13a notably modulates the levels of superoxide, catalase, and malondialdehyde along with AChE and BChE.
*Catalase↑,

3780-

FA,

Ferulic Acid: A Natural Antioxidant with Application Towards Neuroprotection Against Alzheimer’s Disease

Review,

AD,

*antiOx↑, natural source of antioxidants against AD.
*SOD↑, FA has been shown to restore the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and heme oxygenase-1 (HO-1).
*Catalase↑,
*HO-1↑,
*neuroP↑, neuroprotective role of FA through modulating the expression of several key proteins such as p38, Hsp70, ERK1/2, foxo3a and Akt
*AChE↓, Inhibition of acetylcholinesterase (AChE) activity and restoration of mitochondrial membrane potential by FA has also been reported.
*MMP↑,

3721-

Gb,

Ginkgo biloba Extract in Alzheimer’s Disease: From Action Mechanisms to Medical Practice

Review,

AD,

*antiOx↑, In addition to direct attenuation of ROS, EGb761 may also stabilize the cellular redox state by up-regulation of the protein level and activity of antioxidant enzymes
*ROS↓,
*SOD↑, increase the protein level and activity of superoxide dismutase (SOD) and catalase in rat hippocampus
*Catalase↑,
*GSR↑, (GSH) reductase and gamma-glutamylcysteinyl synthetase, two enzymes critical for reduction and synthesis of GSH, were also enhanced by EGb761
*MMP↑, EGb761 may maintain the integrity of the mitochondrial membrane; prevent cytochrome c release from the mitochondria,
*Inflam↓, EGb761 has been demonstrated to have anti-inflammatory effects
*Aβ↓, A number of recent reports indicate that EGb761 protects against Aβ-induced neurotoxicity by blockage of Aβ-induced events, such as ROS accumulation, glucose uptake, mitochondrial dysfunction, activation of AKT, JNK and ERK 1/2 pathways and apoptosis
*memory↑, after EGb761 treatment, Tg-2576 mice exhibited an enhancement of spatial learning and memory comparable to wild type mice [
*Dose↝, Nowadays, a daily dose of 240 mg has been extensively used to stabilize the disease progression in patients with AD
*BBB↑, EGb761 was able to cross the BBB effectively and retain its neuroprotective properties
*neuroP↑,

2071-

HNK,

Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient

Review,

Nor,

HaCaT

10 μg/ml

0.625 μg/ml was selected as the optimal concentration of M. officinalis extract since it was the lowest concentration that causes cell proliferation

*ROS↓, Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts.
*antiOx↑, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects.
*AntiAge↑, new approaches to anti–aging treatments
*MMP↑, increases MMP
*ECAR↓, senescent fibroblasts treated with M. officinalis extract had lower ECAR values than those treated with DMSO, suggesting that M. officinalis treatment lowed glycolysis rate
*Glycolysis↓, honokiol, similar to M. officinalis, reduced the dependence of glycolysis as an energy source, indicating restoration of mitochondrial function by honokiol.
*PAR-2↓, downregulation of PAR–2 expression by M. officinalis may reduce skin pigmentation.
*CXCL12↑, upregulation of SDF–1 expression by M. officinalis may reduce skin pigmentation.
*BMAL1↑, activation of Bmal–1 expression by M. officinalis promote skin turnover.
*mt-ROS↓, compared to M. officinalis extract, honokiol at 1 and 10 μM was more effective in lowering mitochondrial ROS levels
*OXPHOS↓, Inhibition of oxidative phosphorylation and induction of a compensatory shift toward glycolysis resulted in lower compensatory glycolysis in honokiol–treated senescent fibroblasts

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↓,

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↑,

2889-

HNK,

doxoR,

Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice

in-vivo,

Nor,

mice

*SIRT3↑, We have recently identified honokiol (HKL) as an activator of SIRT3
chemoP↑, HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin.
*cardioP↑, mice that received doxorubicin plus HKL showed preserved cardiac function, compared to doxorubicin and vehicle treated mice
mtDam↑, HKL-mediated activation of SIRT3 prevented Doxorubicin induced ROS production, mitochondrial damage and cell death in rat neonatal cardiomyocytes
ROS↑,
*ROS↓, We found that cells treated with HKL suppressed doxorubicin-induced ROS levels
*MMP↑, HKL preserves mitochondrial membrane potential.

2904-

LT,

Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons

in-vitro,

Park,

SK-N-SH

in-vitro,

AD,

*ROS↓, Food-derived compound luteolin possesses multitarget actions including reactive oxygen species (ROS)-scavenging activit
*neuroP↑, Upon the ROS-insulted primary neurons, luteolin concentration-dependently enhanced neuronal cell survival with efficacy higher than and potency similar to vitamin E.
*MMP↑, prevented the decreases in activities of mitochondria, catalase, and glutathione in ROS-insulted primary neurons
*Catalase↑, decreases of catalase/glutathione activity by H 2O 2 were markedly reversed following luteolin treatment.
*GSH↑,
selectivity↑, Results showed that luteolin mildly inhibited the viability of SK-N-SH cells (50% inhibition at 68.7 uM) and relatively strongly inhibited that of HuH-7 cells (50% inhibition at 14.3 uM), but did not affect that of primary neurons
*eff↑, luteolin can be designated as a potent neuroprotectant as well as suggesting that it may be effective either in the treatment of neurodegenerative diseases, such as cerebral ischemia, Parkinsons, and AD, or in the improvement of brain aging
*Cyt‑c↓, reduction of cytochrome c release from mitochondria into cytosome,

2916-

LT,

Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies

Review,

Var,

Review,

AD,

Review,

Park,

proCasp9↓, , by inactivating proteins; such as procaspase‐9, CDC2 and cyclin B or upregulation of caspase‐9 and caspase‐3, cytochrome C, cyclin A, CDK2, and APAF‐1, in turn inducing cell cycle
CDC2↓,
CycB/CCNB1↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1/CCNA1↑,
CDK2↓, inhibit CDK2 activity
APAF1↑,
TumCCA↑,
P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
VEGF↓,
Bcl-2↓,
Apoptosis↑,
p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
p‑EGFR↓,
p‑ERK↓,
p‑STAT3↓,
cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
SOD↓,
*BioAv↓, bioavailability of luteolin is very low. Due to the momentous first pass effect, only 4.10% was found to be available from dosage of 50 mg/kg intake of luteolin
*antiOx↑, luteolin classically exhibits antioxidant features
*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
*NO↓,
*GSTs↑, Luteolin may also have a role in protection and enhancement of endogenous antioxidants such as glutathione‐S‐transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
Akt↓,
CDK2↓, inhibit CDK2 activity
BNIP3↑, upregulation of BNIP3 gene
hTERT/TERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1↑, Activate beclin 1
TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
NF-kB↓,
IL1↓,
IL6↓,
EMT↓, Suppress EMT essentially notable in cancer metastasis
FAK↓, Block EGFR‐signaling pathway and FAK activity
E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
MDM2↓,
NOTCH↓, Inhibit NOTCH signaling
MAPK↑, Activate MAPK to inhibit tumor growt
Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
N-cadherin↓,
Snail↓,
MMP2↓, negatively regulated MMP2 and TWIST1
Twist↓,
MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
MMP↓,
*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
*MMP↑, Reverse mitochondrial membrane potential dissipation
*Aβ↓, Inhibit Aβ25‐35
*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
Trx1↑, luteolin against human bladder cancer cell line T24 was due to induction cell‐cycle arrest at G2/M, downregulation of p‐S6, suppression of cell survival, upregulation of p21 and TRX1, reduction in ROS levels.
ROS↓,
*NRF2↑, Luteolin reduced renal injury by inhibiting XO activity, modulating uric acid transporters, as well as activating Nrf2 HO‐1/NQO1 antioxidant pathways and renal SIRT1/6 cascade.
NRF2↓, Luteolin exerted anticancer effects in HT29 cells as it inhibits nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway
*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
GutMicro↑, Luteolin was also observed to modulate gut microbiota which reduce the number of tumors in case of colorectal cancer by enhancing the number of health‐related microbiota and reduced the microbiota related to inflammation

3263-

Lyco,

Lycopene protects against myocardial ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening

in-vitro,

Nor,

H9c2

in-vitro,

Stroke,

*Apoptosis↓, LP pretreatment significantly increased cell viability, reduced myocardial infarct size and decreased the apoptosis rate.
*MMP↑, decrease of ΔΨm were attenuated by LP and the expressions of cytochrome c, APAF-1, cleaved caspase-9 and cleaved caspase-3 were also decreased by LP
*Cyt‑c↓,
*APAF1↓,
*cl‑Casp9↓,
*cl‑Casp3↓,
*Bcl-2↑, LP treatment markedly increased Bcl-2 expression, decreased Bax expression and the Bax/Bcl-2 ratio.
*BAX↓,
cardioP↑, myocardial ischemia-reperfusion injury (MIRI). LP protects against MIRI by inhibiting MPTP opening, partly through the modulation of Bax and Bcl-2.

2242-

MF,

Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair

in-vitro,

Nor,

2.5G, 5G, 10G, 15G, and 20G

*MMP↑, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation.
*Diff↑,
*OXPHOS↑, effect was mediated via increased OxPhos activity
*BMD↑, EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization
ATP∅, higher mitochondrial OxPhos activity leads to higher ATP production, increased cellular activity leads to increased ATP consumption.

4147-

MF,

PEMFs Restore Mitochondrial and CREB/BDNF Signaling in Oxidatively Stressed PC12 Cells Targeting Neurodegeneration

in-vitro,

AD,

PC12

PC12 cells exposed to hydrogen peroxide (H2O2)

*ROS↓, PEMF treatment significantly counteracted H2O2- and Aβ-induced cytotoxicity by restoring cell viability, reducing reactive oxygen species production, and improving catalase activity.
*Catalase↑,
*MMP↑, PEMFs preserved the mitochondrial membrane potential and decreased caspase-3 activation and chromatin condensation
*Casp3↓,
*p‑ERK↓, Mechanistically, PEMFs inhibited ERK phosphorylation and enhanced cAMP levels, CREB phosphorylation, and BDNF expression
*cAMP↑,
*p‑CREB↑,
*BDNF↑,
*neuroP↑, PEMFs modulate multiple stress response systems, promoting neuroprotection under oxidative and amyloidogenic conditions.

538-

MF,

The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift

in-vitro,

BC,

MDA-MB-231

in-vitro,

Melanoma,

MSTO-211H

TumCG↓, did not affect the non-malignant counterpart.
Ca+2↑,
COX2↓,
ATP↑, (ATP5B) and mitochondrial transcription (MT-ATP6)
MMP↑, significant enhancement of mitochondrial membrane potential (ΔΨm)
ROS↑, demonstrated for the first time the association of ROS production with the stimulation of the mitochondrial metabolism triggered by the electromagnetic field
OXPHOS↑,
mitResp↑, Mitochondrial respiration is increased by ELF-EMF exposure

4568-

MF,

Extremely low-frequency pulses of faint magnetic field induce mitophagy to rejuvenate mitochondria

Study,

NA,

*ETC↓, We report that ELF-WMF efficiently suppresses the mitochondrial mass to 70% by inhibiting the mitochondrial ETC complex II, which subsequently induces mitophagy and rejuvenates mitochondria.
*OCR↑, We found that Opti-ELF-WMF increased both the OCR and mitochondrial membrane potential by approximately 40%
*MMP↑,
*ROS⇅, Opti-ELF-WMF most strongly decreased the level of mitochondrial superoxide at 1 h, mitochondrial mass at 3 h, and mitochondrial membrane potential at 6 h, and most strongly increased them at 12 h
*MMP⇅,

3839-

Moringa,

Nutritional Value of Moringa oleifera Lam. Leaf Powder Extracts and Their Neuroprotective Effects via Antioxidative and Mitochondrial Regulation

*eff↑, moringa methanol extracts had more phenolic content and higher antioxidant activity than acetone extracts.
*ROS↓, pretreatments with methanol extracts showed a protective effect against H2O2-induced oxidative damage through increasing cell viability and reducing free radicals.
*lipid-P↓, the extract decreased lipid peroxidation and enhanced glutathione levels and antioxidant enzyme activity.
*GSH↑,
*antiOx↑,
*Ca+2↓, Finally, moringa also prevented mitochondrial dysfunction by regulating calcium levels and increasing mitochondrial membrane potential.
*MMP↑,
*neuroP↑, Moringa oleifera as a neuroprotective agent could be beneficial to protect against oxidative stress and provide necessary nutrients for a healthy diet.
*BBB↑, Polyphenolic compounds can pass across blood-brain barrier
*Catalase↑, 53% for CAT, 51% for SOD and 65% for GPx compared to no extract cells (100%). However, pretreatments with moringa extracts reversed this impairment in the defensive system
*SOD↑,
GPx↑,

1677-

PBG,

Propolis Inhibits UVA-Induced Apoptosis of Human Keratinocyte HaCaT Cells by Scavenging ROS

in-vitro,

Nor,

HaCaT

5 and 10 μg/mL

*Dose∅, demonstrated that propolis (5 and 10 μg/mL)
*AP-1↓, significantly inhibited the apoptosis of HaCaT cells induced by UVA-irradiation.
*MMP↑, protective effect against loss of mitochondrial membrane potential induced by UVA-irradiaiton in HaCaT cells.
*Casp3↓, inhibited the expression of activated caspase-3 induced by UVA-irradiation.
*ROS↓, generation of ROS was markedly reduced in cells pretreated with propolis

2431-

QC,

The Protective Effect of Quercetin against the Cytotoxicity Induced by Fumonisin B1 in Sertoli Cells

in-vitro,

Nor,

TM4

*Apoptosis↓, 40 μM quercetin improved cell viability, reduced apoptosis, and preserved cell functions.
*ROS↓, Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1
*antiOx↓, enhanced the expression of antioxidant genes
*MMP↑, improved mitochondrial membrane potential.
*GPI↑, elevated the mRNA and protein expression of glycolysis-related genes, including (Gpi1), (Hk2), (Aldoa), (Pkm), lactate (Ldha) and (Pfkl)
*HK2↑,
*ALDOA↑,
*PKM1↑,
*LDHA↑,
*PFKL↑,

3336-

QC,

Neuroprotective Effects of Quercetin in Alzheimer’s Disease

Review,

AD,

*neuroP↑, Neuroprotection by quercetin has been reported in several in vitro studies
*lipid-P↓, It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation.
*antiOx↑, In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways.
*Aβ↓,
*Inflam↓,
*BBB↝, It also has low BBB penetrability, thus limiting its efficacy in combating neurodegenerative disorders.
*NF-kB↓, downregulating pro-inflammatory cytokines, such as NF-kB and iNOS, while stimulating neuronal regeneration
*iNOS↓,
*memory↑, Quercetin has shown therapeutic efficacy, improving learning, memory, and cognitive functions in AD
*cognitive↑,
*AChE↓, Quercetin administration resulted in the inhibition of AChE
*MMP↑, quercetin ameliorates mitochondrial dysfunction by restoring mitochondrial membrane potential, decreases ROS production, and restores ATP synthesis
*ROS↓,
*ATP↑,
*AMPK↑, It also increased the expression of AMP-activated protein kinase (AMPK), which is a key cell regulator of energy metabolism.
*NADPH↓, Activated AMPK can decrease ROS generation by inhibiting NADPH oxidase activity
*p‑tau↓, Inhibition of AβAggregation and Tau Phosphorylation

3363-

QC,

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation

in-vitro,

Nor,

HBMECs

 (0.1, 0.5, 1 μmol/L)

*Apoptosis↓, Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis.
*angioG↑,
*NRF2↑, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression.
*Keap1↓,
*ATF6↓,
*GRP78/BiP↓,
*CLDN5↑, quercetin could increase the expression of Claudin-5 and Zonula occludens-1.
*ZO-1↑,
*MMP↑, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis.
*BBB↑, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
*ROS↓, Quercetin Could Inhibit Oxidative Stress
*ER Stress↓, In our study, ER stress was activated by H/R, and the levels of ATF6 and GRP78 were increased. Quercetin at 1 μmol/L was able to significantly reduce the protein levels of both, inhibit ER stress, and protect HBMECs from H/R injury

3365-

QC,

Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways

in-vivo,

Sepsis,

*ER Stress↓, quercetin could inhibit the level of ER stress as evidenced by decreased mRNA expression of PDI, CHOP, GRP78, ATF6, PERK, IRE1α
*PDI↓,
*CHOP↓,
*GRP78/BiP↓,
*ATF6↓,
*PERK↓,
*IRE1↓,
*MMP↑, and improve mitochondrial function, as presented by increased MMP, SOD level and reduced production of ROS, MDA.
*SOD↑,
*ROS↓,
*MDA↓,
*SIRT1↑, quercetin upregulated SIRT1/AMPK mRNA expression.
*AMPK↑,
*Sepsis↓, quercetin could protect against sepsis-induced ALI by suppressing oxidative stress-mediated ER stress and mitochondrial dysfunction via induction of the SIRT1/AMPK pathways.

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

3099-

RES,

Resveratrol and cognitive decline: a clinician perspective

Review,

Nor,

NA,

AD,

*antiOx↑, In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes.
*ROS↓,
*cognitive↑,
*neuroP↑,
*SIRT1↑, By inducing SIRT1, resveratrol may promote neurite outgrowth and enhance neural plasticity in the hippocampal region
*AMPK↑, Resveratrol also induces neurogenesis and mitochondrial biogenesis by enhancing AMP-activated protein kinase (AMPK), which is known to stimulate neuronal differentiation and mitochondrial biogenesis in neurons.
*GPx↑, figure 1
*HO-1↑,
*GSK‐3β↑,
*COX2↓,
*PGE2↓, Resveratrol also inhibits pro-inflammatory enzyme (i.e., COX-1 and -2) expression, reduces NF-κB activation as well as PGE2, NO, and TNF-α production, and cytokine release
*NF-kB↓,
*NO↓,
*Casp3↓,
*MMP3↓,
*MMP9↓,
*MMP↑, resveratrol attenuated ROS production and mitochondrial membrane-potential disruption; moreover, it restored the normal levels of glutathione (GSH) depleted by Aβ1-42
*GSH↑,
*other↑, resveratrol significantly increased cerebral blood flow (CBF) in the frontal cortex of young healthy humans.
*BioAv↑, receiving 200 mg/day of resveratrol in a formulation with quercetin 320 mg [53], in order to increase its bioavailability,
*memory↑, Resveratrol supplementation induced retention of memory and improved the functional connectivity between the hippocampus and frontal, parietal, and occipital areas, compared with placebo
*GlutMet↑, Also, glucose metabolism was improved and this may account for some of the beneficial effects of resveratrol on neuronal function.
*BioAv↓, The main problems related to the therapeutic or preventive use of resveratrol are linked to its low oral bioavailability and its short half-life in serum
*Half-Life↓,
*toxicity∅, On the other hand, the tolerability and safety profile of resveratrol is very high

3003-

RosA,

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases

Review,

Var,

Review,

AD,

Review,

Park,

*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

3028-

RosA,

Network pharmacology mechanism of Rosmarinus officinalis L.(Rosemary) to improve cell viability and reduces apoptosis in treating Alzheimer’s disease

in-vitro,

AD,

HT22

in-vivo,

NA,

*Aβ↓, It was found that rosemary could reversed Aβ25–35 induced damage to mouse hippocampal neuron HT22 cells,
*Apoptosis↓, significantly improved the viability of damaged cells, and reduced apoptosis
*antiOx↑, main antioxidant compound in rosemary, carnosic acid, also has neuroprotective effects.
*neuroP↑,
*eff↑, main active carnosic acid, carnosol, rosmarinol, rosmadial, genkwanin, cirsimaritin, rosmarinic acid and caffeic acid in Rosmarinus officinalis L,
*IGF-1↑, rosemary could elevated expression of IGF1, MMP9 and decreased mRNA levels of SRC, MAPK14, compared with the control group.
*MMP9↑,
*Src↓,
*MAPK↓,
*MMP↑, Rosemary reduced Aβ-induced HT22 cell damage in AD models to enhance the mitochondrial membrane potential levels

3319-

SIL,

Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms

Review,

AD,

Review,

Park,

Review,

Stroke,

*neuroP↑, Silymarin can be used as a neuroprotective therapy against AD, PD and CI
*ROS↓, Silymarin prohibit oxidative stress, pathologic protein aggregation.
*Inflam↓, Silymarin inhibit neuroinflammation, apoptosis, and estrogenic receptor modulation.
*Apoptosis↓,
*BBB?, Silymarin, as a polyphenolic complex, can cross the blood-brain barrier (BBB)
*tau↓, inhibitory action of Silibinin on tau protein phosphorylation in the hippocampus and cortical region of the brain could describe an important neuro-protective effect against AD progression
*NF-kB↓, inhibiting the NF-ÎºB pathway leading to attenuating the activity of NF-ÎºB (
*IL1β↓, inhibition of inflammatory responses such as IL-1Î² and TNF-Î± mRNA gene
*TNF-α↓,
*IL4↓, enhance the production of IL-4 in the hippocampal region
*MAPK↓, down-regulation of MAPK activation
*memory↑, Silibinin exhibited its beneficial effect on improvement of memory impairment in rats
*cognitive↑, Silymarin was able to alleviated the impairment in cognitive, learning and memory ability caused by AÎ² aggravation through making a reduction in oxidative stress in the hippocampal region
*Aβ↓,
*ROS↓,
*lipid-P↓, eduction in lipid peroxidation, controlling the GSH levels and then cellular anti-oxidant status improvement,
*GSH↑,
*MDA↓, Silymarin could reduce MDA content and significantly increased the reduced activity level of antioxidant enzyme, including SOD, CAT and GSH in the brain tissue induced by aluminum
*SOD↑,
*Catalase↑,
*AChE↓, Silibinin/ Silymarin, as a strong suppressor of AChE and BChE activity, exerted a positive effect against AD symptoms via increasing the ACh level in the brain
*BChE↓,
*p‑ERK↓, Silibinin could inhibit increased level of phosphorylated ERK, JNK and p38 (p-ERK, p-JNK and p-p38, respectively
*p‑JNK↓,
*p‑p38↓,
*GutMicro↑, demonstrated in APP/PS1 transgenic mice model of AD which was associated with controlling of the gut microbiota by both Silymarin and Silibinin
*COX2↓, Inhibition of the NF-ÎºB pathway/ expression, Inhibition of IL-1Î², TNF-Î±, COX_2 and iNOS level/ expression
*iNOS↓,
*TLR4↓, suppress TLR4 pathways and then subsequently diminished elevated level of TNF-Î± and up-regulated percentage of NF-ÎºB mRNA expression
*neuroP↑, neuro-protective mechanisms on cerebral ischemia (CI)
*Strength↑, Silymarin decreased the loss of grip strength in the experimental rats
*AMPK↑, In SH-SY5Y cells, Silibinin blocked OGD/re-oxygenation- induced neuronal degeneration via AMPK activation as well as suppression in both ROS production and MMP reduction and even reduced neuronal apoptosis and necrosis.
*MMP↑,
*necrosis↓,
*NRF2↑, Silymarin up-regulated Nrf-2/HO-1 signaling (Yuan et al., 2017
*HO-1↑,

3309-

SIL,

Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives

Review,

NA,

*ROS↓, (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut.
*IronCh↑,
*MMP↑, (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance.
*NRF2↑, (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation
*Inflam↓, (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases.
*hepatoP↑,
*HSPs↑, (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins
*Trx↑,
*SIRT2↑, increased expression of protective molecules (GSH, Thioredoxins, heat shock proteins (HSPs), sirtuins, etc.)
*GSH↑,
*ROS↑, Similarly, production of O2− and NO in isolated rat Kupffer cells were inhibited by silibinin in a dose-dependent manner, with IC50 80 μM
*NADPH↓, It also decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue.
*iNOS↓,
*NF-kB↓,
*BioAv↓, active free silibinin concentration in plasma after oral consumption of SM, depending on dose of supplementation, could be in the range 0.2–2.0 μM.
*Dose↝, healthy volunteers, after an oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL
*BioAv↑, For example, silibinin concentration in the gut could reach 800 μM

2410-

SIL,

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

in-vitro,

GBM,

U87MG

in-vitro,

GBM,

U251

in-vivo,

NA,

nude mice

TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo

3955-

Taur,

Mechanism of neuroprotective function of taurine

in-vitro,

NA,

*Ca+2↓, 1. Inhibition of glutamate-induced calcium influx through L-, N- and P/Q-type voltage-gated calcium channels and NMDA receptor calcium channel;
*MMP↑, 2. Attenuation of glutamate-induced membrane depolarization;
*Apoptosis↓, 3. Prevention of glutamate-induced apoptosis via preventing glutamate-mediated down-regulation of Bcl-2;
*Bcl-2↑,
*cal2↓, preventing glutamate-induced membrane depolarization, elevation of [Ca2+]i, activation of calpain, reduction of Bcl-2 and apoptosis.
*LDH↓, LDH release was largely inhibited by taurine

Showing Research Papers: 1 to 50 of 64
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 64

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 1, antiOx↑, 13, Catalase↑, 10, GPx↑, 3, GSH↑, 9, GSR↑, 2, GSTs↑, 1, H2O2↓, 1, HO-1↑, 7, Keap1↓, 1, lipid-P↓, 5, mt-lipid-P↓, 1, MDA↓, 3, Mets↝, 1, MPO↓, 3, NQO1↑, 1, NRF2↑, 6, p‑NRF2↑, 1, OXPHOS↓, 1, OXPHOS↑, 2, ROS?, 1, ROS↓, 35, ROS↑, 1, ROS⇅, 1, mt-ROS↓, 2, SIRT3↑, 3, SOD↑, 11, TOS↓, 1, Trx↑, 1, Trx1↑, 1, UCPs↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 2,

Mitochondria & Bioenergetics ⓘ

ATP↑, 4, ETC↓, 1, MMP↑, 41, MMP⇅, 1, OCR↑, 1, PGC-1α↑, 4,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, ALDOA↑, 1, AMPK↑, 5, BMAL1↑, 1, cAMP↑, 1, p‑CREB↑, 1, ECAR↓, 1, glucose↓, 2, GlucoseCon↑, 1, GlutMet↑, 1, Glycolysis↓, 1, Glycolysis↑, 1, GPI↑, 1, HK2↑, 1, LDH↓, 1, LDHA↑, 1, LDL↓, 1, NADH:NAD↑, 1, NADPH↓, 2, PFKL↑, 1, PKM1↑, 1, PPARα↑, 1, PPARγ↑, 3, SIRT1↑, 4, SIRT2↑, 1,

Cell Death ⓘ

Akt↓, 1, p‑Akt↑, 1, APAF1↓, 1, Apoptosis↓, 11, BAX↓, 2, Bax:Bcl2↓, 1, Bcl-2↑, 2, Casp3↓, 7, cl‑Casp3↓, 1, Casp9↓, 2, cl‑Casp9↓, 1, Cyt‑c↓, 5, Cyt‑c∅, 2, iNOS↓, 5, p‑JNK↓, 1, MAPK↓, 3, necrosis↓, 1, p‑p38↓, 1, TRPV1↑, 1,

Transcription & Epigenetics ⓘ

Ach↑, 2, other↑, 3, other↝, 2,

Protein Folding & ER Stress ⓘ

ATF6↓, 2, CHOP↓, 2, ER Stress↓, 2, GRP78/BiP↓, 3, HSP70/HSPA5↑, 1, HSP70/HSPA5↝, 1, HSPs↑, 2, IRE1↓, 1, PERK↓, 1,

DNA Damage & Repair ⓘ

DNAdam↓, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1, ERK↑, 2, p‑ERK↓, 2, FOXO↑, 1, GSK‐3β↓, 2, GSK‐3β↑, 1, IGF-1↑, 1, PI3K↓, 1, Src↓, 1, STAT3↓, 1,

Migration ⓘ

AntiAg↑, 1, AP-1↓, 1, Ca+2?, 1, Ca+2↓, 6, i-Ca+2↓, 1, cal2↓, 1, CXCL12↑, 1, MMP2↓, 1, MMP3↓, 1, MMP9↓, 4, MMP9↑, 1, ZO-1↑, 1, β-catenin/ZEB1↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 2, CLDN5↑, 1, Hif1a↑, 1, NO↓, 4, PDI↓, 1,

Barriers & Transport ⓘ

BBB?, 1, BBB↓, 1, BBB↑, 6, BBB↝, 1,

Immune & Inflammatory Signaling ⓘ

COX1↓, 1, COX2↓, 6, CRP↓, 1, CXCR4↓, 1, HMGB1↓, 1, IL10↑, 1, IL17↓, 1, IL18↓, 2, IL1β↓, 8, IL4↓, 1, IL6↓, 3, Inflam↓, 12, NF-kB↓, 10, p65↓, 1, PAR-2↓, 1, PGE2↓, 4, TLR4↓, 2, TNF-α↓, 7,

Synaptic & Neurotransmission ⓘ

AChE↓, 6, BChE↓, 2, BDNF↑, 3, tau↓, 1, p‑tau↓, 2,

Protein Aggregation ⓘ

Aβ↓, 11, NLRP3↓, 1, β-Amyloid↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 4, BioAv↑, 2, BioAv↝, 2, Dose⇅, 1, Dose↝, 4, Dose∅, 1, eff↑, 8, eff↝, 1, Half-Life↓, 1, Half-Life↝, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, AST↓, 2, BMD↑, 1, BP↓, 1, creat↓, 1, CRP↓, 1, GutMicro↑, 2, IL6↓, 3, LDH↓, 1,

Functional Outcomes ⓘ

AntiAge↑, 2, AntiTum↑, 1, cardioP↑, 2, cognitive↑, 6, hepatoP↑, 3, memory↑, 9, motorD↑, 3, neuroP↑, 21, RenoP↑, 1, Strength↑, 1, toxicity∅, 1,

Infection & Microbiome ⓘ

Sepsis↓, 1,
Total Targets: 184

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential

5 Honokiol
5 Thymoquinone
4 Magnetic Fields
4 Quercetin
4 Taurine
3 Baicalein
3 Boron
3 Capsaicin
3 Silymarin (Milk Thistle) silibinin
2 Silver-NanoParticles
2 Alpha-Lipoic-Acid
2 EGCG (Epigallocatechin Gallate)
2 Ferulic acid
2 Luteolin
2 Resveratrol
2 Rosmarinic acid
2 Vitamin K2
1 Apigenin (mainly Parsley)
1 Astaxanthin
1 Baicalin
1 Celastrol
1 Chrysin
1 Curcumin
1 Electrical Pulses
1 Ginkgo biloba
1 doxorubicin
1 Lycopene
1 Moringa oleifera
1 Propolis -bee glue
1 Ursolic acid
1 Urolithin
1 Vitamin B5,Pantothenic Acid
1 Vitamin C (Ascorbic Acid)

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:197  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

MMP Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

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 ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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