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, NA
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
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
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, NA
*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
*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, NA - Review, Stroke, NA - Review, IBD, NA - Review, Arthritis, NA - Review, AD, NA - Review, Park, NA
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/PTGS2↓, 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,

6496- BCP,    β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models
- vitro+vivo, CRC, HCT116 - in-vitro, Nor, HUVECs
angioG↓, BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of
VEGF↓,
TumVol↓, BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively.
Apoptosis↑, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions.
HSP60/HSPD1↓,
HTRA↓,
survivin↓,
XIAP↓,
P21↑,
*toxicity↓, Notably, it is responsible for the spiciness of black pepper, and has been widely used as a safe food flavoring additive with official approval from the Food and Drug Administration
*neuroP↑, BCP was reported to exert a neuroprotective effect in human neuroblastoma SH-SY5Y cells
*ROS↓, intraperitoneally injected BCP at the dose of 50 mg/kg for one month has successfully attenuated oxidative stress, inhibited inflammatory mediator cyclooxygenase-2 and reduced neuroinflammation
*COX2/PTGS2↓,
*Inflam↓,
*cardioP↑, BCP has been recently shown to exert a remarkable cardioprotective effect against doxorubicin-induced acute cardiotoxicity in albino Wistar rats
AntiCan↑, in vitro studies have suggested that BCP exerts significant anti-cancer effects against different types of cancer cell lines.
ChemoSen↑, BCP potentiated the anti-cancer activity of paclitaxel on human colorectal adenocarcinoma (DLD-1), human breast cancer (MCF-7), and murine fibroblast (L-929) cells.
ROS↑, reported to induce apoptosis of human epidermoid skin cancer cells, mediated by production of reactive oxygen species with loss of mitochondrial membrane potential, as well as alteration of specific apoptotic markers like an increase in Bax/Bcl-2 rat
MMP↑,
Bax:Bcl2↑,
TumCG↓, BCP Inhibited Tumor Growth in an HCT-116 Cells Transplanted Mouse Xenograft Model

3505- Bor,    Mineral requirements for mitochondrial function: A connection to redox balance and cellular differentiation
- Review, NA, 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, NA
*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.

6542- BSB,    Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol
- Review, Var, NA - Review, Park, NA - Review, AD, NA
AntiCan↑, Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial.
*neuroP↑,
*cardioP↑,
*AntiBio↑,
*BioAv↑, Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant wit
*toxicity↓,
*BioAv↑, integrated in many cosmetic formulations due to its skin soothing effects, well documented dermal absorption
*motorD↑, improvement in locomotor activity, a reduction in the expression of thiol and a reinstate of the activity of mitochondrial complex-I.
*SOD↑, α-Bisabolol also increased the mRNA level of antioxidants proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product.
*Catalase↑,
*Keap1↑,
*MDA↓, α-Bisabolol attenuated oxidative insult by reducing malondialdehyde (MDA), restoring depleted glutathione (GSH) and improving SOD and CAT activity.
*GSH↑,
*IL1β↓, attenuated neuroinflammation by reducing glial cells activation and subsequent release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and mediators (iNOS and COX-2).
*IL6↓,
*TNF-α↓,
*iNOS↓,
*COX2/PTGS2↓,
*lipid-P↓, α-Bisabolol restored mitochondrial function by preventing mitochondrial lipid peroxidation, cytochrome-C release and most importantly preserving Complex-I activity
*Cyt‑c↓,
*ROS↓, The study concluded that α-Bisabolol safeguarded against the induced upsurge of ROS and nitrite.
*MMP↑, α-Bisabolol treatment also restored mitochondrial membrane potential (MMP) validating its antioxidant effect.
*antiOx↑,
*AChE↓, showed a significant reduction in AChE activity and an ability to avert Ach depletion.
*Apoptosis↓, α-Bisabolol protected cells from Aβ triggered apoptosis by reducing Bax and Caspase-3 and increasing Bcl-2 activity.
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BACE/β-secretase↓, α-Bisabolol inhibitory activity on BACE1 and found a decrease in BACE1 activity following α-Bisabolol treatment
*BChE↓, AChE, BuChE, β-secretase actions were decreased significantly in cells pretreated with α-Bisabolol
*eff↑, The compound clearly illustrated a potent anti-AchE activity of 95.869% similar to the activity of donepezil, a standard drug. I
*Aβ↓, The compound also disaggregated Aβ25–35 peptide and protected against its induced toxicity by increasing neuro2a cells viability [
*ATP↑, figure 2
RadioS↑, α-Bisabolol and Anticancer Effects, figure 3
Cyt‑c↑,
Casp3↑,
Casp8↑,
Casp9↑,
Apoptosis↑,
PARP↑,
BAX↑,
BID↑,
NF-kB↑,
Fas↑,
EGFR↑,
TIMP2↑,
XIAP↓,
COX2/PTGS2↓,
Bak↓,
Bcl-2↓,
P53↑, The expression of p53 (a transcription factors whose products might lead to apoptosis), NF-κB and Fas was increased following α-Bisabolol treatment, indicating their function in mediating α-Bisabolol-induced apoptosis in the cancer cell line.
HER2/EBBR2↓,
FGF↓,
CEA↓,
Akt↓,
TumCCA↑, α-Bisabolol suppresses the cellular proliferation at G2/M cell cycle phase.
*Imm↑, reported that α-Bisabolol boosted the immunity response by T-cell subsets (CD4 and CD8) supplementation in treated mice.
*CD4+↑,
*CD8+↑,
*BBB↑, ↑ BBB penetration
*Pain↓, α-Bisabolol based mouthwash to that of chlorhexidine in reducing pain during brushing
*cardioP↑, α-Bisabolol and Cardioprotection, figure 5
*TBARS↓, rats co-treated with α-Bisabolol showed reduced LOOH and TBARS and increased SOD, CAT and GSH.
*SOD↑,
*Catalase↑,
*GSH↑,
*AntiBio↑, α-Bisabolol demonstrated an antibacterial effect against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa as well as a synergism against S. aureus, when combined with the antibiotic norfloxacin and against E. coli when combined with
*AntiFungal↑, ↓ fungal growth
*GastroP↑, α-Bisabolol and Gastroprotection. oral administration of α-Bisabolol was realized to attenuate gastric damage and to provide cytoprotection in stomach.
*RenoP↑, The nephroprotective effects of α-Bisabolol and the underlying mechanisms are summarized in Table 10.
*creat↓, ↓ creatinine, urea, uric acid
*uricA↓,
*Inflam↓, Anti-Inflammatory Effects of α-Bisabolol
*iNOS↓, ↓ iNOS, COX-2, TNF-α, p65 PGE2, nitrite, IL-6, ↓ MMP13
*COX2/PTGS2↓,
*TNF-α↓,
*IL6↑,
*MMP13↓,

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, NA
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, NA - Review, IBD, NA - Review, AD, NA - Review, Park, NA
*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/PTGS2↓,
*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, NA
*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/PTGS2↓,
*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/PTGS2↑, 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↓,

6631- Cic,    Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity.
- in-vitro, Nor, NA
*MMP↑, chicoric acid mitigates apoptotic features caused by oxLDL, such as the subsequent break down of mitochondrial transmembrane potential and the activation of Bax, which promote DNA strand breaks and activate caspase-3.
*BAX↓,
*DNAdam↓,
*Casp3↓,
*NF-kB↓, attenuated the oxLDL activation of NF-κB,
*antiOx↑, anti-oxidant action and anti-inflammation capacity
*Inflam↓,

3831- CUR,    Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease
- Review, AD, NA
*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↑,

6249- Cyc,    Cyclopamine tartrate, an inhibitor of Hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H1299
HH↓, Cyclopamine was the first compound found to inhibit Hh signaling and has been invaluable for understanding the function of Hh signaling in development and cancer.
OCR↓, Our results showed that CycT, like glutamine depletion, caused a substantial decrease in oxygen consumption in a number of NSCLC cell lines,
TumCP↓, suppressed NSCLC cell proliferation, and induced apoptosis.
Apoptosis↑,
ROS↑, we found that CycT increased ROS generation, mitochondrial membrane hyperpolarization, and mitochondrial fragmentation, thereby disrupting mitochondrial function in NSCLC cells.
MMP↑, We found that CycT increases mitochondrial membrane potential substantially in NSCLC cells
mtDam↑,

7208- EGb 761,    EGb 761 reduces Ca2+ influx and apoptosis after pentylenetetrazole treatment in a neuroblastoma cell line
- in-vitro, Nor, SH-SY5Y
*Ca+2↑, EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis,
*Apoptosis↓, EGb 761 reduces apoptosis and intracellular reactive oxygene species levels in the pentylenetetrazole-induced in vitro neurotoxicity model in the SH-SY5Y cells
*ROS↓, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of EGb 761 in the pentylenetetrazole-induced epileptogenesis process.
*MMP↑, EGb 761 reduces mitochondrial depolarization, caspase 3, and caspase 9 in the pentylenetetrazole induced in vitro neurotoxicity model in SH-SY5Y cells
*Casp3↓,
*Casp9↓,

7235- EGb 761,    Stabilization of Mitochondrial Membrane Potential and Improvement of Neuronal Energy Metabolism by Ginkgo Biloba Extract EGb 761
- in-vitro, AD, NA
*MMP↑, EGb 761 given shortly after initiating mitochondrial damage by sodium nitroprusside (nitric oxide donor) improved the mitochondrial membrane potential of PC12 cells significantly and dose dependently.
*ATP↑, EGb 761 also reversed the decrease in ATP production. In addition, similar protection against oxidative damage was found in dissociated brain cells and isolated brain mitochondria after in vitro or in vivo treatment with EGb 761.

7219- EGb 761,    Ginkgo biloba Prevents Oxidative Stress-Induced Apoptosis Blocking p53 Activation in Neuroblastoma Cells
- in-vitro, Nor, SK-N-BE
*MMP↑, a reduction in mitochondrial membrane potential, an increased BAX/Bcl-2 ratio and consequently increased Poly (ADP-ribose) polymerase (PARP) cleavage. All these effects were blocked by EGb 761 treatment.
*Bax:Bcl2↓,
*cl‑PARP↓,
*i-antiOx↑, EGb 761, acting as intracellular antioxidant, protects neuroblastoma cells against activation of p53 mediated pathway and intrinsic mitochondrial apoptosis.
*mt-Apoptosis↓,
*neuroP↑, Our results suggest that EGb 761, protecting against oxidative-stress induced apoptotic cell death, could potentially be used as nutraceutical for the prevention and treatment of neurodegenerative diseases.

3721- EGb 761,    Ginkgo biloba Extract in Alzheimer’s Disease: From Action Mechanisms to Medical Practice
- Review, AD, NA
*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↑,

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
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/DDIT3↑, 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, NA
*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↓,

6828- EMD,    Neuroprotective effect of emodin against Alzheimer's disease via Nrf2 signaling in U251 cells and APP/PS1 mice
- in-vitro, AD, U251
*MMP↑, emodin ameliorated the dissipation of the mitochondrial membrane potential, inhibited the over-accumulation of reactive oxygen species, enhanced the expression levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), haemeoxygenase-1, superoxide
*ROS↓,
*NRF2↑,
*HO-1↑,
*SOD↑, superoxide dismutase 1, Bcl-2 and catalase in addition to decreasing the expression levels of Bax.
*Bcl-2↑,
*Catalase↑,
*BAX↓,
*memory↑, In APP/PS1 mice, an 8-week course of emodin administration improved spatial memory and learning ability and decreased anxiety.
*ANXi↓,
*Aβ↓, decreased the deposition of Aβ, phosphorylated-τ and 4-hydroxy-2-nonenal in APP/PS1 mice
*antiOx↑, In addition, emodin exhibits antioxidative effects: In viral myocarditis, emodin alleviates oxidative stress by increasing myocardial SOD expression levels whilst decreasing malondialdehyde expression levels
*MDA↓,

5523- EP,    Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication
- vitro+vivo, Nor, HUVECs
*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, NA
*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, NA
*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↑,

6981- Form,    Formononetin: a review of its source, pharmacology, drug combination, toxicity, derivatives, and drug delivery systems
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
BioAv↝, FMN has only one phenolic hydroxyl group, so it is poorly soluble in water and easily soluble in organic solvents such as methanol, ethyl acetate, and ether.
*memory↑, It had been found that FMN, isolated from Sophora secundiflora, could improve memory problems by restoring the level of oxidative stress in brain tissues and modulating acetylcholinesterase activity. I
*ROS↓, findings suggest that FMN can inhibit oxidative stress in the liver and restore mitochondrial function
*AChE↓,
*NF-kB↓, FMN, the expression levels of the above three decreased and NF-κB activation was inhibited, which may be related to the release of FMN blocking kelch-like ECH-associated protein-1 (Keap1) and activating the nuclear factor erythroid 2-related factor 2
*Keap1↝,
*NRF2↑,
*Inflam↓, FMN exerted anti-neuroinflammatory effects by targeting peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and bidirectionally regulating NF-κB signaling pathway and Nrf2/Heme oxygenase-1 (HO-1) signaling pathway,
*PGC-1α↝,
*HO-1↓,
*p‑tau↓, thereby inhibiting tau protein hyperphosphorylation.
*cognitive↑, Significantly FMN improve cognitive dysfunction in mice caused by high-fat feeding
*BDNF↑, increased BDNF and 5-hydroxytryptamine (5-HT) levels, and mitigated the progression of depression in mice.
*5HT↑,
*Stroke↓, It could significantly reduce the level of inflammatory factors, increase the number of dendritic spines in neurons, and increase the expression of βIII-tubulin, growth-associated protein 43 (GAP-43), nerve growth factor (NGF) and BDNF.
*PARP1↓, FMN significantly reduced PARP1, PARG, apoptosis-inducing factor (AIF), cysteinyl aspartate-specific protease 3 (caspase-3) and p53 protein in rats with cerebral ischemia-reperfusion injury
*AIF↓,
*Casp3↓,
NP/CIPN↓, FMN had a favorable ameliorative effect on oxaliplatin-induced peripheral neuropathy and did not affect the chemotherapeutic function of oxaliplatin.
*neuroP↑, The neuroprotective mechanism of FMN is shown in Figure 2.
*NGF↑,
*TNF-α↓,
*IL1β↓,
*IL18↓,
*IL6↓,
*VCAM-1↓,
*pol-M2 MC↑,
*hepatoP↑, could reduce hepatotoxicity and improve liver function through inflammatory molecular pathways.
*AST↓, reduce serum AST, ALT, TNF-α and IL-1β levels. I
*ALAT↓,
*LC3II↑, the levels of LC3II, Beclin1, p62, cyclooxygenase-2 (COX2), COX4, MMP and adenosine triphosphate (ATP) were increased
*Beclin-1↑,
*p62↑,
*COX2/PTGS2↑,
*MMP↑,
*ATP↑,
*GSH↑, activity of antioxidant proteins glutathione (GSH), catalase (CAT), GSH-PX in the FMN treatment group recovered, and the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) decreased.
*Catalase↑,
*GPx↑,
*MDA↓,
*antiPs↑, it was found that the interferon (IFN) signaling pathway was inhibited, which could effectively reduce the expression of related inflammatory chemokines, and significantly improve the erythema, scales and thickness of skin lesions in the psoriasis m
*AntiDiabetic↑, FMN effectively mitigated alloxan-induced pancreatic β-cell and DNA damage, lowered blood glucose levels, and increased insulin content.
*glucose↓,
*Insulin↑,
*GutMicro↑, FMN could act as a prebiotic to regulate intestinal microbial flora, thereby improving host metabolism and preventing obesity
*Obesity↓,
COX2/PTGS2↓, FMN effectively inhibited the proliferation of KYSE170 and KYSE150 cells by significantly reducing the mRNA and protein expression levels of COX-2 and cyclin D1, while inducing G1 phase arrest.
cycD1/CCND1↓,
TumCCA↑,
EGFR↓, FMN binds to both WT and mutant EGFR, reducing EGFR kinase activity and inhibiting downstream signaling.
GSK‐3β↑, This, in turn, activated GSK-3β and decreased the expression of myeloid leukemia sequence 1 (Mcl-1), without causing significant toxicity to the vital organs of mice.
Mcl-1↓,
*toxicity↓,
TumCP↓, FMN inhibited the proliferation and growth of cervical cancer cells by inhibiting the expression of HIF-1-α and VEGF.
Hif1a↓,
VEGF↓,
ERK↓, can achieve antiproliferative and invasive effects through effective inhibition of the oncogenic ERK1/2 pathway and the Lamin A/C signaling pathway,
LAMs↓,
Cyt‑c↑, FMN, as a candidate anticancer drug, could release cytochrome C (cyto C) directly through the mitochondrial pathway and activate the cascade reaction of caspase-9, caspase-3 and PARP, which ultimately lead to FaDu cell death
Casp9↑,
Casp3↑,
PARP↑,
TumCD↑,
mitA↑, FMN inhibited mitosis by inactivating the BACH1/p53 signaling pathway, promoted the release of cyto C
BACH1↓,
P53↓,
ROS↑, FMN delivered ROS to mitochondria to release cyto C and activated caspase-3 and caspase-9 cascade reactions to induce apoptosis in MCF7 cells
PD-1↓, FMN has the potential to serve as a PD-1/PD-L1 inhibitor for clinical use
NF-kB↓, FMN mainly interfered with PD-L1 activation by inhibiting the STING-NF-κB signaling pathway
*Bacteria↓, possess other pharmacological activities, such as antibacterial, antiviral, and antiallergic
*AntiViral↑,
*mt-ROS?, FMN effectively reduced the accumulation of ROS and mitochondrial damage in hair cells by activating the PI3K/AKT-Nrf2 signaling pathway, restored the balance of GSH/GSSG.
*PI3K↓,
*chemoP↑, FMN was a potential therapeutic agent for cisplatin-induced ototoxicity.
ChemoSen↑, Therefore, combination therapy had better control effects on multiple targets and a lower risk of drug resistance, which had great application prospects for treating cancer.
eff↑, combination of FMN (30 μM) and sulforaphane (20 μM) exhibited a significant synergistic effect
*toxicity↓, Therefore, it was proved that FMN was safe and non-toxic and could be used for pharmacological and therapeutic purposes.
*BioAv↑, water solubility problem of FMN, succinylated FMN using Bacillus amyloliquefaciens FJ18 to form the compound FMN-7-O-β-D (6″-O-succinyl)-D-glucoside (FMP), which compared to FMN, the water solubility was increased more than 106-fold.
*BioAv↑, To solve those problems, structural modification and nano-delivery systems can be used as a promising solution
*eff↑, FMN can be combined with other treatments, such as immunotherapy, to enhance the therapeutic effect and improve the prognosis of patients;

7311- Gos,    Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials
- Review, CLL, NA
Dose↝, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation.
toxicity↓,
PFS↓, Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival.
OS↑,
eff↑, most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival o
BioAv↑, The gossypol (−)-enantiomer—also called AT-101—is degraded more slowly and is therefore the more biologically active form
Bcl-2↓, AT-101, a natural Bcl-2 homology domain 3 (BH3) mimetic, is a small molecule inhibitor that downregulates anti-apoptotic Bcl-2 and Bcl-2-related proteins in human cancer cells
ROS↑, In addition, gossypol-induced intrinsic apoptosis might occur also as reactive oxygen species (ROS)-independent
MOMP↑, In gossypol-treated cancer cells, alterations on the mitochondrial outer membrane permeabilization (MOMP) cause the release of large amounts of apoptotic markers, such as cytochrome c and apoptosis-inducing factor (AIF),
Dose↑, Thereby, the maximum tolerated gossypol dose was determined to be 0.8 mg/kg per day (50–60 mg/day),
Casp3↑, Gossypol-induced apoptosis appears to proceed via the caspase-dependent pathway by activation of caspase-3 and caspase-9
Casp9↑,
MMP↑, as well as mitochondrial membrane depolarization
VEGF↓, suppression of vascular endothelial growth factor (VEGF) stimulating intracellular pro-angiogenic kinases phosphorylation could be inhibited by AT-101
APE1/APEX1↓, addition of gossypol leads to inhibition of APE1 and enhances the activity of cisplatin in non-small cell lung cancer
ChemoSen↑,
RadioS↑, Moreover, AT-101 was demonstrated to radiosensitize prostate cancer in vitro and in vivo without augmenting toxicity
toxicity↑, hematologic toxicities are common treatment related toxicities
AST↑, he majority of related AEs were GI and nervous system disorders, increased AST/ALT, of grade 1/2 toxicities
ALAT↑,

7482- H2,    Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA - Review, Sepsis, NA - Review, AD, NA
Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

7483- H2,  Cisplatin,    Molecular hydrogen attenuates cisplatin-induced nephrotoxicity by modulating β-hydroxybutyrate metabolism
- in-vivo, Nor, HK-2
RenoP↑, H2 inhalation significantly attenuated cisplatin-induced kidney injury by reducing inflammation and apoptosis in renal tissue.
BHB↑, H2 upregulated the ketone body metabolic pathway, particularly enhancing β-hydroxybutyrate (β-HOB) synthesis via increased expression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2).
HMGCS2↑,
chemoP↑, Molecular hydrogen confers protection against cisplatin-induced nephrotoxicity by modulating β-HOB metabolism through upregulation of HMGCS2, thereby suppressing renal inflammation and apoptosis.
*IL2↓, IL-1β, IL-6, MCP-1, and TNF-α in kidney tissue. Levels of these proinflammatory mediators were significantly elevated following cisplatin treatment. H2 inhalation significantly suppressed these cytokines,
*IL6↓,
*MCP1/CCL2↓,
*TNF-α↓,
*KeyT↝, H2 upregulated HMGCS2 to enhance ketone body metabolism
*Inflam↓, H2 has been demonstrated protective effects in various inflammatory and oxidative stress-related conditions
*ROS↓,
*MMP↑, Several studies have shown that H2 can preserve mitochondrial membrane potential, boost ATP generation, and improve mitochondrial dynamics and biogenesis by activating pathways such as mitofusin-2 (Mfn2) and PGC-1α
*ATP↑,
*MFN2↑,
*PGC-1α↑,
*BUN↓, Our work confirmed that H2 inhalation significantly ameliorated cisplatin-induced histological damage, elevated BUN and creatinine levels, renal inflammation, and tubular apoptosis.
*creat↓,

2869- HNK,    Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's
- Review, AD, NA - Review, Park, NA
*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/DDIT3↓,
*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, NA
*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.

2071- HNK,    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient
- Review, Nor, HaCaT
*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 - NA, Park, NA
*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↓,

7636- Ins,    Myo-Inositol: Pharmacokinetics, Biological Functions, and Therapeutic Potential in Liver Protection: Insights from Preclinical Models
*glucose↝, Myo-inositol, the most common stereoisomer of inositol, plays an important role in many physiological processes, such as cell signaling, regulation of glucose and lipid metabolism, and protection of cells against oxidative stress.
*lipid-P↓,
*ROS↓,
*BioAv↑, characterized by high oral bioavailability and is primarily eliminated via the kidneys.
*hepatoP↑, Preclinical studies have shown that myo-inositol has hepatoprotective potential, reducing oxidative stress, inflammation, and lipid accumulation in hepatocytes,
*Inflam↓,
*MMP↑, Recent findings suggest that it contributes to the stabilization of mitochondrial membranes and enhances ATP production efficiency,
*ATP↑,
*GutMicro↑, Evidence indicates that myo-inositol may influence intestinal microbiota composition, enhancing populations of beneficial bacterial strains while reducing endotoxemia linked to non-alcoholic fatty liver disease
*Dose↝, a significant portion of the body’s requirement is also supplied by the diet-rich sources, including fruits, whole grains, legumes, and nuts.
*Half-Life↝, Studies on rats has revealed that the highest plasma concentrations were observed within 1–2 h after oral intake, while the half-life ranged from 4 to 8 h.
*BioAv↑, In the case of intravenous administration, higher bioavailability and faster tissue distribution were achieved. intravenous administration of myo-inositol is rare
*eff↑, myo-inositol supplementation may potentially synergize with antioxidants (e.g., vitamin E, curcumin), enhancing their protective effects on the liver and other organs exposed to oxidative stress
*hepatoP↑, Myo-inositol may exert hepatoprotective effects through several biological mechanisms. A key role is played by its involvement in lipid metabolism regulation, modulation of oxidative stress, and influence on insulin signaling.
*SOD↑, Moreover, myo-inositol and its derivatives (including D-chiro-inositol) affect the activation of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, thereby limiting oxidative damage to hepatocytes
*Catalase↑,
*Casp3↓, inhibit the expression of apoptosis markers such as caspase-3,
*ALAT↓, decreased activity of transaminases (ALT, AST).
*AST↓,
*AMPK↑, regulation of lipid metabolism through the activation of AMP-activated protein kinase (AMPK) and downregulation of sterol regulatory element-binding proteins (SREBPs).
*SREBP1/SREBF1↑,
*NA↑,

7876- isoO,    Isoorientin exerts a protective effect against 6-OHDA-induced neurotoxicity by activating the AMPK/AKT/Nrf2 signalling pathway
- in-vitro, Nor, NA
*neuroP↑, IOT significantly inhibited neurotoxicity reduced apoptotic cell numbers, reactive oxygen species (ROS) overproduction and mitochondrial membrane potential, and modulated the expression of apoptosis-related proteins, incluced by 6-OHDA
*ROS↓,
*MMP↑,
*GCLC↑, IOT also enhanced the expression of the GCLC, GCLM, HO-1, NQO1 and Trx-1 proteins, which mostly depends on the nuclear translation of Nrf2 and reduced expression of the Keap1 protein.
*GCLM↑,
*HO-1↑,
*NQO1↑,
*Trx1↑,
*NRF2↑,
*Keap1↓,
*p‑AMPK↑, IOT significantly increased the phosphorylation of AMPK, ERK, GSK3β, JNK, PI3K and AKT.
*p‑ERK↑,
*p‑GSK‐3β↑,
*p‑JNK↑,
*p‑PI3K↑,
*p‑Akt↑,
*AMPK↑, IOT might play a protective role against 6-OHDA-induced neurotoxicity by inducing the expression of various antioxidant enzymes via the activation of the AMPK/AKT-Nrf2 signalling pathway.
*Akt↑,

7872- isoO,    Isoorientin ameliorates H2O2-induced apoptosis and oxidative stress in chondrocytes by regulating MAPK and PI3K/Akt pathways
- in-vivo, Arthritis, NA
*antiOx↑, Isoorientin (ISO) is a natural plant extract that has antioxidant activity and could be used to treat OA
*MMP↑, combination of ISO and H2O2 significantly reduced apoptosis and restored mitochondrial membrane potential (MMP), which may be achieved by inhibiting apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways.
*Apoptosis↓, ISO inhibits H2O2-induced chondrocytes apoptosis
*MAPK↓,
*SOD↑, ISO increased superoxide dismutase (SOD), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) and reduced malondialdehyde (MDA) levels.
*HO-1↑, ISO increased Nrf2 levels as well as HO-1 and NQO-1 protein expression, implying Nrf2/keap1 activation.
*NQO1↑,
*MDA↓,
*ROS↓, ISO inhibited H2O2-induced intracellular reactive oxygen species (ROS) in chondrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathways.
*NRF2↑, ISO protects against oxidative damage by increasing the activity of antioxidant enzymes and activating the Nrf2 antioxidant pathway
*PI3K↑,
*Akt↑,

7800- ISQ,    Isoquercitrin Attenuates Oxidative Liver Damage Through AMPK-YAP Signaling: An Integrative In Silico, In Vitro, and In Vivo Study
- vitro+vivo, Nor, HepG2
*antiOx↑, Isoquercitrin, a flavonoid glycoside found in various plants, has demonstrated antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
*AntiCan↑,
*ROS↓, HepG2 cells exposed to arachidonic acid (AA) and iron exhibited oxidative stress-induced apoptosis, which was significantly attenuated by isoquercitrin treatment
*MMP↑, Isoquercitrin decreased reactive oxygen species (ROS) generation and preserved mitochondrial function in a dose-dependent manner.
*STK11/LKB1↑, isoquercitrin activates the LKB1/AMPK pathway, increasing phosphorylation of AMPK and its downstream target ACC, thereby modulating energy metabolism and reducing oxidative stress.
*AMPK↑,
*p‑AMPK↑,
*ACC↑,
*ALAT↓, isoquercitrin protected mice against carbon tetrachloride-induced liver injury, reducing serum ALT and AST levels and improving histopathological features.
*AST↓,
*hepatoP↑, isoquercitrin exerts hepatoprotective effects by activating the LKB1/AMPK pathway and modulating metabolic enzymes, highlighting its potential as a therapeutic agent against oxidative liver damage.

2904- LT,    Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons
- in-vitro, Park, SK-N-SH - in-vitro, AD, NA
*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, NA - Review, AD, NA - Review, Park, NA
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, NA
*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.

6418- MEL,  RES,    Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation
- in-vivo, AD, NA
*neuroP↑, We show that melatonin prevents Cd-induced nephrotoxicity by inhibiting dynamin-related protein 1 (Drp1)- and mitochondrial fission protein 1 (Fis1)-mediated mitochondrial fission.
*DRP1/DNM1L↓,
*FIS1↓,
*ROS↓, Melatonin treatment attenuated cytotoxicity, suppressed oxidative stress, restored mitochondrial membrane potential, and increased mitochondrial mass in response to Cd exposure.
*MMP↑,
*SIRT1↑, melatonin treatment increased Cd-inhibited sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression
*PGC-1α↑,
*eff↑, Like melatonin, SIRT1 overexpression via resveratrol attenuated Drp1- and Fis1-mediated mitochondrial fission and other Cd-induced mitochondrial oxidative injuries effectively.

2242- MF,    Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair
- in-vitro, Nor, NA
*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.


Showing Research Papers: 1 to 50 of 84
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 84

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

APE1/APEX1↓, 1,   BHB↑, 1,   CD47↓, 1,   HMGCS2↑, 1,   HSP60/HSPD1↓, 1,   HTRA↓, 1,   miR-124-3p↓, 1,   PFS↓, 1,   PFS↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 2,   GPx↓, 1,   HO-1↓, 1,   lipid-P↑, 1,   NRF2↓, 3,   OXPHOS↓, 1,   ROS↓, 1,   ROS↑, 15,   SOD↓, 2,   Trx1↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP∅, 1,   CDC2↓, 1,   ETC↓, 1,   MMP↓, 1,   MMP↑, 10,   mtDam↑, 2,   OCR↓, 1,   PGC-1α↑, 1,   XIAP↓, 4,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   ALAT↑, 1,   HK2↓, 1,   lactateProd↓, 1,   LDH↓, 2,   LDL↓, 1,   NADPH↑, 1,   PDK1↓, 1,   PPARα↓, 1,   SCD1↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 6,   p‑Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 11,   BAD↑, 1,   Bak↓, 1,   Bak↑, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 1,   BID↑, 1,   Casp3↑, 7,   Casp8↓, 1,   Casp8↑, 2,   Casp9↑, 4,   proCasp9↓, 1,   Cyt‑c↑, 4,   DR5↑, 1,   Fas↑, 3,   FasL↑, 1,   hTERT/TERT↓, 2,   IAP2/BIRC3↓, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↑, 1,   Mcl-1↓, 2,   MDM2↓, 1,   MOMP↑, 1,   Myc↓, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

EZH2↓, 1,   other↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 2,   HSP90↓, 1,   UPR↑, 2,   XBP-1↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↑, 2,   BNIP3↑, 1,   BNIP3↝, 1,   LC3B↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 2,   P53↓, 1,   P53↑, 2,   PARP↑, 4,   TP53↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 2,   CDK4↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   mitA↑, 1,   P21↑, 1,   TumCCA↑, 6,  

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

CSCs↓, 1,   EMT↓, 2,   ERK↓, 2,   p‑ERK↓, 1,   FGF↓, 1,   FOXO3↑, 1,   GSK‐3β↑, 1,   HDAC↓, 1,   HH↓, 1,   IGF-1R↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↑, 1,   NOTCH3↓, 1,   PI3K↓, 3,   p‑PI3K↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TOP1↓, 1,   TumCG↓, 2,   Wnt↑, 1,  

Migration(tgid=13) ⓘ

BACH1↓, 1,   Ca+2↑, 1,   CEA↓, 1,   CLDN1↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   Fibronectin↓, 1,   LAMs↓, 1,   MALAT1↓, 1,   MMP-10↓, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   Slug↓, 1,   Snail↓, 2,   TET1↑, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 5,   Twist↓, 2,   Vim↓, 2,   Zeb1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 3,   ATF4↑, 1,   EGFR↓, 2,   EGFR↑, 1,   p‑EGFR↓, 1,   Hif1a↓, 4,   VEGF↓, 7,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2,   COX2/PTGS2↑, 1,   IL1↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 1,   NF-kB↓, 2,   NF-kB↑, 1,   NK cell↑, 1,   PD-1↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 6,   Dose↑, 1,   Dose↝, 4,   eff↑, 7,   RadioS↑, 4,   selectivity↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   ALAT↑, 1,   ALP↓, 1,   AST↑, 1,   CEA↓, 1,   EGFR↓, 2,   EGFR↑, 1,   p‑EGFR↓, 1,   EZH2↓, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 2,   IL6↓, 2,   LDH↓, 2,   Myc↓, 1,   TP53↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 4,   AntiTum↑, 1,   cardioP↑, 4,   chemoP↑, 3,   chemoPv↑, 2,   cognitive↑, 1,   neuroP↑, 1,   NP/CIPN↓, 2,   OS↑, 2,   QoL↑, 1,   radioP↑, 1,   RenoP↑, 2,   toxicity↓, 1,   toxicity↑, 1,   TumVol↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,  
Total Targets: 209

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 2,   compII↑, 1,   NA↑, 1,   Stroke↓, 2,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 14,   i-antiOx↑, 1,   Catalase↑, 13,   GCLC↑, 1,   GCLM↑, 1,   GPx↑, 4,   GSH↑, 8,   GSR↑, 2,   GSTs↑, 1,   HO-1↓, 1,   HO-1↑, 8,   Keap1↓, 1,   Keap1↑, 1,   Keap1↝, 1,   lipid-P↓, 4,   MDA↓, 5,   MFN2↑, 1,   MPO↓, 3,   NQO1↑, 2,   NRF2↑, 7,   p‑NRF2↑, 1,   OXPHOS↓, 1,   OXPHOS↑, 2,   ROS?, 1,   ROS↓, 34,   mt-ROS?, 1,   mt-ROS↓, 2,   SIRT3↑, 3,   SOD↑, 14,   TBARS↓, 1,   TOS↓, 1,   Trx1↑, 2,   UCPs↑, 1,   uricA↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↓, 1,   ATP↑, 8,   compIII↑, 1,   DRP1/DNM1L↓, 1,   FIS1↓, 1,   Insulin↑, 1,   MMP↑, 40,   PGC-1α↑, 5,   PGC-1α↝, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACC↑, 1,   ALAT↓, 5,   AMPK↑, 3,   p‑AMPK↑, 2,   BMAL1↑, 1,   BUN↓, 1,   ECAR↓, 1,   glucose↓, 3,   glucose↝, 1,   GlucoseCon↑, 1,   Glycolysis↓, 1,   Glycolysis↑, 1,   KeyT↝, 1,   LDL↓, 2,   PPARα↑, 1,   PPARγ↑, 2,   SIRT1↑, 2,   SREBP1/SREBF1↑, 1,   STK11/LKB1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Akt↑, 3,   p‑Akt↑, 2,   APAF1↓, 1,   Apoptosis↓, 9,   mt-Apoptosis↓, 1,   BAX↓, 5,   Bax:Bcl2↓, 2,   Bcl-2↑, 3,   Casp12↓, 1,   Casp3↓, 9,   cl‑Casp3↓, 1,   Casp9↓, 3,   cl‑Casp9↓, 1,   Cyt‑c↓, 6,   Cyt‑c∅, 1,   GranB/GZMB↓, 1,   iNOS↓, 4,   p‑JNK↓, 1,   p‑JNK↑, 1,   MAPK↓, 2,   p38↓, 1,   TRPV1↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 2,   other↑, 3,   other↝, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 2,   p‑eIF2α↓, 1,   ER Stress↓, 1,   GRP78/BiP↓, 2,   HSP70/HSPA5↑, 1,   HSPs↑, 1,   XBP-1↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3II↑, 1,   p62↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 2,   cl‑PARP↓, 1,   PARP1↓, 1,  

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

Diff↑, 1,   ERK↑, 2,   p‑ERK↑, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↑, 1,   mTOR↓, 1,   PI3K↓, 2,   PI3K↑, 2,   p‑PI3K↑, 1,   STAT3↓, 1,  

Migration(tgid=13) ⓘ

APP↓, 1,   Ca+2?, 1,   Ca+2↓, 4,   Ca+2↑, 1,   i-Ca+2↓, 1,   CXCL12↑, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 2,   TGF-β↑, 1,   VCAM-1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1,   ATF4↓, 1,   Hif1a↑, 1,   NO↓, 3,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 5,   GastroP↑, 1,   IBI↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 2,   COX1↓, 1,   COX2/PTGS2↓, 6,   COX2/PTGS2↑, 1,   CRP↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IL10↑, 2,   IL17↓, 1,   IL18↓, 3,   IL1β↓, 8,   IL2↓, 1,   IL4↓, 1,   IL6↓, 6,   IL6↑, 1,   Imm↑, 2,   Inflam↓, 15,   LPS↓, 1,   pol-M2 MC↑, 1,   MCP1/CCL2↓, 1,   NF-kB↓, 6,   PAR-2↓, 1,   PGE2↓, 2,   TNF-α↓, 10,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↑, 1,   AChE↓, 6,   BChE↓, 2,   BDNF↑, 3,   NGF↑, 1,   p‑tau↓, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 10,   BACE/β-secretase↓, 2,   NLRP3↓, 2,   β-Amyloid↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 6,   BioAv↝, 3,   Dose⇅, 1,   Dose↝, 6,   eff↑, 8,   eff↝, 1,   Half-Life↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 5,   AST↓, 6,   BMD↑, 1,   creat↓, 4,   CRP↓, 1,   GutMicro↑, 4,   IL6↓, 6,   IL6↑, 1,   Urea↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 2,   AntiCan↑, 1,   AntiDiabetic↑, 1,   antiPs↑, 2,   AntiTum↑, 1,   ANXi↓, 1,   cardioP↑, 6,   chemoP↑, 1,   cognitive↑, 5,   hepatoP↑, 8,   memory↑, 7,   motorD↑, 3,   neuroP↑, 20,   Obesity↓, 2,   Pain↓, 1,   RenoP↑, 3,   toxicity↓, 4,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1,   AntiViral↑, 1,   Bacteria↓, 1,   CD8+↑, 1,   Sepsis↓, 1,  
Total Targets: 209

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential
5 Honokiol
5 Quercetin
5 Thymoquinone
4 Ginkgo biloba-EGb 761
4 Magnetic Fields
4 Taurine
3 Baicalein
3 Boron
3 Capsaicin
3 Resveratrol
3 Silymarin (Milk Thistle) silibinin
2 Silver-NanoParticles
2 Alpha-Lipoic-Acid
2 EGCG (Epigallocatechin Gallate)
2 Ferulic acid
2 Hydrogen Gas
2 isoorientin
2 Luteolin
2 Rosmarinic acid
2 Vitamin K2
1 Apigenin (mainly Parsley)
1 Astaxanthin
1 Baicalin
1 Beta-Caryophyllene
1 α-Bisabolol / Chamomile oil
1 Celastrol
1 Chrysin
1 Cichoric acid / Chicoric acid
1 Curcumin
1 Cyclopamine
1 Emodin
1 Electrical Pulses
1 Formononetin
1 Gossypol/AT-101
1 Cisplatin
1 doxorubicin
1 Inositol
1 isoquercitrin
1 Lycopene
1 Melatonin
1 Moringa oleifera
1 Propolis -bee glue
1 Rauwolfia serpentina/Indian Snakeroot
1 Ursolic acid
1 Urolithin
1 Vitamin B5,Pantothenic Acid
1 Vitamin C (Ascorbic Acid)
1 Vitexin
1 Isovitexin
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

 

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