NLRP3 Cancer Research Results
NLRP3, NOD-like receptor pyrin domain-containing protein 3: Click to Expand ⟱
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NLRP3 (NOD-like receptor pyrin domain-containing protein 3) is a protein that plays a crucial role in the regulation of inflammation and immune responses.
NLRP3 typically has high expression in cancers, with poor prognosis.
For alzheimer's disease:
-NLRP3 is upregulated in Alzheimer's disease (AD)
-NLRP3 is activated in microglia in response to amyloid-β (Aβ) and tau aggregates.
-Promotes tau hyperphosphorylation and spread via inflammation-driven pathways.
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Scientific Papers found: Click to Expand⟱
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*BioAv↑, become increasingly clear in the recent years that 1,8-Cineol spreads almost everywhere in the human body after its oral administration, from the gut to the blood to the brain.
*BBB↑,
*AntiViral↑, anti-viral effects have been observed to include numerous bacteria and fungi species.
*Bacteria↓,
*AntiFungal↑,
*Inflam↓, central mode of action of 1,8-Cineol is the inhibition of pro-inflammatory cytokine expression
*BioAv↑, 1,8-Cineol was detectable in nasal tissue samples after its oral administration for 14 days, which indicates the systemic distribution of 1,8-Cineol via the gut and the blood stream
*MUC2↓, significantly reduced expression levels of the mucin genes MUC2 and MUC19 in close association with a significantly attenuated activity of transcription factor NF-κB
*MUC19↓,
*NF-kB↓, reduced the expression levels of transcriptional activator nuclear factor (NF)-kB p65 and expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in lung tissues
*ICAM-1↓,
*VCAM-1↓,
DNAdam↑, colon cancer cells on the potential genotoxicity of 1,8-Cineol revealed a concentration-dependent increase in oxidative DNA damage, whereas it did not affect the cell viability due to DNA repair mechanisms
*lipid-P↓, suppressing the expression of lipid mediators and prostaglandin D2
*PGE2↓,
*IL4↓, decreased expression levels of different inflammatory cytokines such as interleukin (IL)-4, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF) in bronchial epithelial cells
*IL6↓,
*IL1β↓, 1,8-Cineol-containing leaf extracts significantly suppressed the expression of pro-inflammatory cytokines IL-1β and IL-6 [
*IL6↓,
eff↑, 1,8-Cineol in combination with ellagic acid has been shown to downregulate different cytokines such as transforming growth factor beta-1 (TGF-β1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in p
TGF-β↓,
fascin↓,
VEGF↓,
MMP9↓,
*MAPK↓, 1,8-Cineol was shown to suppress the activation of the MAPK/ERK
*ERK↓,
JNK↓, decreased activities of transcription factor NFκB and the JNK (c-Jun N-terminal kinase)/AP-1 (activator protein-1) pathway in the human cancer cell lines U373 and HeLa in response to 1,8-Cineol, the active ingredient of the drug Soledum
Wnt↓, 1,8-Cineol acts as an inhibitor of the Wnt/β-catenin pathway in head and neck squamous cell carcinoma (HNSCC).
β-catenin/ZEB1↓,
GSK‐3β↑, decreased inhibition of glycogen synthase kinase 3 (GSK-3) and reduced levels of WNT11
*neuroP↑, 1,8-Cineol has been shown to have neuroprotective activity.
*GSK‐3β↓, decreased activity of GSK-3 in response to 1,8-Cineol could ameliorate advanced glycation end products,
*AGEs↓,
*BBB↑, eucalyptol reveals an opening effect on the blood–brain barrier
*NLRP3↓, controls inflammation by suppressing the NOD-like receptor pyrin domain-containing 3 (NLRP3) activation
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HK2↓, Two commonly used inhibitors, 2-Deoxy-D-glucose (2-DG) and 3-BrPA, have also been discovered
NF-kB↓,
NLRP3↓, Knockdown of HK in previous study inhibits activation of NLRP3 by extracellular ATP
*ROS↓, Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects
*Inflam↓,
*NLRP3↓, Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB
*NF-kB↓,
*NRF2↑, by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway
*HO-1↑,
*toxicity↓, Several studies have reported that Se was capable of protection against the toxicity of heavy metals, including its role against AgNP-induced toxication.
*TNF-α↓, Allicin treatment reduced TNF-α, IL-1β, IL-6, ROS levels, and the expression of NLRP3 and TLR4 proteins in mice with CCI, while IL-4 and IL-10 levels remained unchanged.
*IL1β↓,
*IL6↓,
*ROS↓,
*NLRP3↓,
*TLR4↓,
*PKCδ↑, allicin increased PKC-δ expression and PLS3 phosphorylation in the CL-related mitophagy process in both the CCI and Bv2 cell stretch models.
neuroP↑, allicin reduces mitophagy-related neuroinflammation and further prevents neuronal injury in vitro.
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*neuroP↑, Apigenin, a flavonoid found in various herbs and plants, has garnered significant attention for its neuroprotective properties
*antiOx↑, shown to possess potent antioxidant activity, which is thought to play a crucial role in its neuroprotective effects
*ROS↓, Apigenin has been demonstrated to scavenge ROS, thereby reducing oxidative stress and mitigating the damage to neurons
*Inflam↓, apigenin has been found to possess anti-inflammatory properties.
*TNF-α↓, inhibit the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, which are elevated in neurodegenerative diseases
*IL1β↓,
*PI3K↑, apigenin has been shown to activate the PI3K/Akt signaling pathway, which is involved in promoting neuronal survival and preventing apoptosis.
*Akt↑,
*BBB↑, Apigenin has additional neuroprotective properties due to its ability to cross the BBB and enter the brain
*NRF2↑, figure 1
*SOD↑, pigenin has also been shown to activate various antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)
*GPx↑,
*MAPK↓, Apigenin inhibits the MAPK signalling system, which significantly reduces oxidative stress-induced damage in the brain
*Catalase↑, , including SOD, catalase, GPx and heme oxygenase-1 (HO-1) [37].
*HO-1↑,
*COX2/PTGS2↓, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*PGE2↓,
*PPARγ↑, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*TLR4↓,
*GSK‐3β↓, Apigenin can inhibit the activity of GSK-3β,
*Aβ↓, Inhibiting GSK-3 can reduce Aβ production and prevent neurofibrillary disorders.
*NLRP3↓, Apigenin suppresses nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation by upregulating PPAR-γ
*BDNF↑, Apigenin causes upregulation of BDNF and TrkB expression in several animal models
*TrkB↑,
*GABA↑, Apigenin enhances GABAergic signaling by increasing the frequency of chloride channel opening, leading to increased inhibitory neurotransmission
*AChE↓, It blocks acetylcholinesterase and increases acetylcholine availability.
*Ach↑,
*5HT↑, Apigenin has been shown to increase 5-HT levels, decrease 5-HT turnover, and prevent dopamine changes.
*cognitive↑, Apigenin increases the availability of acetylcholine in the synapse after inhibiting AChE, thereby enhancing cholinergic neurotransmission and improving cognitive function and memory
*MAOA↓, apigenin acts as a monoamine oxidase (MAO) inhibitor and MAO inhibitors increase the levels of monoamines in the brain
*ROS↓, Artemisitene inhibits ROS (especially mtROS) production and NLRP3 inflammasome assembly.
*NLRP3↓,
*Inflam↓, artemisitene significantly attenuated inflammatory response in DSS-induced ulcerative colitis
*hepatoP↑, Withania Somnifera, is a hepatoprotective agent
*IKKα↓, WA also inhibits inflammation by directly inhibiting IκκB activity46,47 or NLRP3 inflammasome activation in vitro in immune cells
*NLRP3↓,
*NRF2↑, WA probably protects against FH by targeting the macrophage and/or hepatocyte stress via activating NRF2, AMPKα
*AMPK↑,
*Inflam↓, Thus, WA potently protects against GalN/LPS-induced hepatotoxicity and inflammation
*Apoptosis↓, WA suppressed hepatic apoptosis in vivo
*cl‑Casp3↓, attenuate the increase of cleaved CASP3 and cleaved PARP1
*cl‑PARP1↓,
*NLRP3↓, WA prevented GalN/LPS-induced FH partially by inhibiting activation of the NLRP3 inflammasome
*ROS↓, fig 7
*ALAT↓,
*AST↓,
*GSH↑, (GSH) levels were significantly depleted by ~50% 6 h after GalN/LPS administration and were recovered to levels comparable with that of control mice by WA treatment
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*neuroP↑, Recent studies have shown its good protective effect on neurons and brain tissues [14].
*antiOx↑, strong anti-inflammatory and antioxidant properties.
*Inflam↓,
*BioAv↝, When taken orally, baicalin is converted to baicalein via β-glucuronidase (GUS), which is produced by the intestinal flora.
*BioAv↑, Pharmacokinetics indicate that baicalein has a higher absorption rate than baicalein [19], but once it is absorbed, baicalein is quickly degraded in the bloodstream, yielding baicalein
*Half-Life↝, The distribution half-life and elimination half-life of baicalin in the CSF of normal rats are 0.8868 and 26.0968 min, respectively.
*TLR4↓, Inhibition of the TLR4/MyD88/NF-κB signal
*NF-kB↓,
*iNOS↓, decreasing the synthesis of iNOS, COX2, and TNF-α
*COX2/PTGS2↓,
*TNF-α↓,
*12LOX↓, downregulation of 12/15-LOX after cerebral ischemia
*NLRP3↓, Inhibition of the expression of NLRP3, HT-22 cells
*ROS↓, Decrease in the ROS levels in the ICH, thus inhibiting high NLRP3
*IL1β↓, Reduced the amounts of IL-1β and IL-6 and inhibited the activation of the NLRP3 inflammasome
*IL6↓,
*GSK‐3β↓, Inhibiting the activation of the GSK3β/NF-κB/NLRP3 signaling pathway
*NRF2↑, Fang et al. reported that the activation of the Akt pathway resulted in increased Nrf2 nuclear translocation and immunoreactivity in a group treated with baicalin
*BBB↑, baicalein effectively crosses the blood‒brain barrier (BBB) and stimulates the Nrf2/HO-1 pathway via specialized brain-targeted exosomes
*SOD↑, increased serum levels of SOD and GSH-Px.
*GPx↑,
*MDA↓, baicalin inhibited the ROS production and reduced MDA levels in brain tissues from a rat model of cerebral I/R injury induced by middle cerebral artery occlusion (MCAO).
*MMP↓, BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides.
*ROS↑,
*BloodF↑, while improving blood flow
*Pain↓, CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats.
*antiOx↑,
*Inflam↓,
*AMPK↑, in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions
*SIRT3↑,
*NRF2↑,
*PINK1↑,
*PARK2↑,
*LC3B↑,
*Beclin-1↑,
*TFAM↑,
*NLRP3↓, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted
*NF-kB↓,
*COX2/PTGS2↓,
*p62↓,
*NP/CIPN↓, CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system.
*cognitive↑, highlights β-caryophyllene's ability to mitigate key contributors to sleep loss-induced cognitive impairment, such as inflammation, oxidative stress, neuronal death, and reduced neuroplasticity
*Inflam↓,
*ROS↓,
*TLR4↓, by modulating various signaling pathways, including TLR4/NF-κB/NLRP3, MAPK, Nrf2/HO-1, PI3K/Akt, and cAMP/PKA/CREB.
*NF-kB↓,
*NLRP3↓,
*MAPK↓,
*NRF2↑,
*HO-1↑,
*PI3K↑,
*Akt↑,
*cAMP↑,
*PKA↑,
*CREB↑,
NLRP3↓, Establishing the Importance of Boron in 2APB for NLRP3 Inflammasome Inhibition
GutMicro↑, Butyrate, a short-chain fatty acid, is generated through gut microbial fermentation of dietary fiber.
*Inflam↓, Butyrate, a primary anti-inflammatory SCFA, exhibits a multifaceted role in mitigating inflammation
*IL6↓, It inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, TNF-α and IL-17, which helps to prevent colon cancer
*TNF-α↓,
*IL17↓,
*IL10↑, while promoting IL-10 production
*ROS↝, regulates the production of reactive oxygen species (ROS)
COX2/PTGS2↓, butyrate has been observed to suppress inflammation by inhibiting the expression of cyclooxygenase-2 mRNA in colonic tissues (60).
NLRP3↓, butyrate exhibits the highest efficiency in the negative regulation of NLRP3
Imm↑, Enhancement of the immunotherapeutic effect
HDAC↓, Inhibition of HDAC activity in cells
TumCCA↑, Butyrate has been found to induce cell cycle arrest in the G0/G1 phase in a dose-dependent manner in vitro in numerous tumors, including colon, liver, lung and bladder cancer,
Apoptosis↑, butyrate-induced apoptosis is accompanied by elevated ROS levels and caspase activity (126)
ROS↑,
Casp↑,
mtDam↑, suggests that ROS can induce mitochondrial membrane damage, release Cyt c from damaged mitochondria, and enhance apoptosis via the Cyt c/caspase-3 pathway
Cyt‑c↑,
eff↑, Clostridium butyricum is an anaerobic bacterium classified as a probiotic due to its production of butyric acid (139)
chemoP↑, butyrate not only alleviates the side effects associated with conventional chemotherapeutic agents such as oxaliplatin, irinotecan and 5-fluorouracil (149-151), but it also enhances the efficacy of both chemotherapy and immunotherapy
ChemoSen↑,
eff↑, metformin has been demonstrated to enhance the biosynthesis of butyrate while concurrently inhibiting the progression of CRC
RadioS↑, Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone.
HCAR2↑, Activation of cell-surface receptors (GPR41, GPR43 and GPR109A);
*neuroP↑, neuroprotective effect of CA on neuronal cells subjected to ischemia/hypoxia injury via the scavenging or reduction of ROS (reactive oxygen species) and NO (nitric oxide) and inhibition of COX-2 and MAPK pathways
*ROS↓,
*NO↓,
*COX2/PTGS2↓,
*MAPK↓,
*NRF2↑, CA is known to activate the Keap1/Nrf2 pathway, thereby resulting in the production of cytoprotective proteins.
*GSH↑, activation of GSH metabolism
*HO-1↑, activation of Nrf2 target genes, including heme oxygenase 1 (HO-1) and thioredoxin reductase 1 (TXNRD1)
*5HT↑, Observations of increased serotonin and BDNF suggest that CA may represent a novel therapeutic avenue for depressive behaviors that should be further explored.
*BDNF↑, 10 μM CA results in a 1.5-fold increase in levels of BDNF
*PI3K↑, CA has been shown to mediate the activation of the PI3K/Akt/NF-κB pathway
*Akt↑,
*NF-kB↑,
*BBB↑, CA was shown to ameliorate brain edema and blood-brain barrier (BBB) disruption
*SIRT1↑, CA was also shown to increase SIRT1
*memory↑, CA was shown to significantly improve short-term and spatial memory attributes in rat models of AD
*Aβ↓, CA also delayed the deposition of Aβ and protected cells against Aβ-induced cholinergic and mitochondrial dysfunction in a Caenorhabditis elegans model of AD
*NLRP3↓, CA also inhibits the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, which plays a critical role in the pathogenesis of neurodegenerative disorders, including AD and PD and COVID-19
*Imm↑, CA enhances immune responses, reduces inflammation, exerts antimicrobial effects, and improves overall fish health.
*Inflam↓,
*Bacteria↓,
*eff↑, sustainable functional-feed strategies that diminish antibiotic reliance in aquaculture.
*ROS↓, Reduced MDA levels and ROS accumulation
*MDA↓,
*Catalase↑, Increased CAT, GSH, and T-AOC activities
*GSH↑,
*TAC↑,
*NF-kB↓, Suppressed the activation of the NF-κB signaling pathway and the NLRP3 inflammasome pathway in the gills
*NLRP3↓,
*eff↑, In rainbow trout (Oncorhynchus mykiss), co-supplementation with 1–3 g RA/kg and Lactobacillus rhamnosus yielded synergistic improvements in growth, antioxidant capacity, and stress tolerance
*AST↓, In rainbow trout, CinA (0.25–1.5 g/kg) lowered intestinal pH, serum triglycerides, and hepatic enzyme levels (AST and ALT), while upregulating hepatic antioxidant genes (SOD and GST) [49]
*ALAT↓,
*SOD↑,
*GSTA1↑,
*antiOx↑, Carnosic acid (CA) has been reported to possess antioxidative properties
*Weight↑, CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS).
*p65↓, CA decreased the activation of p65 and c-Jun signalling.
*cJun↓,
*NLRP3↓, CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity.
*Casp1↓,
*NRF2↑, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1,
*GSH↑, Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced.
*SOD↑,
*MDA↓,
*iNOS↓,
other↝, Moreover, many compounds from natural products, such as ellagic acid, gallic acid and quercetin, have been shown to prevent IBD through their antioxidative properties
AntiCan↑, xhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc.
BioAv↓, However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application.
Apoptosis↑, i) induced apoptosis and autophagy
TumAuto↑,
TumCCA↑, ii) cell cycle arrest
TumMeta↓, iii) antimetastatic and anti-angiogenic actions
angioG↓,
Inflam↓, iv) anti-inflammatory effects
antiOx↑, Ⅴ) antioxidant activities
ChemoSen↑, For a rational design to achieve optimal efficacy and reduce their toxicity, combination strategies used are essential
HSP90↓, celastrol not only induced the expected ubiquitinylation and degradation of ErbB2 and other HSP90 client proteins, but it also increased the levels of ROS
ROS↑,
RadioS↑, celastrol may be considered an effective radiosensitizer acting as an inhibitor of Hsp90 and a p53 activator.
P53↑,
NLRP3↓, Lee et al. introduce celastrol, as an inhibitor of NLRP3 infammasome,
*BioAv↓, CGA’s oral bioavailability remains limited, prompting research into optimized extraction methods, novel formulations, and structural modifications.
*antiOx↑, antioxidant, anti-inflammatory, anticancer, antibacterial, hepatoprotective, cardioprotective and neuroprotective effects, and modulation of lipid and glucose metabolism
*Inflam↓,
*Bacteria↓,
*hepatoP↑,
*cardioP↑,
*neuroP↑,
*ROS↓, CGA action include inhibition of oxidative stress, regulation of inflammatory responses through modulation of the NF-κB pathway and activation of the Nrf2 pathway
*NF-kB↓, inhibition of NF-κB
*NRF2↑,
*Obesity↓, Research demonstrates that CGA may influence body weight regulation through multiple pathways, including modulation of gut microbiota, reduction of inflammation, regulation of adipogenesis, and stimulation of thermogenesis.
*GutMicro↑, increasing the abundance of probiotic bacteria such as Bifidobacterium and Lactobacillus, while reducing the abundance of bacterial strains found in obese patients and animals, such as Desulfovibrionaceae, Ruminococcaceae, Lachnospiraceae, and Erysip
*AntiAg↑, antiplatelet effects of CGA are supported by both in vitro and in vivo studies
*cardioP↑, CGA was recognized as a compound with high cardioprotective potential, considering its antioxidant, anti-inflammatory, and antihypertensive activities
*AntiDiabetic↑, CGA alleviates the effects of type 2 diabetes mellitus (DM) and helps prevent its development
*NLRP3↓, CGA also inhibits the NLRP3 inflammasome via Nrf2 activation, significantly decreasing proteinuria, creatinine, and urea levels in diabetic rats
*OCLN↓, figure 3
*VEGF↓,
BioAv↝, CGA is water-soluble but highly unstable when exposed to elevated temperature, light, oxygen, or alkaline pH
PKM2↓, Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation
Glycolysis↓,
NLRP3↓,
Inflam↓, Anti-inflammatory effect of chlorogenic acid is mediated through PKM2-dependent glycolysis
HK2↓, hexokinase 2 (Hk2), pyruvate dehydrogenase kinase 1 (Pdk1) and lactate dehydrogenase A (Ldha), while CGA significantly decreased this up-regulated genes level in macrophages
PDK1↓,
LDHA↓,
GLUT1↓, significant reduction in the LPS-induced increased glucose transporter protein 1 (Glut1) mRNA
ECAR↓, Importantly, the enhanced extracellular acidification rates (ECRA), indicative of glycolysis, was rescued by CGA treatment
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TumCI↓, Under the action of Crocin, EdU positivity rate, colony formation number, wound healing rate, and number of invaded cells were significantly reduced, while apoptosis rate increased.
Apoptosis↑,
TLR4↓, Crocin downregulated TLR4, p-NF-κB p65, p-IκBα, and NLRP3, inhibiting TLR4/NF-κB pathway and NLRP3.
NF-kB↓,
IKKα↓,
NLRP3↓,
TumCG↓, Crocin inhibited tumor growth in vivo, and the changes of TLR4/NF-κB pathway and NLRP3 related proteins levels were consistent with those in vitro.
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*toxicity↑, The emergence of natural products has provided extremely valuable references for the treatment of various diseases. Cucurbitacin B, a tetracyclic triterpenoid compound isolated from cucurbitaceae and other plants, is the most abundant member of the c
*antiOx↑, cucurbitacin B and cucurbitacin I have antioxidant properties, which can inhibit lipid peroxides
*Inflam↓, These results suggest that cucurbitacin B can inhibit the activation of NLRP3 inflammasome to inhibit the inflammatory response and cell damage in brain I/R injury.
*NLRP3↓,
*NF-kB↓, cucurbitacins B, E, and I can significantly reduce the activation activity of NF-κB induced by TLR 2/4 agonists in cells.
*neuroP↑, administration of cucurbitacin B has been shown to enhance the generation of new neurons in the hippocampus of ICR and APP/PS1 mice, thereby ameliorating the working memory deficits observed in these mice models
*memory↑,
*GABA↑, Concurrently, cucurbitacin B enhanced the levels of GABA.
*cardioP↑, cucurbitacin B exerts protective effects on the heart, including the prevention of hypertrophy, the amelioration of compromised cardiac function following myocardial infarction,
AntiTum↑, Cucurbitacin B has cytotoxic activity on a variety of tumor cells (Figure 5), and it has a good clinical application prospect as an antitumor drug.
p‑FAK↓, cucurbitacin B inhibited the phosphorylation of FAK and paxillin, and it could also induce the production of reactive oxygen species (ROS), which is helpful for the anti-metastatic potential of the cells.
ROS↑,
TumMeta↑,
TumCP↓, cucurbitacin B induced early apoptosis in these cells and altered the expression of proteins involved in proliferation and apoptosis, such as up-regulating the p53 and p21 genes.
Apoptosis↑,
P53↑,
P21↑,
TumCCA↑, cucurbitacin B affected the cell cycle transition from the G0/G1 phase to the S phase.
p27/CDKN1B↑, cucurbitacin B upregulated the expression of p27 and downregulated the expression of CDK4, CDK2, cyclin D1, and cyclin E mRNA.
CDK4↓,
CDK2↓,
cycD1/CCND1↓,
cycE/CCNE↓,
STAT3↓, inhibiting the STAT3 signaling pathway
ChemoSen↑, combination of cucurbitacin B and cisplatin (DDP) enhanced the activation of caspase-3 and the cleavage of caspase-3 substrate PARP, and it decreased the expression level of pSTAT3.
MMP2↓, It may down-regulate the expression of MMP2, MMP9, and VEGF, which could significantly inhibit cell migration and angiogenesis.
MMP9↓,
VEGF↓,
TumCMig↓,
angioG↓,
NOTCH↓, the Notch signaling pathway in LNCaP cells was down-regulated.
EMT↓, Additionally, it inhibits the epithelial–mesenchymal transition (EMT) mediated by TGF-β1
toxicity↑, Cucurbitacin B exhibits good activity against HepG2 cells, but its high toxicity results in a low therapeutic index (TI).
BioAv↑, Cu-B SLNs can passively target tumors with the EPR effect and show higher accumulation in tumor interstitial space, which can improve the efficacy of cucurbitacin B and reduce the dose.
EPR↑,
*antiOx↑, Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties
*Inflam↓,
*AntiAge↑, Its potential anti-aging properties are due to its power to alter the levels of proteins associated with senescence, such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and sirtuins
*AMPK↑,
*SIRT1↑,
*NF-kB↓, preventing pro-aging proteins, such as nuclear factor-kappa-B (NF-κB) and mammalian target of rapamycin (mTOR)
*mTOR↓,
*NLRP3↓, Moreover, curcumin, by inhibiting the NF-κB pathway, can directly restrain the assembly or even inhibit the activation of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome
*NADPH↓, by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and elevating the activity of antioxidant enzymes and consequently lowering reactive oxygen species (ROS)
*ROS↓,
*COX2/PTGS2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1/CCL2↓,
*IL1β↓, by decreasing IL-1β, IL-17, IL-23, TNF-α, and myeloperoxidase, enhancing levels of IL-10, and downregulating activation of NF-κB
*IL17↓,
*IL23↓,
*TNF-α↓,
*MPO↓,
*IL10↑,
*lipid-P↓, curcumin showed a significant decline in lipid peroxidation and increased superoxide dismutase levels, in addition to a reduction in Aβ aggregation and tau hyperphosphorylation through the regulation of GSK3β, Cdk5, p35, and p25
*SOD↑,
*Aβ↓,
*p‑tau↓,
*GSK‐3β↓,
*CDK5↓,
*TXNIP↓, Curcumin also has an inhibitory role on the thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway
*NRF2↑, well as upregulation of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), HO-1, and γ-glutamyl cysteine synthetase (γ-GCS) in brain cells.
*NQO1↑,
*HO-1↑,
*OS↑, significant improvement in OS, and a positive evolution in memory and spatial learning
*memory↑,
*BDNF↑, Besides that, it promoted neurogenesis through increasing brain-derived neurotrophic factor (BDNF) levels
*neuroP↑, Curcumin can promote neuroprotection
*BACE/β-secretase↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.
*COX2/PTGS2↓, Curcumin downregulates the cyclooxygenase-2 (COX-2) pathway, reducing the production of prostaglandins associated with inflammation
*Inflam↓,
*5LO↓, directly inhibits lipoxygenase (LOX)
*NO↓,
*NF-kB↓,
*TNF-α↓,
*IL1↓,
*IL2↑,
*IL6↓,
*IL8↓,
*IL12↓,
*MCP1/CCL2↓,
*PGE2↓,
*MMP2↓,
*MMP3↓,
*MMP9↓,
*NLRP3↓,
*ROS↓, arthritis(basically normal cell)
| - |
in-vitro, |
Nor, |
NA |
|
|
|
- |
in-vivo, |
Nor, |
NA |
|
|
|
*RenoP↑, EGCG improved kidney function, reduced albuminuria and body weight, and alleviated renal pathological damage.
*NLRP3↓, EGCG treatment reduced the expression of the NLRP3 inflammasome and its associated proteins, including TXNIP, ASC, caspase‐1, and IL‐1β, as well as the levels of ROS and inflammatory factors such as TNF‐α, IL‐6, and IL‐18.
*TXNIP↓,
*ASC↓,
*Casp1↓,
*IL1β↓,
*ROS↓,
*TNF-α↓,
*IL6↓,
*IL18↓,
*Casp1↓, EGCG blocked MSU crystal-induced production of caspase-1(p10) and interleukin-1β in primary mouse macrophages, indicating its suppressive effect on the NLRP3 inflammasome.
*NLRP3↓,
*Inflam↓, contributing to the prevention of gouty inflammation
*antiOx↑, bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular protective, metabolic regulatory, neuroprotective, gut microbiota-modulating, and antimicrobial properties.
*Inflam↓,
*AntiCan↑,
*cardioP↑,
*neuroP↑,
*GutMicro↑,
*AntiBio↑,
*ROS↓, Figure 1, anti inflammatory
*TNF-α↓,
*IL6↓,
TumCP↓,
*LDL↓, cardioprotective
*NO↓,
*Obesity↓, Metabolic syndrome
*p‑tau↓, nervous system
*Aβ↓,
*NRF2↑, , EGCG has been shown to activate the Keap1/P62/Nrf2 signaling pathway,
*SOD↑, upregulation of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, indirectly diminishing the levels of intracellular oxygen free radicals
*Catalase↑,
*GPx↑,
*NLRP3↓, EGCG also restores autophagy levels, suppresses the activation of the NLRP3 inflammasome by inhibiting the mammalian target of rapamycin signaling pathway
*mTOR↓,
TumCCA↑, Cancer: induce cell cycle arrest and inhibit tumor cell proliferation
NRF2↓, EGCG inhibits CCL5-stimulated lung cancer cell proliferation by down-regulating Nrf2 expression
Apoptosis↑, Inducing Apoptosis in Cancer Cells
SIRT1↓, EGCG activates the mitochondrial apoptotic pathway by downregulating SIRT1 expression to modulate the SIRT1-p53 axis
miR-25-5p↓, In breast cancer, EGCG induces apoptosis by inhibiting miR-25 expression and elevating PARP, pre-caspase-3 and pre-caspase-9 protein levels
PARP↑,
Casp3↑,
Casp9↑,
ER Stress↑, in multiple myeloma, EGCG promotes apoptosis by activating the endoplasmic reticulum stress pathway
TumAuto↑, EGCG induces autophagic cell death in breast cancer cells by retaining YAP1 in the cytoplasm and promoting the assembly of the CHMP2B-VPS4B complex
EMT↓, EGCG has been demonstrated to inhibit EMT, invasion, and migration by blocking the TGFβ/Smad signaling pathway
TumCI↓,
TumCMig↓,
TGF-β↓,
Smad1↓,
STAT3↓, EGCG can directly bind to STAT3, reducing nuclear localization and inhibiting the transcription of PLXNC1.
VEGF↓, widely believed that EGCG can block this process by reducing the expression of vascular endothelial growth factor, a key factor in angiogenesis,
angioG↓, The inhibition of angiogenic mimicry by EGCG through the Twist/VE-calmodulin/AKT pathway has also been demonstrated in prostate cancer cells
Imm↑, Acting as an Immunomodulator
EGFR↓, EGCG possesses the ability to interact with EGFR and inhibit activity, strengthening the anticancer evidence for EGCG
*GutMicro↑, EGCG can regulate the balance of gut flora. For example, EGCG can inhibit the growth of harmful bacteria such as Escherichia coli and Salmonella, while promoting the proliferation of probiotics like Bifidobacterium and Lactobacillus
*Bacteria↓, Antibacterial and Antiviral Properties of EGCG
*AntiViral↑,
*BioAv↓, EGCG, its low bioavailability in the human body limits clinical efficacy.
*BioAv↑, Nanotechnology strategy of EGCG.
*eff↑, Co-encapsulation assay of EGCG with quercetin shows that the two synergistically enhanced the antioxidant capacity of EGCG
*BioAv↑, Combining EGCG with resveratrol increases its solubility and significantly improves its absorption in the small intestine.
eff↑, combination of EGCG and curcumin inhibits the activity of metabolic enzymes, reduces the rate of metabolism in the liver and enhances its antitumor efficacy
ChemoSen↑, synergistic effects of EGCG combined with chemotherapeutic agents such as 5-fluorouracil, celecoxib, cisplatin, and tamoxifen have also been reported
*toxicity↝, The European Food Safety Authority notes in scientific opinion that daily oral doses of 800 mg or higher of EGCG represent a common starting point for observed cases of liver injury
*Inflam↓, Emodin has a variety of pharmacological effects, including anti-inflammatory, anti-tumor, antibacterial, immune enhancement, lipid-lowering, blood glucose-lowering, kidney protection, etc.
*AntiTum↑,
*Bacteria↓,
*Imm↑,
*glucose↓,
*RenoP↑,
*TLR4↓, i.p 40 mg/kg Inactivating the TLR4/MyD88/NF-κB/NLRP3 pathway
*MyD88↓,
*NLRP3↓,
*NF-kB↓, 20 μM Inhibiting ROS-mediated NF-κB activation
*PI3K↓, Inhibiting the PI3K/mTOR/GSK3β signaling pathway
*mTOR↓,
*GSK‐3β↓,
*Hif1a↓, LPS-induced acute lung injury (ALI) in rats oral 20 mg/kg, 40 mg/kg Inhibiting the mTOR/HIF-1α/VEGF signaling pathway
*VEGF↓,
*GutMicro↑, oral 8.75, 17.5 and 35 mg/kg Increasing the abundance of beneficial intestinal microbiota and inhibiting the abundance of harmful bacteria
*Obesity↓, Similarly, in high-fat diet-induced obese mice, treatment with emodin (80 mg/kg) reduced body weight
*AntiDiabetic↑, emodin also has a good therapeutic effect on diabetic neuropathic pain (DNP), diabetic cardiomyopathy (DCM), and diabetic gastroenteropathy.
*AMPK↑, Emodin upregulates AMPK phosphorylation, downregulates mTOR phosphorylation, and reduces the expression of Bcl-2-associated X protein (Bax) and cysteine-dependent aspartate-specific proteases-3 (caspase-3), indicating that emodin actively regulates a
*PPARγ↑, Most current research results indicate that emodin has the effect of activating PPARγ in a dose-dependent manner
*PPARγ↓, however, the research results of Yang et al. showed that emodin can reduce the expression of PPARγ and enhance the expression of Runx2 and OSX, thereby enhancing the differentiation into osteoblasts
*toxicity↝, Although emodin has shown hepatoprotective effects in many studies, Zheng et al. showed hepatotoxicity when a large concentration of emodin (160 μM) was administered to L02 cells,
*hepatoP↑, whereas hepatoprotective effects were observed when emodin concentrations were controlled at 10–80 μM
*AST↓, the liver function test results showed that emodin at doses of 40 mg/kg and 80 mg/kg had a better effect on reducing AST and ALT than 160 mg/kg
*ALAT↓,
*Inflam?, Emodin is a bioactive phytochemical with potent multimodal anti-inflammatory, antioxidant, and antifibrillogenic properties.
*antiOx↑,
*tau↓, While emodin effectively prevents tau and amyloid-beta (Aβ) oligomerization, it also mitigates their neurotoxicity by attenuating neuroinflammatory, oxidative, and bioenergetic defects.
*Aβ↓,
*neuroP↑, In recent years, several studies have advocated for a robust neuroprotective function of emodin
*ROS↓,
*memory↑, Evidences for emodin-mediated enhancements in memory, learning, and cognition were also found in the literature
*cognitive↑,
*other↝, Well-known sources of emodin include Rheum palmatum,10Polygonum cuspidatum,11Aloe vera,12Polygonum multifarum,13 and Casia obtusofolia.
*AChE↓, potent in vitro inhibition of AChE (IC50 of 21.8 μM), in addition to amelioration of H2O2-induced oxidative damage in PC12 cells
*BACE/β-secretase↓, potent inhibition of the activities of BACE-1 (IC50 of 4.5 μM) and AChE (IC50 of 9.7 μM); and strong and mixed-type inhibition for BACE-1 (Ki of 20 μM) in kinetic studies
*LC3II↓, Inhibition of autophagic (LC3-II and beclin-1)
*Beclin-1↓,
*p‑tau↓, 80 mg/kg/day for 2 weeks (intragastric administration) repression of the levels of BACE-1, Aβ species and phosphorylated-tau, stimulation of CREB signaling
*CREB↑,
*HNE↓, downregulation of Aβ and phosphorylated-tau levels, reduced oxidative damage and 4-HNE levels
*BioAv↓, Bioavailability of exogenously administered emodin suffers from some issues, including its weak intestinal absorption, high rate of elimination, and first-pass metabolism
*BioAv↝, bioavailability of orally supplemented emodin may show appreciable dependence on gender, given that there are four times higher plasma levels of emodin in male rats, compared to females after a single oral dosing of emodin at 8 mg/kg body weight.
*BioAv↑, pretreatment with stilbene glucosides from Radix Polygoni Multiflori prevents glucuronidation of emodin, and increases its plasma concentration upon oral administration
*BioAv↑, cotreatment with piperine was also found to inhibit glucuronide formation of orally administered emodin, while increasing the bioavailability of its free form
*BioAv↑, Nanoemulsification may also decreses the clearance of orally administered emodin, while increasing its brain distribution and bioavailability.
*BioAv↑, Lastly, treatment of emodin with sodium hydroxide to form its sodium salt may represent another strategy for improving the solubility and bioavailability of emodin
BioAv↑, ultrasound-sensitive emodin-containing lecithin-based nanoformulations squamous cell carcinoma FaDu and CAL-27 cells neck squamous cell carcinoma sonodynamic therapy-based beneficial actions
*HO-1↑, figure 3, neuroproctive
*PKCδ↑,
*Akt↑,
*NLRP3↓,
*NF-kB↓,
*TLR3↓,
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2/PTGS2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells
*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↑,
*neuroP↑, it seems to ameliorate AD pathology by preventing neurodegeneration in several brain regions;
*Aβ↓, it has been shown to inhibit Aβ oligomer aggregations and to exert antioxidant, anti-inflammatory, and anti-apoptotic effects
*antiOx↑,
*Inflam↓,
*ROS↓, ability of ferulic acid to prevent oxidative stress
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B),
*NLRP3↓, it also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), has been observe
*COX2/PTGS2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK?, inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK),
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen in a mouse model of hepatotoxicity by inhibiting the expression of toll like receptor 4 (TLR4),
*TLR4↓,
*PPARγ↑, ferulic acid upregulated PPARγ and Nrf2 expression in renal cells,
*NRF2↑,
*Fenton↓, Ferulic acid may also inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu),
*IronCh↑,
*MDA↓, a lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker
*HO-1↑, Ferulic acid has been found able to upregulate HO-1, thus increasing the production of bilirubin, which acts as an efficient ROS scavenger,
*Bil↑,
*GCLC↑, (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic acid
*GCLM↑,
*NQO1↑,
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*SOD↑, Indeed, it prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*Ca+2↓,
*lipid-P↓,
*PGE2↓,
*RenoP↑, Fucoidan exhibits significant anti-inflammatory effects in kidney protection.
*Inflam↓,
*antiOx↑, Antioxidant properties effectively reduce oxidative stress in renal tissues.
*ROS↓,
*BloodF↑, Enhances renal function by improving blood flow and diuresis.
*diuretic↑,
*BioAv↓, High-MW fucoidans often display stronger anticoagulant and viscosity-modulating effects. However, they may have limited oral bioavailability,
*BioAv↑, whereas low- to medium-MW fractions show improved tissue penetration, more favorable absorption, and can retain potent anti-inflammatory and anti-fibrotic activities, making them attractive for chronic kidney disease applications
*MAPK↓, (LMWF) has been reported in models of renal ischemia-reperfusion injury, where it inhibits the MAPK signaling pathway and subsequently reduces inflammation and fibrosis
*ERK↑, fucoidan can activate the ERK/MAPK signaling pathway, which plays a crucial role in preserving the endothelial glycocalyx in CKD
*NLRP3↓, fucoidan attenuates NLRP3 inflammasome activation and subsequent podocyte pyroptosis, ultimately leading to improved renal function and reduced inflammation in diabetic kidney disease (DKD)
*NRF2↑, By inhibiting ROS-generating systems (e.g., NADPH oxidase) and activating Nrf2-dependent transcription of antioxidant genes, fucoidan limits mitochondrial dysfunction and prevents oxidative injury to podocytes and tubular epithelial cells
*MDA↓, fucoidan nanoparticles significantly reduced levels of malondialdehyde (MDA), a marker of lipid peroxidation and oxidative stress, while simultaneously upregulating the levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx)
*SOD↑,
*GPx↑,
*Catalase↑, Altogether, fucoidan directly reduces renal oxidative stress by scavenging reactive oxygen species and upregulating endogenous antioxidant defenses (e.g., SOD, CAT, GPx) in tubular and glomerular cells, by suppressing upstream ROS generation
*lipid-P↓, fucoidan limits lipid peroxidation and DNA damage, thereby preserving podocyte integrity and tubular epithelial viability
*DNAdam↓,
*Fibrosis↓, Inhibition of fibrosis
*JAK2↓, fucoidan combats renal fibrosis is via the restriction of the JAK2/STAT3 signaling pathway.
*STAT3↓,
*uricA↓, By reducing serum uric acid levels, fucoidan significantly inhibits the activation of JAK2/STAT3, consequently decreasing the expression of key fibrotic markers such as collagen I and α-smooth muscle actin (α-SMA)
*COL1↓,
*α-SMA↓,
*SIRT1↑, fucoidan’s anti-fibrotic effects are further attributed to its activation of protective pathways such as Sirt-1, GLP-1R, and Nrf2/HO-1(
*HO-1↑,
*GLP-1R↑,
*HMGB1↓, Stimulating these protective pathways results in the inhibition of pro-fibrotic signaling cascades, including the HMGB1/RAGE/NF-κB/TGF-β1 pathway
*RAGE↓,
*NF-kB↓,
*TGF-β1↓,
*PI3K↓, Fucoidan also exhibits potential in curtailing the inflammatory processes associated with renal fibrosis through its inhibitory effects on the PI3K/Akt/NF-κB signaling cascade.
*Akt↓,
*GutMicro↑, research has elucidated the important role of gut microbiota in mediating the protective effects of fucoidan, suggesting that modulation of microbial communities may underlie its benefits in renal health
*SCFAs↑, Fucoidan’s positive impact on gut microbiota includes enhancing the production of short-chain fatty acids (SCFAs), especially butyrate, which are known to support gut integrity and overall health (
*Buty↑,
*IBI↑, Fucoidan's ability to enhance SCFA production has been linked to improved intestinal barrier integrity, a crucial factor in preventing the translocation of harmful substances into the bloodstream, which can exacerbate kidney injury
*TJ↑, Studies indicate that fucoidan can upregulate the expression of tight junction proteins, crucial for maintaining the integrity of the intestinal epithelium
*Dose↝, national approval in China for renal indications, indicate that fucoidan is generally safe at oral doses of 50–300 mg/day and up to 1–3 g/day in short‑ to mid‑term studies, with no major hematologic, hepatic, or renal toxicity reported.
TumCMig↓, Galloflavin treatment could significantly attenuate the malignant behavior of SW480 in the inflammatory microenvironment and inhibit the migration and invasion capabilities of SW480
TumCI↓,
NLRP3↓, Galloflavin could inhibit the malignant behavior of colorectal cancer cells by targeting NLRP3.
LDH↓, Galloflavin (Gal), an LDH-A/B inhibitor (Guo et al., 2014; Wendt et al., 2020), has been found to exert a certain role in inflammatory regulation
Inflam↓, Gal could inhibit the release of inflammatory factors. The levels of IL-6, TNF-α, and IL-1β were significantly downregulated,
IL6↓,
TNF-α↓,
IL1β↓,
*Inflam↓, Ginkgolide B (GB) is a potential anti-inflammatory compound that controls neuro-inflammation.
*cognitive↑, GB significantly decreased the intracellular pro-inflammatory cytokine levels in lipopolysaccharide-treated BV2 cells and improved cognitive behavior in SAMP8 mice.
*NLRP3↓, GB deactivated the NLRP3 inflammasome, and this effect was dependent on autophagy.
*neuroP↑, GB exerted a neuroprotective effect on the cognitive function of SAMP8 mice by suppressing the activation of NLRP3 inflammasome via autophagic degradation.
*Dose↝, 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes.
*Inflam↓, In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1.
*COX2/PTGS2↓,
*iNOS↓,
*NF-kB↓,
*MAPK?,
*HO-1↑,
*PGE2↓, Rat/saline administration 50 and 500 mg/kg extract oral or i.p. Reduced PGE2 serum levels
*TNF-α↓, 25, 50, 100 and 200 mg/kg extract oral Reduced carrageenan-induced paw volume, levels of PGE2, TNF, IL-6, IL-1β, IFNγ, MCP-1, MIP-2, RANTES, and MPO activity and NO levels
*IL6↓,
*IL1β↓,
*IFN-γ↓,
*MCP1/CCL2↓,
*MIP2↓,
*RANTES↓,
*MPO↓,
*NO↓,
*Stroke↓, Therefore, the authors of this study suggest a potential benefit of 6-shogaol for the prevention of stroke [51].
*BrainVol↑, The daily oral administration of 6-shogaol (5 and 20 mg/kg) resulted in protection against transient focal cerebral ischemia, as indicated by a significant reduction of brain infarct volume and production of malondialdehyde (MDA) and of ROS after MCA
*MDA↓,
*ROS↓,
*GSH↑, 6-shoagol treatment resulted in an increased amount of glutathione (GSH) in H2O2-induced HepG2 cells
*NRF2↑, As H2O2-triggered Nrf2 degradation was recovered by 6-shogaol,
*antiOx↑, 6-Shogaol exhibits a stronger antioxidative activity than its homologues
NLRP3↓, 6-shogaol (20 µM) effectively inhibited total protein levels of NLRP3 and pro-IL-1β after a combined LPS and ATP-activated protein up-regulation
HDAC1↓, The LPS-caused induction of HDAC1 protein levels was reduced by 6-shogaol
| - |
vitro+vivo, |
AML, |
THP1 |
|
|
|
- |
in-vitro, |
AML, |
AMJ13 |
|
|
|
- |
vitro+vivo, |
lymphoma, |
HBL |
|
|
|
TumCP↓, THP-1 and AMJ-13
TumAuto↑,
IL1↓, IL-1b
NLRP3↓,
Apoptosis↑,
mtDam↑,
P53↑,
LDH↓, ability of AgNPs in increasing of LDH release.
| - |
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.
*antiOx↑, Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent.
*Inflam↓,
*Apoptosis↓,
*Dose↓, It reaches a maximum level of about 0.78 mM (≈1.6 mg/L) at room temperature with a loss of about 2–5% per 3 min
*Dose↝, It is produced (and consumed) by bacteria of the gut microbiota .The most prominent bacterial phyla involved in this process are the Firmicutes and Bacteroidetes phyla, which include the anaerobic Clostridium species
*eff↑, hydrogen mixed with oxygen at a ratio of 96%-to-4%, known as the Hydrox gas mixture, was used by deep-sea divers to prevent decompression sickness and allow diving to depths of up to 500 m
*ROS↓, The antioxidant activity of H2 is based on two processes: a direct scavenging of the most toxic reactive oxygen and nitrogen species (ROS/RNS),
*RNS↓,
*NRF2↑, H2 activates the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, a key transcription factor involved in oxidative stress-related responses, including cytoprotective, antioxidant, and detoxifying enzymes such as HO-1
*HO-1↑,
*Fenton↓, removal of free heme and inhibition of the Fenton reaction
*NLRP3↓, the activation of the Nrf2 pathway has been shown to inhibit the NLRP3 (NLR family pyrin domain containing 3) inflammasome,
*NADPH↓, H2 suppresses the activation of the NADPH oxidase pathway and downregulates the expression of NOX2 and NOX4
*NOX4↓,
*NOX↓,
*MPO↓, H2 has been shown to reduce the overactivation of myeloperoxidase (MPO)
*NF-kB↓, would further suppress the NFκB
*TNF-α↓, figure 3
*IL6↓,
*IL1β↓,
*HMGB1↓,
*IL4↑,
*IL10↑,
*M2 MC↑, Additionally, H2 promotes the polarization of macrophages from the proinflammatory M1 type to the anti-inflammatory M2 type
*Treg lymp↝, It also inhibits Th2 responses, restores regulatory T cells (Treg), and, thus, normalizes an overactivated immune system
*Bcl-2↑, upregulate the antiapoptotic factors, including Bcl-2 and Bcl-xl.
*Bcl-xL↑,
*PI3K↑, phenomenon is likely facilitated by the activation of the PI3K/Akt and JAK2/STAT3 signaling pathways
*Akt↑,
*JAK2↑,
*STAT3↑,
*Dose↑, The consumption of certain prebiotics, especially those rich in dietary fiber, indigestible starches, and sugars (lactulose), has been demonstrated to enhance intestinal H2 production through the activity of intestinal flora
*CD4+↑, H2 increased the population of CD4+CD25+Foxp3+ Treg cells, which are often decreased in allergic rhinitis (AR)
*CD25+↑,
*FOXP3↑,
*MDA↓, H2 administration attenuated oxidative stress expressed as lower MDA and other lipid peroxidation markers along with an enhancement in the expression and activity of endogenous antioxidant enzymes such as SOD or CAT
*SOD↑,
*Catalase↑,
*Casp3↓, inhibition of proapoptotic processes like the caspase 3 and 9 pathways
*Casp9↓,
*TBARS↓, drinking of HRW by patients with asthma and COPD leads to an increase in blood oxygen saturation, vitamin E levels, along with lower oxidative stress markers such as thiobarbituric acid reactive substances (TBARS), MDA,
*SpO2↑,
*VitE↓,
*OS↑, COPD:In general, H2 administration has been found to lead to enhanced survival and reduced weight loss [110], improved lung function and static lung compliance, and decreased arterial blood pressure
*Weight↑,
*DNAdam↓, reduction in levels of oxidative DNA damage markers
*PGE2↓, H2 reduced elevated inflammatory markers, including IL-1β, IL-6, TNF-α, prostaglandin E2 (PGE2) [29,65,71,128,130], macrophage protein 1α 2 (MP1α), and monocyte chemoattractant protein-1 (MCP-1)
*MCP1/CCL2↓,
*lipid-P↓, Further, a reduction in oxidative stress markers such as lipid peroxidation and proapoptotic markers, including Bax and caspase-3, was observed.
*TumCP↓, H2-rich medium reduced the colony size and formation of tongue cancer cells and decreased proliferation in human fibrosarcoma and esophageal cancer cells, as well as A549 cells
*tumCV↓, decrease in cell viability, migration, and invasion
*TumCMig↓,
*TumCI↓,
TumW↓, A reduction in tumor weight and size, as well as a lower number of cells of squamous cell carcinoma, was revealed by animal studies.
TumVol↓,
selectivity↑, Notably, as previously reported, H2 administration exhibited no effect on healthy animals or non-cancerous cell lines
QoL↑, Patients reported improved quality of life with better physical status and fewer pulmonary symptoms
ChemoSen↑, In combination with conventional (such as cis-platin) and modern (including antibodies like nivolumab) therapeutics, H2 enhanced drug activity, resulting in enhanced outcomes and improved disease control
chemoP↑, and reduced side effects of the treatment, such as nephrotoxicity, weight loss, insomnia, pain, or hearing loss in the case of radiotherapy
radioP↑, radioprotective effects of H2 are primarily attributed to its hydroxyl radical scavenging activity
ROS↑, As indicated by Yang et al., the latter include the activation of the ROS/NLRP3/caspase-3/gasdermin D-mediated pyroptotic pathways
NLRP3↑,
Casp3↑,
VEGF↓, suppression of vascular endothelial growth factor (VEGF) expression
Wnt↓, H2 result in the suppression of the overactivated Wnt/beta-catenin signaling pathways, which further leads to suppression of tumor progression
β-catenin/ZEB1↓,
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*antiOx↑, antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level
*NRF2↑, activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes.
*HO-1↑,
*Inflam↓, hydrogen may prevent inflammation
*neuroP↑, prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer.
*cardioP↑,
*other↓, It also prevented ischemia-reperfusion (I/R) injury and stroke in a rat model
*ROS↓, H2 has been shown to exert its beneficial effects in various pathological conditions that involve free radicals and oxidative stress
*NADPH↓, figure 2, H2 Inhibits NADPH Oxidase Activity
*Catalase↑,
*GPx1↑,
*NO↓, H2 Indirectly Reduces Nitric Oxide (NO) Production
*mt-ROS↓, H2 Decreases Mitochondrial ROS
*SIRT3↑, In the kidneys, H2 suppressed the downregulated Sirt3 expression, which is the most abundant member of the sirtuin family, by reducing oxidative stress reactions
*SIRT1↑, In the liver, H2 elevated HO-1 to induce Sirt1 expression
*TLR4↓, H2 inhibits TLR4, which involves hyperglycemia in type 2 diabetes mellitus
*mTOR↓, For example, H2 inhibits mTOR, activates autophagy, and alleviates cognitive impairment resulting from sepsis
*cognitive↑,
*Sepsis↓,
*PTEN↓, It inhibits the activation of the PTEN/AKT/mTOR pathway and alleviates peritoneal fibrosis
*Akt↓,
*NLRP3↓, It also facilitates autophagy-mediated NLRP3 inflammasome inactivation and alleviates mitochondrial dysfunction and organ damage
*AntiAg↑, antiageing mechanism of H2 and the influence on ageing hallmarks are summarized in Figure 3.
*IL6↓, significantly suppressed inflammatory cytokines (IL-6, TNF-α, and IL-1β), MDA, and 8-OHdG, and improved memory dysfunction
*TNF-α↓,
*IL1β↓,
*MDA↓,
*memory↑,
*FOXO3↑, HRW can also upregulate Sirt1-Forkhead box protein O3a (FOXO3a
TumCG↓, H2 inhibits lung cancer progression
*LDL↓, Decreases oxidized LDL; improves HDL function
*neuroP↑, potential neuroprotective effects, attributed to its selective antioxidant and anti-inflammatory properties.
*antiOx↑,
*Inflam↓,
*ROS↓, potential of molecular hydrogen to attenuate oxidative stress,
*NADPH↓, via the inhibition of NADPH oxidase activity
*NRF2↑, it also enhances the endogenous defense system by modulating the Nrf2/ARE pathway.
*BBB↑, easily penetrate the blood–brain barrier
*IL1β↓, H₂ significantly reduces the release of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, NF-κB, and HMGB1,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*NLRP3↓, hydrogen can mitigate neuroinflammation by inhibiting the NLRP3 inflammasome pathway
*Sepsis↓, hydrogen intervention in sepsis models
*p‑mTOR↓, inhibits the phosphorylation level of mTOR (indicated by a decrease in the p-mTOR/mTOR ratio) while activating the AMPK s
*AMPK↑,
*SIRT1↑, hydrogen-rich water alleviates intestinal oxidative stress by upregulating the expression of SIRT1, Nrf2, and HO-1
*HO-1↑,
*Inflam↓, hydrogen inhalation exhibit anti-inflammatory and anti-oxidant effects in many studies.
*antiOx↑,
*NLRP3↓, decline of nucleotide-binding domain leucin-rich repeat and pyrin domain-containing protein 3 (NLRP3) was proved to inhibit memory impairment and Aβ deposition.4
*memory↑,
*Aβ↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway
*SIRT1↑,
*FOXO3↑,
*p‑p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*JNK↓,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling and protecting mitochondria.
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels, estrogen receptor (ER) β
*ER(estro)↑,
*BDNF↑, and the expression of brain-derived neurotrophic factor (BDNF),
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models.
*Inflam↓,
*NLRP3↓, hydrogen could inhibit the activation of NLRP3 inflammasome in AD brains
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a
*SIRT1↑,
*FOXO3↑,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling
*BDNF↑, by reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neurotrophic factor (BDNF),
*Inflam↓, anti-inflammatory and antioxidant activity
*antiOx↑,
*ROS↓, annihilating excess reactive oxygen species production and modulating nuclear transcription factor.
*other↝, H2 does not explode if it is <10% when mixed with air or O2
*NF-kB↓, H2-rich saline inhibited the activation of crucial inflammatory signaling pathway NF-κB and reduced serum IL-1β, IL-6, and TNF-α levels,
*IL2↓,
*IL6↓,
*TNF-α↓,
*HO-1↑, Studies have demonstrated that H2 administration increased the HO-1 expression
Apoptosis↑, Similarly, cell apoptosis and autophagy were significantly enhanced in A549 and H1975 lung cancer cell lines treated with different concentrations of H2 gas
TumAuto↑,
*Sepsis↓, sepsis-related organ injury models, H2 treatment significantly reduced the expression of caspase-1 in the damaged organ and the levels of IL-1β and IL-18 cytokines
*NLRP3↓, NLRP3, caspase-1, and the N-terminal of gasdermin D (GSDMD-N), were reduced after lung inflation with 3% H2,
Pyro↑, H2-rich water inhibited the proliferation of endometrial cancer cells by triggering the NLRP3 inflammasome/caspase-1 mediated classical pyroptosis pathway and activated the downstream proinflammatory cytokine IL-1β.
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models
*Inflam↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway which could play a role in anti-oxidative
stress,
*SIRT1↑,
*FOXO↑,
*mtDam↓, diminishing mitochondrial damage and acting as a neuroprotective agent, and neutralize ROS induced by Aβ
*neuroP↑,
*ROS↓,
*p38↓, hydrogen water
could suppress the activation of phospho-p38 and JNK
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels
*BDNF↑, reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neuro-trophic factor (BDNF)
*memory↑, Li et al.71 found that hydrogen-rich saline could reduce
learning and memory impairments and neural inflammation
which were induced by Aβ in rats
*lipid-P↓, Moreover, hydrogen-rich saline suppressed lipid peroxidation products, inflammatory factor like interleukin-6 and TNF-α, and the activation of astrocytes
*IL6↓,
*TNF-α↓,
*JNK↓, protective effect of hydrogen-rich saline may be due to inhibition of the activation of JNK
and NF-κB
*NF-kB↓,
*NLRP3↓, Hydrogen-rich water inhibit NLRP3, and weaken the oestrogen-ERβ-BDNF signalling pathway.
*Inflam↓, Hydrogen therapy AD: inflammation, energy regulation, prevents neuronal damage.
*neuroP↑,
*toxicity↓, Hydrogen therapy's low side effects make it a complement to AD treatment. Even at high concentrations, hydrogen gas is still non-toxic, and has been widely used in the diving field.
*antiOx↑, hydrogen’s role as a natural antioxidant,
*ROS↓, Hydrogen has been shown to mitigate the amount of ROS released from mitochondria, thereby reducing mitochondrial DNA peroxidation and inhibiting the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and I
*NLRP3↓,
*IL1β↓,
*mtDam↓, curtail mitochondrial damage, thereby bolstering ATP synthesis and fortifying the electron transport chain within mitochondria
*ATP↑,
*AMPK↑, activating AMPK and amplifying the downstream antioxidant response of forkhead box O3a (FOXO3
*FOXO3↑,
*SOD1↑, It elevates the levels of intracellular antioxidant enzymes, notably superoxide dismutase 1 (SOD1) and catalase (CAT), thereby serving as a neuroprotective agent that diminishes the risk and progression of AD
*Catalase↑,
*NRF2↑, Hydrogen slows AD progression by activating the cellular endogenous antioxidant system Nrf2;
*NO↓, Reduced inflammatory markers such as ROS, Nitric oxide (NO) and Malondialdehyde (MDA)
*MDA↓,
*lipid-P↓, drinking HRW significantly reduced lipid peroxidation in the brain of SAMP8 mice.
*memory↑, HRW inhibited the decline of learning and memory impairment
*ER(estro)↓, Decreased hormone levels, estrogen receptor (ER) β, and BDNF expression improve cognitive function in female transgenic AD mice.
*BDNF↑, upsurge in BDNF levels, which further ameliorated the cognitive impairments observed in mice affected by sepsis.
*cognitive↑,
*APP↓, The expression of APP, BACE1, and SAPPβ was proficiently suppressed, thereby curtailing the overproduction of Aβ in Alzheimer's
*BACE/β-secretase↓,
*Aβ↓,
*BP∅, inhaling hydrogen gas has no effect on blood pressure and other blood parameters (such as pH, body temperature, etc.),
*BBB↑, efficiently crossing the blood-brain barrier to perform their functions.
*APP↓, prevent the progress of the disease by affecting the amyloid precursor protein metabolism, anti-apoptosis, anti-inflammatory, and antioxidant pathways.
*Apoptosis↓,
*Inflam↓,
*antiOx↑,
*BP↓, H2S activates adenosine triphosphate-sensitive potassium channels, which in turn dilates blood vessels and lowers blood pressure, while improving myocardial ischemia-reperfusion injury
*NLRP3↓, activation of NLRP3 inflammatory bodies was inhibited
*ROS↓, catalase may be a key enzyme in the metabolism of H2S, which can convert H2S into sulfide, thereby achieving scavenging effect.
*Aβ↓, H2S can promote APP's non-amyloid metabolic pathway and reduce Aβ production.
*ER Stress↓, H2S may up-regulate brain-derived neurotrophic factor-TrkB pathway to suppress the stress of the endoplasmic reticulum,
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*RenoP↓, Thirdly, long-term use of hyperoside is toxic to the kidneys, but the damage is reversible
Casp3↑, Up-regulates caspase-3, caspase-8, Bax, p53 and MDA contents; decreases GSH, SOD and CAT activities; decreases VEGF and Bcl-2 levels; and inhibits cell growth. HeLa 100 μmol/L
Casp8↑,
MDA↑,
GSH↓,
SOD↓,
Catalase↓,
VEGF↓,
Bcl-2↓,
TumCG↓,
p‑Akt↓, Down-regulates BMP-7 expression, AKT phosphorylation and PI3K expression; induces cell cycle arrest; and inhibits cell proliferation. Human HepG2 5, 10, 20, 40 and 80 μM
PI3K↓,
TumCCA↑,
TumCP↓,
BMP7/OP1↓,
*ZO-1↑, up-regulates ZO-1 and claudin5 protein expression; maintains the integrity of the blood–brain barrier; and may protect neural function in CIR-injured mice. CIR injury induced by MCAO in mice 50 mg/kg
*BBB↝,
*p‑Akt↑, increases the phosphorylation of AKT and GSK-3β; alleviates early brain injury after subarachnoid haemorrhage; and promotes nerve function recovery in rats.
*GSK‐3β↑,
*SOD↑, increases SOD and CAT activities and GSH content; increases SIRT1 gene expression; down-regulates NF-κB mRNA
*Catalase↑,
*GSH↑,
*SIRT1↑,
*NF-kB↓,
*IL1β↓, Down-regulates IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax and caspase-3 levels; increases CAT, SOD and GSH activities; up-regulates Bcl-2, BDNF, TrkB, SIRT1 and NGF expression; reduces LPS-induced inflammation, oxidative stress and apoptosis; and protec
*IL6↓,
*IL8↓,
*TNF-α↓,
*ROS↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*Apoptosis↓,
*cardioP↑, Cardioprotective Activity of Hyperoside.
*AST↓, Decreases the levels of AST, CK, CK-MB and c-TnT in rats; the rate of cardiomyocyte apoptosis;
*hepatoP↑, Hepatoprotective Activity of Hyperoside.
*AST↓, Decreases liver index, AST, ALT, MDA and Bach1 complex levels and alleviates the pathological damage of acute liver injury mice.
*ALAT↓,
*MDA↓,
*BACH1↓,
*neuroP↑, Brain-Protective Activity of Hyperoside.
*Stroke↓, Down-regulates TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, TLR4, COX-2, NF-κB, caspase-3, caspase-9, Bax and Bcl-2 expression and prevents CIR injury. Middle cerebral artery occlusion/reperfusion rat model
*ICAM-1↓,
*VCAM-1↓,
*TLR4↓,
*COX2/PTGS2↓,
*RenoP↑, Renal-Protective Activity of Hyperoside.
*NLRP3↓, Suppresses NLRP3, caspase-1 and ASC expression and prevents acute kidney injury induced by lipopolysaccharide. Mouse acute kidney injury model
*Casp1↓,
*ASC↓,
*BioAv↓, low oral bioavailability
*BioAv↑, hyperoside is compatible with other traditional Chinese medicines and they can improve its bioavailability and oral absorption.
*toxicity↓, Firstly, an acute toxicity test of hyperoside showed that its LD50 > 5000 mg/kg
*p‑AMPK↑, In-vitro analyses in astrocytes demonstrated that IBC at 5 and 10 μM concentrations induce AMPK phosphorylation through CAMKK2, promoting autophagy and inhibiting the NLRP3 inflammasome in primary astrocytes
*NLRP3↓,
*NA↝, Two months of treatment of 5x-FAD mice with IBC at 25 and 50 mg/kg significantly improved cognitive functions, as evidenced by enhanced memory and motor performance in behavioral tests.
*cognitive↑,
*memory↑,
*motorD↑,
*Aβ↓, reduce the brain’s amyloid beta levels, resulting in decreased expression of neuroinflammation markers.
*Inflam↓,
*BBB↑, IBC crossed the blood-brain barrier and improved the cognitive deficits in 5x-FAD mice
*BioAv↓, Although ISLT has been globally recognized for its health benefits, its oral administration is still restricted by sparing water solubility, poor bioavailability, and slow dissolution in the intestine.
GlucoseCon↓, ISLT (MGC803 cells: 40 μM, SGC7901 cells: 50 µM) downregulated the expression of glucose transporter four and reduced the uptake of glucose by GC cells.
LDH↓, demonstrated that it suppressed the activity of lactate dehydrogenase and pyruvate dehydrogenase kinase 1 and reduced the production of glycolytic products.
PDK1↓,
Glycolysis↓,
mt-OXPHOS↓, It impaired mitochondrial function while simultaneously suppressing glycolysis and inhibiting mitochondrial oxidative phosphorylation, ultimately leading to energy metabolic collapse in GC cells.
Bax:Bcl2↓, it decreased the Bcl-2/Bax ratio and upregulated cleaved caspase-3/caspase-9 to promote GC cell apoptosis.
cl‑Casp3↑,
cl‑Casp9↑,
Apoptosis↑,
Hif1a↓, hypoxia-inducible factor-1α was downregulated to regulate the energy metabolism and proliferative activity of GC cells
ROS↑, ISLT-17 increases the production of Reactive oxygen species (ROS) in GC cells, thereby inhibiting cell growth.
*AntiDiabetic↑, ISLT possesses therapeutic effects on various diseases such as diabetes, cardiovascular diseases, and kidney diseases by activating the Nrf2 pathway
*cardioP↑,
*RenoP↑, structure in patients with diabetic kidney disease, inhibited oxidative stress and reduced ROS levels, and suppressed the activation of NF-kappa B and NLRP3 inflammasomes and the occurrence of pyroptosis, which played a renal protective role
*ROS↓,
*NF-kB↓,
*NLRP3↓,
*Pyro↓,
*antiPs↑, ISLT (1 mg/kg/day and 2 mg/kg/day) ameliorates psoriasis by inhibiting IL-6 and IL-8 and inhibiting inhibitory nuclear factor-kappa B activity, resulting in a reduction in pro-inflammatory.
*IL6↓,
*IL8↓,
BioAv↑, Compared with traditional oral and injectable methods, transdermal administration possesses significant advantages, such as protection against first-pass effects, improved bioavailability, enhanced patient compliance, prolonged drug stability, and th
BioAv↑, Accordingly, transdermal drug delivery systems containing intercellular lipid components (ceramides) can effectively improve the transdermal efficiency of lipophilic drugs, including ISLT.
BioAv↑, ISLT@NPs possessed significantly higher targeted accumulation in the colon and improved tissue penetration than free DiR, suggesting higher oral bioavailability.
*hepatoP↑, ISL significantly improved the liver pathological changes.
*ROS↓, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes.
*PGC-1α↝,
*NRF2↑,
*HO-1↑,
*NQO1↝,
*Keap1↝,
*GCLC↝,
*GCLM↝,
*NLRP3↓, NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL.
*IL1β↓,
*IL6↓,
*TNF-α↓,
*MIP2↓,
*Bax:Bcl2↓, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3.
*cl‑Casp3↓,
*Inflam↓, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome
*Apoptosis↓,
| - |
in-vitro, |
Nor, |
RAW264.7 |
|
|
|
*TNF-α↓, (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators.
*IL6↓,
*IL1β↓,
*IL18↓,
*PGE2↓,
*NO↓,
*COX2/PTGS2↓, expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced.
*iNOS↓,
*NF-kB↓, inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-κB) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation,
*NLRP3↓,
Showing Research Papers: 1 to 50 of 107
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 107
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
BMP7/OP1↓, 1, CD47↓, 1, miR-124-3p↓, 1, PFS↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 1, Catalase↓, 1, GSH↓, 1, MDA↑, 1, NRF2↓, 1, mt-OXPHOS↓, 1, ROS↑, 5, SOD↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
mtDam↑, 2, PGC-1α↑, 1, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ECAR↓, 1, GlucoseCon↓, 1, Glycolysis↓, 2, HK2↓, 2, LDH↓, 3, LDHA↓, 1, PDK1↓, 2, PKM2↓, 1, SCD1↓, 1, SIRT1↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 2, p‑Akt↓, 1, Apoptosis↑, 9, Bax:Bcl2↓, 1, Bcl-2↓, 1, Casp↑, 1, Casp3↑, 3, cl‑Casp3↑, 1, Casp8↑, 1, Casp9↑, 1, cl‑Casp9↑, 1, Cyt‑c↑, 1, IAP2/BIRC3↓, 1, JNK↓, 1, p27/CDKN1B↑, 1, Pyro↑, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
HCAR2↑, 1, miR-25-5p↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
EZH2↓, 1, other↝, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
ER Stress↑, 1, HSP90↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
TumAuto↑, 4,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↑, 1, P53↑, 3, PARP↑, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK2↓, 1, CDK4↓, 2, cycD1/CCND1↓, 1, cycE/CCNE↓, 1, P21↑, 1, TumCCA↑, 5,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
EMT↓, 2, GSK‐3β↑, 1, HDAC↓, 1, HDAC1↓, 1, NOTCH↓, 1, PI3K↓, 2, STAT3↓, 2, TumCG↓, 3, Wnt↓, 2,
Migration(tgid=13) ⓘ
p‑FAK↓, 1, fascin↓, 1, MALAT1↓, 1, MMP2↓, 1, MMP9↓, 2, Smad1↓, 1, TGF-β↓, 2, TumCI↓, 4, TumCMig↓, 4, TumCP↓, 5, TumMeta↓, 1, TumMeta↑, 1, β-catenin/ZEB1↓, 2,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 3, EGFR↓, 1, EPR↑, 1, Hif1a↓, 2, VEGF↓, 5,
Barriers & Transport(tgid=15) ⓘ
GLUT1↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 1, HCAR2↑, 1, IKKα↓, 1, IL1↓, 1, IL1β↓, 1, IL6↓, 1, Imm↑, 2, Inflam↓, 3, NF-kB↓, 2, NK cell↑, 1, TLR4↓, 1, TNF-α↓, 1,
Protein Aggregation(tgid=19) ⓘ
NLRP3↓, 9, NLRP3↑, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
CDK6↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 1, BioAv↑, 5, BioAv↝, 1, ChemoSen↑, 6, Dose↝, 2, eff↑, 6, RadioS↑, 2, selectivity↑, 2,
Clinical Biomarkers(tgid=22) ⓘ
EGFR↓, 1, EZH2↓, 1, GutMicro↑, 1, IL6↓, 1, LDH↓, 3,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 1, AntiTum↑, 1, chemoP↑, 3, neuroP↑, 1, NP/CIPN↓, 1, QoL↑, 2, radioP↑, 2, toxicity↑, 1, TumVol↓, 2, TumW↓, 1,
Infection & Microbiome(tgid=24) ⓘ
CD8+↑, 2,
Total Targets: 124
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiBio↑, 1, Buty↑, 1, compII↑, 1, diuretic↑, 1, GLP-1R↑, 1, NA↝, 1, SCFAs↑, 1, SpO2↑, 1, Stroke↓, 3,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 24, ARE↑, 1, Bil↑, 2, Catalase↑, 11, Fenton↓, 3, GCLC↑, 2, GCLC↝, 1, GCLM↑, 2, GCLM↝, 1, GPx↑, 5, GPx1↑, 1, GSH↑, 6, GSTA1↑, 1, HNE↓, 1, HO-1↑, 16, Keap1↝, 1, lipid-P↓, 9, MDA↓, 13, MPO↓, 4, NOX4↓, 1, NQO1↑, 3, NQO1↝, 1, NRF2↑, 21, PARK2↑, 1, RNS↓, 1, ROS↓, 33, ROS↑, 1, ROS↝, 1, mt-ROS↓, 1, SIRT3↑, 2, SOD↑, 13, SOD1↑, 1, TAC↑, 1, TBARS↓, 1, uricA↓, 1, VitE↓, 1,
Metal & Cofactor Biology(tgid=2) ⓘ
IronCh↑, 3,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↑, 2, compIII↑, 1, MMP↓, 1, MMP↑, 2, mtDam↓, 2, PGC-1α↝, 1, PINK1↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
12LOX↓, 1, ALAT↓, 5, AMPK↑, 9, p‑AMPK↑, 1, cAMP↑, 1, CREB↑, 2, glucose↓, 1, LDL↓, 4, NADPH↓, 4, PPARγ↓, 1, PPARγ↑, 4, SIRT1↑, 9,
Cell Death(tgid=5) ⓘ
Akt↓, 2, Akt↑, 6, p‑Akt↑, 1, Apoptosis↓, 5, BAX↓, 1, Bax:Bcl2↓, 1, Bcl-2↑, 2, Bcl-xL↑, 1, Casp1↓, 4, Casp12↓, 1, Casp3↓, 2, cl‑Casp3↓, 2, Casp9↓, 1, GranB/GZMB↓, 1, iNOS↓, 6, JNK↓, 3, p‑JNK↓, 1, MAPK?, 1, MAPK↓, 5, p‑MAPK?, 1, p‑MAPK↓, 1, p38↓, 3, p‑p38↓, 1, Pyro↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
Ach↑, 1, cJun↓, 1, other↓, 1, other↑, 1, other↝, 2, TFAM↑, 1, tumCV↓, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↓, 1, p‑eIF2α↓, 1, ER Stress↓, 2, GRP78/BiP↓, 1, XBP-1↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
Beclin-1↓, 1, Beclin-1↑, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, LC3B↑, 1, LC3II↓, 1, p62↓, 1,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↓, 2, cl‑PARP1↓, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
ERK↓, 1, ERK↑, 1, FOXO↑, 1, FOXO3↑, 4, GSK‐3β↓, 5, GSK‐3β↑, 1, mTOR↓, 5, p‑mTOR↓, 1, PI3K↓, 2, PI3K↑, 5, PTEN↓, 1, STAT3↓, 1, STAT3↑, 1,
Migration(tgid=13) ⓘ
5LO↓, 1, AntiAg↑, 2, APP↓, 3, BACH1↓, 1, Ca+2↓, 2, CDK5↓, 1, COL1↓, 1, Fibrosis↓, 1, MMP2↓, 1, MMP3↓, 1, MMP9↓, 1, PKA↑, 1, PKCδ↑, 2, RAGE↓, 1, TGF-β↑, 1, TGF-β1↓, 1, TJ↑, 1, Treg lymp↝, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 1, TXNIP↓, 2, VCAM-1↓, 4, ZO-1↑, 1, α-SMA↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
ATF4↓, 1, Hif1a↓, 1, NO↓, 7, VEGF↓, 2,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 9, BBB↝, 1, IBI↑, 2, OCLN↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
ASC↓, 2, CD25+↑, 1, CD4+↑, 2, COX2/PTGS2↓, 11, FOXP3↑, 1, HMGB1↓, 2, ICAM-1↓, 4, IFN-γ↓, 2, IKKα↓, 1, IL1↓, 1, IL10↑, 4, IL12↓, 1, IL17↓, 2, IL18↓, 2, IL1β↓, 17, IL2↓, 1, IL2↑, 1, IL23↓, 1, IL4↓, 2, IL4↑, 1, IL6↓, 20, IL8↓, 4, Imm↑, 3, Inflam?, 1, Inflam↓, 34, JAK2↓, 1, JAK2↑, 1, LPS↓, 1, M2 MC↑, 1, MCP1/CCL2↓, 4, MIP2↓, 2, MUC2↓, 1, MyD88↓, 1, NF-kB↓, 23, NF-kB↑, 1, p65↓, 1, PGE2↓, 8, RANTES↓, 1, TLR3↓, 1, TLR4↓, 8, TNF-α↓, 20,
Cellular Microenvironment(tgid=17) ⓘ
NOX↓, 1,
Synaptic & Neurotransmission(tgid=18) ⓘ
5HT↑, 2, AChE↓, 4, BChE↓, 1, BDNF↑, 9, BrainVol↑, 1, ChAT↑, 1, GABA↑, 2, MAOA↓, 1, NGF↑, 1, tau↓, 1, p‑tau↓, 3, TrkB↑, 2,
Protein Aggregation(tgid=19) ⓘ
AGEs↓, 1, Aβ↓, 13, BACE/β-secretase↓, 4, NLRP3↓, 42,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
ER(estro)↓, 1, ER(estro)↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 6, BioAv↑, 11, BioAv↝, 3, Dose↓, 1, Dose↑, 1, Dose↝, 6, eff↑, 5, Half-Life↝, 2,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 5, AST↓, 6, Bil↑, 2, BloodF↑, 2, BP↓, 1, BP∅, 1, creat↓, 1, GutMicro↑, 8, IL6↓, 20, MUC19↓, 1, RAGE↓, 1, Urea↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, AntiCan↑, 1, AntiDiabetic↑, 3, antiPs↑, 2, AntiTum↑, 1, cardioP↑, 8, cognitive↑, 11, hepatoP↑, 9, memory↑, 11, motorD↑, 1, neuroP↑, 19, NP/CIPN↓, 1, Obesity↓, 4, OS↑, 2, Pain↓, 1, radioP↑, 1, RenoP↓, 1, RenoP↑, 7, toxicity↓, 4, toxicity↑, 1, toxicity↝, 2, Weight↑, 2,
Infection & Microbiome(tgid=24) ⓘ
AntiFungal↑, 1, AntiViral↑, 2, Bacteria↓, 5, Sepsis↓, 4,
Total Targets: 261
Scientific Paper Hit Count for: NLRP3, NOD-like receptor pyrin domain-containing protein 3
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#:908 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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