BACE Cancer Research Results
BACE, β-site APP-cleaving enzyme: Click to Expand ⟱
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BACE stands for β-site APP-cleaving enzyme, also known as β-secretase. It plays a central role in the pathogenesis of Alzheimer’s disease by initiating the production of amyloid-β (Aβ) peptides, the primary components of amyloid plaques found in the brains of individuals with AD.
-inhibiting BACE1 reduces Aβ production.
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Scientific Papers found: Click to Expand⟱
*antiOx↑, ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain
*Aβ↓,
*ROS↓,
*cognitive↑, Mulberries are a rich source of ANTs that induce antioxidant enzymes and promote cognition
*APP↓, In the cerebral cortex, blackcurrant and bilberry extract reduced APP levels in AD mouse models, but changes in the expression or phosphorylation of tau-protein were not observed
*BBB↑, ANTs cross the blood-brain barrier and protect brain tissue from Abeta toxicity
*Ca+2↓, Aronia melanocarpa. ANTs of this plant decrease intracellular calcium and ROS but increase ATP and mitochondrial potential.
*ATP↑,
*BACE↓, An-NPs also attenuate the protein expression of BACE-1 neuroinflammatory markers, such as phosphonuclear factor kB (p-NF-kB), tumor-necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS),
*p‑NF-kB↓,
*TNF-α↓,
*iNOS↓,
*memory↑, Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice.
*Aβ↓, Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels.
*BACE↓, we observed BACE1 level reduction treated with apigenin.
*antiOx↑, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase.
*BDNF↑, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex.
*p‑CREB↑, After long-term apigenin treatment, coupled with the elevation of BDNF level, enhanced phosphorylated ERK1/2 and CREB expression were detected in the cerebral cortex
*p‑ERK↑,
*ROS↓, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase (SOD) and GSH-Px.
*SOD↑,
*GPx↑,
*neuroP↑, observations are correlated with a prospective neuroprotective, anti-amyloidogenic and neurotrophic effects in AD deficits.
*cognitive↑, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects.
*AChE↓, Recently, Ayaz et al. (2015) reported the AChE, BChE inhibitory and free radicals scavenging efficacy of EOs from the leaves and flowers of Polygonum hydropiper.
*BChE↓,
*ROS↓,
*other↓, , Ahmad et al. (2016) reported the anti-cholinesterase and antiradicals potentials of EO from Rumex hastatus D. Don. GC-MS analysis of EO revealed the presence of 123 compounds. I
*other↓, (Ahmad et al., 2016). Okello et al. (2008) reported the in vitro AChE, BChE inhibitory activity of flower oil from Narcissus poeticus L. belonging to family Amaryllidaceae.
*other↓, The EO from Marlierea racemosa Vell. (Myrtaceae) were evaluated by Souza et al. (2009) against AChE enzyme.
*other↓, C. salvifolius exhibited AChE inhibitory activity with IC50 value of 58.1 μg/ml. Whereas, C. libanotis, C. creticus and C. salvifolius showed significant inhibitory activities against BChE with IC50 values of 23.7, 29.1 and 34.2 μg/ml respectively.
*other↓, Rosemary EO also possess moderate AChE inhibitory activity and can synergistically act with 2-pinene and 1,8-cineole.
*memory↑, Owing to the memory enhancing capabilities of Salvia lavandulifolia Vahl (Spanish sage),
*BACE↓, EOs can inhibit the activity of BACE1 to hamper the Aβ load.
*Mood↑, Lavandula angustifolia Mill. and Melissa officinalis L. belonging to Lamiaceae for the management of agitation in individuals with severe dementia. The sedative and calming effect of both EOs is already established which can contribute in consolidati
*motorD↑, lavender EO: locomotor activity and motor functions were improved in animal models.
*OS↑, The untreated Act5C-Aβ42 flies live for approximately 16 days, while the Act5C-Aβ42
treated with Ashwagandha showed improvement in their lifespan living up to 29 days
*BACE↓, shwagandha was also shown to down-regulate beta-secretase 1
(BACE1) a
*neuroP↑, fucoxanthin and astaxanthin, natural carotenoids abundant in algae, has shown to possess neuroprotective properties through antioxidant, and anti-inflammatory characteristics in modulating the symptoms of AD.
*antiOx↑,
*Inflam↑,
*AChE↓, Fucoxanthin and astaxanthin exhibit anti-AD activities by inhibition of AChE, BuChE, BACE-1, and MAO, suppression of Aβ accumulation.
*BACE↓,
*MAOA↓,
*Aβ↓,
*memory↑, Recently, Che, Li (Che et al., 2018) reported that astaxanthin possessed memory enhancement.
*MDA↓, Astaxanthin, as an antioxidant, helps to reduce oxidative stress by lowering malondialdehyde (MDA) levels and increasing SOD activity by activation of the NrF2/HO-1 pathway
*SOD↑,
*NRF2↑,
*HO-1↑,
*NF-kB↓, astaxanthin showed NFκB inhibitory activity which caused the downregulation of BACE-1 expression, resulting in Aβ reduction
*GSK‐3β↓, astaxanthin dose-dependently attenuated the GSK-3β activity
*ChAT↑, astaxanthin could reduce neuroinflammation via reducing iNOS expression and spine loss on the hippocampal CA1 pyramidal neurons, and restoring the ChAT expression in the medial septal nucleus
*iNOS↓,
*ROS↓, astaxanthin treatment decreased the ROS production and enhanced the cell growth.
*BBB↑, Astaxanthin can attenuate neurological dysfunction because of its unique chemical structure and can cross the BBB to enter the brain tissue
*AChE↓, Berberine (9) has gained considerable attention due to its wide pharmacological potentials and several biological properties, such as acetylcholinesterase and butyrylcholinesterase inhibitory, antioxidant, monoamine oxidase oxidase,
*Aβ↓, amyloid-b peptide level-reducing, cholesterol- lowering and renoprotective activities
*LDL↓,
*RenoP↑,
*BChE↓,
*eff↑, Above all, the berberine-pyrocatechol hybrid (14) showed a strong AChE inhibitor activity (IC50 of 123 ± 3 nM)
[34]
*BACE↓, Curcumin: inhibite the rBACE1 activity [42]. In addition, it has made good inhibitory effect on acetylcholinesterase activity
*AChE↓, EGCG promoted brain health, prevented AD progression, and inhibited the AChE activity [52,53].
*eff↑, EGCG could enhance the effect of huperzine A on inhibiting AChE.
*Inflam↓, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.
*antiOx↓,
*AChE↓,
*BChE↓, berberine exerts inhibitory effects on the four key enzymes in the pathogenesis of AD: acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A, and monoamine oxidase B
*MAOA↓,
*MAOB↓,
*lipid-P↓, Fig3
*GSH↑,
*ROS↓,
*APP↓,
*BACE↓,
*p‑tau↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*MAPK↓,
*PI3K↓,
*Akt↓,
*neuroP↑, neuroprotective effects of berberine have been extensively studied
*memory↑, berberine displayed significant effects in preventing memory impairment in these mechanistically different animal models, suggesting an over-all improvement of memory function by berberine
*APP↓, Berberine can regulate APP expression and improve cognitive function in animal models of AD,
*cognitive↑,
*Aβ↓, Berberine is involved in regulating APP modification, which may inhibit Aβ production through BACE1 inhibition and regulation of γ-secretase substrates.
*BACE↓,
*tau?, berberine may be a good multi-targeted drug that can modulate AD related substances tau, PP-2A, Aβ, APP, or BACE-2.
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*BioAv↓, Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption
*Inflam↓, various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects.
AntiCan↑,
*neuroP↑, many studies have focused on the effect of BCA on neurodegenerative diseases, especially PD and AD
chemoPv↑, BCA Has Chemopreventive Activity Against Various Cancers
Dose↝, BCA is metabolized in the gut to GEN or formononetin, which is converted to daidzein and then to equol (Knight and Eden, 1996).
*SOD↑, BCA also has a gastroprotective effect through the enhancement of cellular metabolic cycles, as evidenced by increases in superoxide dismutase (SOD) and nitric oxide (NO) activity, decreases in the malondialdehyde (MDA) and Bax levels, and increases
*MDA↓,
*BAX↓,
*HSP70/HSPA5↑, and increases in Hsp70 expression
*AntiDiabetic↑, BCA is well known for its antidiabetic and hypolipidemic effects.
*Insulin↑, BCA increases the circulating insulin levels and improves insulin sensitivity, leading to body weight control, an increase in liver glycogen, and a decrease in plasma glucose
*TNF-α↓, BCA inhibits the production of inflammatory mediators, such as TNF-α, interleukin-1β (IL-1β), IL-6, iNOS, COX-2, MMP-9, and NO, in various inflammatory responses
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2↓,
*MMP9↓,
*ROS↓, BCA scavenges ROS and increases SOD activity
*PGE2↓, BCA significantly reduces the synthesis of prostaglandin E2 and/or thromboxane B2 by inhibiting COX-2 expression
*BACE↓, BCA effectively inhibits the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
*BioAv↑, Various attempts have been made to improve the solubility and bioavailability of BCA, including the use of liposomes
P-gp⇅, Interestingly, BCA has been found to stimulate P-gp in some studies (An and Morris, 2010). Therefore, the effect of BCA on P-gp may be substrate dependent.
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*AntiDiabetic↑, Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action.
*neuroP↑, Biochanin-A has been shown to have a potential neuroprotective impact by modulating multiple critical neurological pathways.
*toxicity↓, Unlike chemical agents such as chemotherapeutic agents, isoflavones have shown zero toxicity to humans
*CYP19↓, Biochanin-A inhibits CYP19 and negatively affects the synthesis of oestrogen in the body which enhances the anti-oestrogenic property in hormone-influenced cancer such as prostate cancer and breast cancer
p‑Akt↓, Biochanin-A inhibits Akt phosphorylation thereby downregulates mTOR signals and disrupts the cell cycle.
mTOR↓,
TumCCA↑,
P21↑, Biochanin-A cause apoptosis in lung cancer by increasing p21, caspase-3, and Bcl-2 levels. It lowers E-cadherin and blocks metastasis.
Casp3↑,
Bcl-2↑,
Apoptosis↑,
E-cadherin↓,
TumMeta↓,
eff↑, The synergism of biochanin-A with 5-fluorouracil evidenced in Caco-2 and HCT-116 cell lines indicates the modulatory influence of biochanin-A in colon cancer treatment.
GSK‐3β↓, It blocked the “Akt and GSK3β phosphorylation and boosted the degradation of β-catenin” ( Mahmoud et al., 2017).
β-catenin/ZEB1↓,
RadioS↑, Biochanin-A when combined with gamma radiation on HT29 cells, which is resistant to radiation, had revealed a reduction in cell proliferation.
ROS↑, Raised levels of ROS, lipid peroxidation, MMP, caspase-3 have been observed more in the treatment group with significant apoptosis
Casp1↑,
MMP2↓, biochanin-A influenced the tumour invasion capacity by lowering matrix-degrading enzymes (MMP 2 and MMP 9) tested in U87MG cells
MMP9↓,
EGFR↓, Biochanin-A by lowering EGFR, p-ERK (Extracellular signal related kinases), p-AKT (Protein kinase-B), c-myc, and MT-MMP1 (Membrane type matrix metalloproteinase) activation, inhibited cell survival.
ChemoSen↑, Biochanin-A synergistically improved temozolomide anti-cancer ability in GBM
PI3K↓, Cell signalling pathways MAP kinase, PI3 kinase, mTOR, matrix metalloproteases, hypoxia-inducible factor, and VEGF were inhibited by biochanin-A, making it suitable in treating GBM
MMPs↓,
Hif1a↓,
VEGF↓,
*ROS↓, anti-diabetic mechanism of biochanin-A is by decreasing oxidative stress
*Obesity↓, strongly suggest that biochanin-A has therapeutic potential in the treatment of obesity and the prevention of cardiovascular disease
*cardioP↑,
*NRF2↑, Biochanin-A up-regulated the Nrf-2 pathway while suppressing the NF-κB cascade,
*NF-kB↓, By activating the Nrf-2 pathway and inhibiting NF-κB activation, biochanin-A may reduce obesity and its related cardiomyopathy by decreasing oxidative stress and inflammation
*Inflam↓,
*lipid-P↓, cardio-protective effects by controlling lipid peroxidation
*hepatoP↑, biochanin-A influence the elevated hepatic enzyme level, such as AST, ALP, ALT, bilirubin, etc., and found to be a promising molecule in hepatotoxicity models
*AST↓,
*ALP↓,
*Bacteria↓, The results indicate that biochanin-A may be an effective alternate to antibiotics for alleviating SARA in cattles
*neuroP↑, the neuroprotective effects of biochanin-A might be attributed to the activation of the Nrf2 pathway and suppression of the NF-κB pathway
*SOD↑, Biochanin-A reduced oxidative stress in the brain by augmenting SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) and repressing MDA (malondialdehyde) levels.
*GPx↑,
*AChE↓, Acetylcholinesterase activity was found decreased in a dose-reliant manner amongst biochanin-A treated animals
*BACE↓, Biochanin-A non-competitively inhibited BACE1 with an IC 50 value of 28 μM.
*memory↑, estore learning and memory deficits in ovariectomized (OVX) rats.
*BioAv↓, The bioavailability of biochanin-A is poor.
*cognitive↑, Vitamin A deficiency (VAD) has been shown to affect cognitive functions. VA supplementation improves cognitive deficits.
*BACE↓, We found that MVAD, mostly prenatal MVAD, promotes beta-site APP cleaving enzyme 1 (BACE1)-mediated Aβ production and neuritic plaque formation, and significantly exacerbates memory deficits in AD model mice
*memory↑, Supplementing a therapeutic dose of VA rescued the MVAD-induced memory deficits.
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TumCG↓, In vitro experiments further revealed that BJOEI could suppress cell growth and invasion, arrest cells at the S stage, and cause cell apoptosis
TumCI↓,
TumCCA↑, BJOEI induced cell cycle arrest and cell apoptosis
Apoptosis↑,
BAX↑, BJOEI upregulated BAX and cleaved caspase3 expression and downregulated BCL2 expression
cl‑Casp3↑,
Bcl-2↓,
MMP2↓, expression of MMP2, PTGS2, BACE1, and TOP2A were downregulated.
BACE↓,
TOP2↓,
*cognitive↑, BM supplementation was able to improve cognitive functions, suppress Aβ formation by reducing BACE-1 activity
*Aβ↓,
*BACE↓,
*Inflam↓, Inflammatory and oxidative stress markers were attenuated in the brain regions of BM supplemented animals.
*ROS↓,
*antiOx↑, anti-inflammatory and anti-oxidant action
*ZO-1↓, Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression
*cl‑Casp3↓, Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio
*Bax:Bcl2↓,
*MDA↓, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice
*Apoptosis↓,
*Aβ↓,
*BACE↓,
*cognitive↑,
*BioAv↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
memory↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
P-gp↓, This may be caused by a higher dose of BO inhibiting the action of the P-gp transporter in intestinal mucosa and CYP450 metabolism in the liver.
BioEnh↑,
*memory↑, pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress.
*Inflam↓,
*ROS↓,
*ER Stress↓, celastrol suppressed AD progression by targeting ER stress
*neuroP↑, celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.
*Dose↝, administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. (1, 3, 6 mg/kg/day) for 2 days
*MDA↓, AD mouse group treated with celastrol showed lower levels of protein carbonyl and MDA and higher activity of CAT and SOD compared to the AD group
*SOD↑,
*Catalase↑,
*Aβ↓, Research has shown that celastrol can reduce cell death and Aβ production in cell experiments
BACE↓, celastrol treatment significantly restored the expression of BACE1, LRP1, NEP, and RAGE in the brain
LRP1↑, Activation of LRP1 by celastrol may lead to the attenuation of AD symptoms.
RAGE↓,
*Aβ↓, Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression
*BACE↓,
*memory↑, Curcumin Ameliorates Memory Decline
*antiOx↑, Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties
*Inflam↓,
*AntiAge↑, Its potential anti-aging properties are due to its power to alter the levels of proteins associated with senescence, such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and sirtuins
*AMPK↑,
*SIRT1↑,
*NF-kB↓, preventing pro-aging proteins, such as nuclear factor-kappa-B (NF-κB) and mammalian target of rapamycin (mTOR)
*mTOR↓,
*NLRP3↓, Moreover, curcumin, by inhibiting the NF-κB pathway, can directly restrain the assembly or even inhibit the activation of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome
*NADPH↓, by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and elevating the activity of antioxidant enzymes and consequently lowering reactive oxygen species (ROS)
*ROS↓,
*COX2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1↓,
*IL1β↓, by decreasing IL-1β, IL-17, IL-23, TNF-α, and myeloperoxidase, enhancing levels of IL-10, and downregulating activation of NF-κB
*IL17↓,
*IL23↓,
*TNF-α↓,
*MPO↓,
*IL10↑,
*lipid-P↓, curcumin showed a significant decline in lipid peroxidation and increased superoxide dismutase levels, in addition to a reduction in Aβ aggregation and tau hyperphosphorylation through the regulation of GSK3β, Cdk5, p35, and p25
*SOD↑,
*Aβ↓,
*p‑tau↓,
*GSK‐3β↓,
*CDK5↓,
*TXNIP↓, Curcumin also has an inhibitory role on the thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway
*NRF2↑, well as upregulation of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), HO-1, and γ-glutamyl cysteine synthetase (γ-GCS) in brain cells.
*NQO1↑,
*HO-1↑,
*OS↑, significant improvement in OS, and a positive evolution in memory and spatial learning
*memory↑,
*BDNF↑, Besides that, it promoted neurogenesis through increasing brain-derived neurotrophic factor (BDNF) levels
*neuroP↑, Curcumin can promote neuroprotection
*BACE↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.
*AChE↓, Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM : All five compounds weakly inhibited BChE and BACE-1.
*BACE↓,
*MAOB↓, inhibited MAO-B by more than 50%.
*p‑tau↓, EGCG decreased the hyperphosphorylation of Tau in hippocampus
*BACE↓, BACE1 expression and activity as well as the expression of Aβ1-42 were suppressed by EGCG.
*Aβ↓,
*Ach↑, Moreover, EGCG promoted Ach content by diminishing the activity of AchE.
*AChE↓,
*antiOx↑, to improve the antioxidant system and learning and memory function of rats with AD.
*memory↑,
*hepatoP↑, notable components found in coffee have been shown to exert anti-diabetic and hepatoprotective functions
*ROS↓, EGCG Improved the Antioxidant System and Scavenged Free Radicals in AD Rats
*GPx↑, Compared with the AD rats, GPx and T-SOD activities were enhanced in the AD rats with EGCG treatment, especially in the AD rats treated with 250 mg/kg EGCG.
*SOD↑,
*neuroP↑, brain protection properties
*Aβ↓, Emodin suppresses Aβ deposition and tau phosphorylation.
*p‑tau↓,
*BACE↓, emodin downregulates the activity of β-site APP-cleaving enzyme 1 (BACE1) and increases protein phosphatase 2A levels
*cognitive↑, Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA
*ERK↓, a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels
*p‑Akt↓,
*AChE↓, brain levels of AChE and BACE were substantially reduced in BPA + FA rats.
*BACE↓,
*neuroP↑, neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.
*ROS↓, FA was sufficient to trigger antioxidant capabilities and decrease intracellular reactive oxygen species (ROS
*MDA↓, BPA + FA revealed a substantial reduction in MDA levels compared to rats intoxicated with BPA
*GSH↑, BPA + FA revealed a significant increment of GSH associated with a significant decrease in GSSG
*GSSG↓,
*p‑tau↓, BPA + FA showed a significant decline in the brain level of pTau compared to intoxicated rats.
*lipid-P↓, inhibit lipid peroxidation
*Aβ↓, FA has significantly counteracted the deleterious effect of BPA by decreasing Aβ 1–42, as previously reported
*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,
*neuroP↑, has neuroprotective effects against a series of pathological cascades in AD, including beta-amyloid formation, neuroinflammation, oxidative stress, and mitochondrial dysfunction.
*Inflam↓,
*ROS↓,
*BACE↓, Ginsenoside Re inhibits the activity of BACE1 by increasing PPARγ expression at the mRNA and protein levels in N2a/APP695 cells and thereby reduces the generation of Aβ1–40 and Aβ1–42
*PPARγ↑,
*Aβ↓, ginsenosides Rb1, Rd, Re, and Rg1 can inhibit Aβ aggregation to regulate the phosphorylation of tau protein in the prevention and treatment of AD.
*p‑tau↓, inhibiting tau phosphorylation
*NF-kB↓, Rd pretreatment at 10 mg/kg significantly suppresses the NF-κB pathway activity, reducing the generation of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)
*IL1β↓,
*IL6↓,
*TNF-α↓,
*ROS↓, Ginsenoside Rg1 can reduce the NADPH oxidase 2 (NOX2)–mediated ROS production and neuronal apoptosis
*CREB↓, Ginsenoside F1 can decrease phosphorylated cAMP-response element binding protein (CREB) and increase cortical BDNF levels in the hippocampus, reducing Aβ plaques and improving memory function of APP/PS1 double-transgenic AD mice
*BDNF↑,
*memory↑,
*ROS↓, Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment.
*NO↓,
*BACE↓, BACE-1), amyloid beta (Aβ), r (BDNF), (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases.
*BDNF↑, see figure 5
*VEGF↑,
*p‑tau↓, t-tau and p-tau levels reduced dramatically in different ages within 4 weeks of treatment;
*MCP1↓, MCP-1 (p < 0.001) (Figure 7A), IL-6 (p < 0.05) (Figure 7B), and VEGF-A (Figure 7C) levels significantly decreased
*IL6↓,
*cognitive↑, H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction
*toxicity∅, H2 gas inhalation treatment did not cause any adverse effects, indicating that it was safe.
*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↓,
*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.
*AChE↓, effects of this alkaloid have been attributed to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), acting as an acetylcholinesterase inhibitor (AChEI).
*neuroP↑, summarize the neuroprotective effects of HupA on AD,
*BBB↑, HupA is an unsaturated sesquiterpene alkaloid compound that effectively crosses the blood-brain barrier (BBB), acting as a mixed-competitive, reversible, and selective AChE inhibitor
*Half-Life↑, with a half-life of 5 h in the bloodstream, reaching a peak concentration at approximately 60 min in humans
*cognitive↑, hows evidence of improved cognition
*Dose↝, significant cognitive enhancement in patients receiving 0.4 mg of HupA twice a day.
*BACE↓, while downregulating the membrane translocation of BACE1
*IronCh↑, HupA might act directly as an Fe2+ chelator, reducing the capacity of IRP-1 to induce APP translation
*TfR1/CD71↓, HupA also downregulates TFR1 expression in mice in vivo, which reduces the uptake of transferrin-bound iron (TBI) in neurons
*ROS↓, HupA indirectly reduces ROS
*memory↑, Hup A (0.1, mg · kg−1 · d−1) improved both the abilities of object recognition and spatial memory in HFD-fed mice, but not in ob/ob mice.
*p‑Akt↑, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but not ob/ob mice.
*BACE↓, In addition, Hup A (0.3, mg · kg−1 · d−1) significantly decreased cortical β-secretase (BACE1) expression.
*cognitive↑, Hup A (0.1, mg · kg−1 · d−1) can effectively improve the cognitive functions, at least in diet-induced obese mice.
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*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats
*ROS↓, Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins.
*PI3K↑,
*Akt↑,
*NRF2↓,
*antiOx↑,
*BACE↓, lycopene inhibited β -secretase (BACE) activity in M146L cells.
*MDA↓,
*cognitive↑, EMFs could protect from the cognitive impairment or improve the memory in mice [9
*memory↑,
*BACE↓, figure 2
*antiOx↑, Moringa oleifera (MO), a naturally occurring plant with high antioxidative, anti-inflammatory, and neuroprotective effects,
*Inflam↓,
*neuroP↑,
*Aβ↓, decreased Aβ production through downregulation of BACE1.
*BACE↓, protein level of BACE1 was also increased in the Hcy group compared with control, and MO treatment significantly reduced it to control level except for the preventive low dose of MO
*cal2↓, HHcy rats were accompanied by a decrease in calpain activity under MO treatment
*p‑tau↓, MO alleviates tau hyperphosphorylation and Aβ pathology i
*ROS↓, HHcy has been reported to induce increase oxidative stress [15] while MO reduced it
*SOD↑, However, treatment with MO significantly prevented and rescued the Hcy induced decrease in SOD activity in both serum (Fig. 1A) and hippocampal lysate
*MDA↓, MO treatment decreased the level of serum (Fig. 1C) and hippocampal (Fig. 1D) MDA elevated by the Hcy injection in the rats.
*cognitive↑, MO attenuated the cognitive impairments induced by homocysteine
*memory↑, These results indicate that MO treatment significantly prevented and improved Hcy induced learning and memory deficits.
*antiOx↑, multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues.
*Inflam↓,
*AChE↓,
*neuroP↑,
*Mood↑, MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments.
*cognitive↑,
*memory↑,
*Aβ↓, MO treatment abrogated the Aβ burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels.
*BACE↓,
*AEP↓,
*IDE↑,
*NEP↑,
*LRP1↑,
*PSD95↑, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice
*STEP↓, These results suggest that MO modulates the PP2B/DARPP-32/PP1 axis to downregulate STEP activity thereby improving GluN2B Tyr1472 phosphorylation in APP/PS1 mice.
*APP↓, data suggest that MO downregulates the amyloidogenic processing of APP as well as improves Aβ clearance to decrease the Aβ burden in these mice.
*cognitive↑, Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD
*Apoptosis↓, HE can modulate neural activity, such as increasing synaptic plasticity, reducing apoptosis, decreasing Aβ plaques, and inhibiting acetylcholinesterase (AChE) and BACE1
*Aβ↓,
*AChE↓,
*BACE↓,
*BACE↓, significant reduction in the paired helical filament (PHF), β-amyloid (βA) 1–40 and βA 1–42 levels and a decrease in BACE1-mediated cleavage of APP (into CTFβ).
*cognitive↑, protects cognitive and emotional function in aged 3xTg-AD mice.
*ROS↓, These potential uses may be due to its high oxygen radical scavenging activity or its ability to inhibit xanthine oxidase and lipid peroxidation in vitro
*lipid-P↓,
*iNOS↓, inhibiting iNOS (Martinez-Florez et al., 2005) and regulating the expression of COX-2
*COX2↓,
*BBB↑, ability to penetrate the blood brain barrier
*neuroP↑, n addition to neuroprotection, quercetin has been suggested to exert other beneficial effects on the central nervous system (CNS), such as anti-anxiety and cognitive enhancement, by stimulating or inhibiting enzyme activities/signal transduction path
*other↓, remarkable reduction in the βA 1–40 and βA 1–42 levels in the hippocampus of the quercetin-treated 3xTg-AD mice compared to the vehicle-treated 3xTg-AD mice
*memory↑, Quercetin improves the spatial learning and memory task performance of 3xTg-AD mice
*cognitive↑, early-middle stage of AD pathological development period ameliorates cognitive dysfunction and the protection effect was mainly related to increased Aβ clearance and reduced astrogliosis.
*Aβ↓, Quercetin enrich diet prevented cognitive dysfunction through increasing Aβ clearance and astrocyte function. has been demonstrated that it could inhibit the aggregation of Aβ
*neuroP↑, quercetin may have neuro-protective effects and slow down the progression of degenerative diseases
*BACE↓, The results showed that the protein level of CTFβ and BACE1 was decreased
*p‑SMAD2↓, protein level of p-Smad2 and p-STAT3 were decreased in quercetin enrich diet
*p‑STAT3↓,
*SPARC↓, quercetin enrich diet (1 month-9 months) significantly reduced the mRNA and protein level of Hevin and SPARC compared with normal diet.
*neuroP↑, state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented
*Inflam↓, Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol contained in red wine, peanuts, and some berries, is known for its anti-atherosclerotic, anti-inflammatory, antioxidant, and longevity-promoting properties
*antiOx↑,
*GSH↑, ↑glutathione in brain
*HO-1↑, ↑HO-1 ↓iNOS in hippocampus
*iNOS↓,
*BDNF↑, ↑BDNF, ↑pCREB, ↑PKA, ↑BCl-2 expression, ↓BAX expression, ↓IL-1β, IL-6, in hippocampus
*p‑CREB↑,
*PKA↑,
*Bcl-2↑,
*BAX↓,
*IL1β↓,
*IL6↓,
*MMP9↓, ↓MMP-9 in cerebrospinal fluid
*memory↑, ↑memory performance
*AMPK↑, ↑AMPK, ↑PGC-1, ↓NF-κB / IL-1β / NLRP3 in hippocampus and prefrontal cortex
*PGC-1α↓,
*NF-kB↓,
*Aβ↓, may counteract the formation of neurotoxic Aβ
*SIRT1↑, Resveratrol via SIRT-1 can, therefore, be expected to reduce the level of hyperphosphorylated tau and provide protection against neurodegeneration.
*p‑tau↓,
*PP2A↑, resveratrol by lowering the expression of MID1 ubiquitin ligase increases protein phosphatase 2A (PP2A) activity and promotes tau dephosphorylation by preventing its accumulation
*lipid-P↓, resveratrol abolishes Aβ-induced lipid peroxidation and expression of heme oxygenase-1 (HO-1) reduction;
*NLRP3↓, Researchers achieved a significant reduction in the levels of NF-κB (nuclear factor κ-light-chain enhancer of activated B cell), interleukin 1β and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammation markers
*BACE↓, figure 1
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*p‑tau↓, Resveratrol induces dephosphorylation of Tau
*PP2A↑, resveratrol, a polyphenol, significantly induces PP2A activity and reduces Tau phosphorylation at PP2A-dependent epitopes.
*neuroP↑, resveratrol is more and more being established as a neuroprotective drug after ischemic brain injury and in neurodegenerative disorders including Parkinson’s Disease13,14, AD15,16 and Huntington’s Disease
*antiOx↑, resveratrol has anti-oxidant activity19,20, inhibits cycloxygenase activity21,22, ribonucleotide reductase23, protein kinase C24, DNA polymerase 25 and has antiestrogenic properties26,27 and anti-platelet activity
COX2↓,
*AntiAg↑,
*SIRT1↑, it activates Sirt1, an NAD+-dependent protein deacetylase28,29 and also has been demonstrated to activate AMP kinase (AMPK)30,31, an important glucose sensor that inhibits acetyl-CoA carboxylase, thereby increasing oxidation of fatty acids and decre
*AMPK↑,
*Acetyl-CoA↓,
*FAO↑,
*ADAM10↑, Resveratrol has been suggested to induce the α-secretase ADAM10, which outcompetes BACE1 and thereby reduces Aβ-production
*BACE↓,
*Aβ↓,
*memory↑, interestingly, the resveratrol-mediated reduction of Aβ increases life span and improves learning and memory
*Inflam↓, reduces neuroinflammation47 and reduces oxidative stress48.
*ROS↓,
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*antiOx↑, SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties,
*Inflam↓,
*Half-Life↝, SFN in rats reaches the plasma peak in 4 h, with an average half-life of about 2.2 h
*NRF2↑, Nrf2 expression can be regulated by SFN,
*NQO1↑, oxidoreductase 1 (NQO-1), heme oxygenase 1 (HO-1), GSH S-transferase, and thioredoxin reductase, thus counteract the oxidative stress
*HO-1↑, intracellular increase of GSH, as well as HO-1 and NQO-1 activity
*TrxR↑,
*ROS↓,
*TNF-α↓, regulating the levels of inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL) 6, IL-1β, inducible nitric oxide synthetase (iNOS), and cyclooxygenase-2 (COX-2)
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2↓,
*Aβ↓, SFN inhibited Aβ aggregation, tau hyperphosphorylation, as well as oxidative stress, evaluated through GSH and malondialdehyde (MDA) levels
*GSH↑, reduction of levels of MDA, TNF-α, and IL-1β, as well as by the increase of GSH
*cognitive↑, SFN treatment improved cognitive and locomotor deficits evaluated by Morris water maze and open field test.
*BACE↓, SFN, according to a dose-dependent mechanism, can inhibit BACE-1 and consequently Aβ aggregation
*HSP70/HSPA5↑, SFN increased the levels of co-chaperone of heat shock protein (HSP), C-terminus of HSP 70-interacting protein (CHIP)
*neuroP↑, SFN, through mechanisms that involve Nrf2 activation, can play a protective effect for counteracting the neurodegeneration that occurs in the PD
*ROS↓, SFN treatment has avoided both ROS production and membrane damage.
*BBB↑, SFN protected the integrity of BBB, as shown by tight junction proteins occludin and claudin-5 levels, as well as by the reduction in the expression levels of matrix metallopeptidase 9,
*MMP9↓,
*NRF2↑, Sulforaphane potently induces transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated expression of detoxification, anti-oxidation
*antiOx↑,
*neuroP↑, The study on the neuroprotective effects of sulforaphane began in 2004 with studies showing the protective effects on neurons
*Aβ↓, every other day 10 mg/kg i.p. for 2 months in cortex: (1) reduced the numbers of Aβ plaques/mm2
in cerebral cortex
*BACE↓, reduced BACE1 protein expression
*NQO1↑, increased NQO1 transcript and protein expression
*IL1β↓, decreased IL-1β and TNF-α
*TNF-α↓,
*IL6↓, (1) decreased IL-1β and IL-6 (2) decreased COX-2 and iNOS (3) reduced NF-κB p-p65
*COX2↓,
*iNOS↓,
*NF-kB↓,
*NLRP3↓, reduced NLRP3 inflammasome
*Ca+2↓, decreased intracellular Ca2+ levels
*GSH↑, in brain: (1) increased GSH (2) decreased MDA
*MDA↓,
*ROS↓, (1) decreased ROS and MDA, (2) increased SOD activity
*SOD↑,
*HO-1↑, increased NQO1, HO-1
*TrxR↑, increased HO-1 and TrxR expression
*cognitive↑, ameliorated cognitive deficits
*tau↓, figure 1
*HSP70/HSPA5↑,
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*BioAv↓, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone.
*BioAv↑, TQ nanoparticle formulation shows better bioavailability than free TQ,
*Inflam↓, anti-inflammatory effects of TQ involve multiple complex signaling pathways as well as molecular mechanisms
*antiOx↑, antioxidant activity from the inhibition of oxidative stress
*ROS↓,
*GSH↑, GSH prevented ROS-mediated oxidative stress damage
*GSTs↑, TQ was found to exhibit antioxidant properties by increasing the levels of GSH and glutathione-S-transferase enzyme alpha-3 (GSTA3)
*MPO↓, TQ significantly reduced the disease activity index (DAI) and myeloperoxidase (MPO) activity, protecting the internal microenvironment of the colon.
*NF-kB↓, TQ reduced NF-κB signaling gene expression while alleviating the increase of COX-2 in skin cells induced by 12-O-tetradecanoylphorbol-13-acetate
*COX2↓,
*IL1β↓, reduced the expression of inflammatory factors such as IL-1β, TNF-α, IFN-γ, and IL-6
*TNF-α↓,
*IFN-γ↓,
*IL6↓,
*cardioP↑, TQ may exhibit substantial effects in the control of inflammation in CVD
*lipid-P↓, TQ reduces lipid accumulation and enhances antioxidant capacity and renal function.
*TAC↑,
*RenoP↑,
Apoptosis↑, Breast cancer TQ induces apoptosis and cell cycle arrest; reduces cancer cell proliferation, colony formation, and migration;
TumCCA↑,
TumCP↓,
TumCMig↓,
angioG↓, Colorectal Cancer (CRC) TQ inhibits the angiogenesis
TNF-α↓, Lung cancer TQ inhibits tumor cell proliferation by causing lung cancer cell apoptosis to significantly arrest the S phase cell cycle and significantly reduce the activity of TNF-a and NF-κB
NF-kB↓,
ROS↑, Pancreatic cancer TQ significantly increases the level of ROS production in human pancreatic cancer cells
EMT↓, TQ initiates the miR-877-5p and PD-L1 signaling pathways, inhibiting the migration and EMT of bladder cancer cells.
*Aβ↓, TQ significantly reduced the expression of Aβ, phosphorylated-tau, and BACE-1 proteins.
*p‑tau↓,
*BACE↓,
*TLR2↓, Parkinson’s disease (PD) TQ inhibits activation of the NF-κB pathway.
TQ reduces the expression of TLR-2, TLR-4, MyD88, TNF-α, IL-1β, IFN-β, IRF-3, and NF-κB.
*TLR4↓,
*MyD88↓,
*IRF3↓,
*eff↑, TQ pretreatment produced a dose-dependent reduction in the MI area and significantly reduced the elevation of serum cardiac markers caused by ISO.
eff↑, Curcumin and TQ induced apoptosis and cell cycle arrest and reduced cancer cell proliferation, colony formation, and migration in breast cancer cells
DNAdam↑, nanomedicine with TQ that induced DNA damage and apoptosis, inhibited cell proliferation, and prevented cell cycle progression
*iNOS↓, TQ significantly reduced the expression of COX-2 and inducible nitric oxide synthase (iNOS)
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*antiOx↑, urolithin A has received an increasing amount of attention as a novel candidate with anti-oxidative and neuroprotective effects in AD
*neuroP↑,
*Ca+2↓, We found that urolithin A-lowered mitochondrial calcium influx significantly alleviated high glucose-induced mtROS accumulation
*Aβ↓, and expression of amyloid beta (Aβ)-producing enzymes, such as amyloid precursor protein (APP) and β-secretase-1 (BACE1), as well as Aβ production.
*BACE↓,
*p‑tau↓, Urolithin A injections in a streptozotocin (STZ)-induced diabetic mouse model alleviated APP and BACE1 expressions, Tau phosphorylation, Aβ deposition, and cognitive impairment.
*cognitive↑,
*neuroP↑, urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy.
*Half-Life↝, Urolithins appear in the human circulation within a few hours of consumption of ET-containing foods, reaching maximum concentrations after 24–48 h and complete excretion in urine/faeces within 72 h.
*BBB↑, urolithins can permeate the blood–brain barrier (BBB)
*toxicity↓, Urolithins are relatively non-toxic, as shown by studies in rats. The lethal dose 50 (LD50) has been found to be greater than 5 g/kg body weight in rat
*Inflam↓, In a study of Fisher rats [185], urolithin A was found to be the most effective anti-inflammatory compound derived from pomegranate consumption.
*Strength↑, Another clinical trial has shown that UA at doses of 500 mg and 1,000 mg for 4 weeks modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elders [
*BACE↓, There is evidence suggesting that these molecules inhibit BACE1 activity, leading to reduced Aβ production.
*Aβ↓,
*MitoP↑, Urolithin A May Trigger Mitophagy
*SIRT1↑, Activation of SIRT1/3, AMPK, PGC1-α and Inhibition of mTOR1
*SIRT3↑,
*AMPK↑,
*PGC-1α↑,
*mTOR↓,
*PARK2↑, urolithin A (1000 mg) has been shown to transcriptionally increase Parkin and BECN1 levels after 28 days of treatment in humans
*Beclin-1↑,
*ROS↓, by their actions to reduce BACE1 activity, Aβ fibrillation, ROS damage, inflammation
*GutMicro↑, impact on the microbiome may be an additional contribution to reducing AD risk
*Risk↓,
*neuroP↑, deficiency impairs memory and learning in AD. RA acts as a neuroprotective agent by regulating gene expression, and neuronal survival
memory↑,
*Inflam↓, VA deficiency is also associated with elevated inflammatory cytokines, promoting neuroinflammation involved in AD progression
*neuroG↑, RA also stimulates adult neurogenesis, potentially influencing cognition in AD [17].
*cognitive↑,
*Aβ↓, It also influences Aβ clearance and tau phosphorylation, key pathological features of AD [19].
p‑tau↓,
*BACE↓, VA deficiency enhances BACE1 activity, increasing Aβ production and promoting neurotic plaque formation, a hallmark of AD pathology [21]
*Risk↓, Its deficiency disrupts glucose metabolism, impairs neurotransmitter production and DNA synthesis, and increases the risk of AD and neurological deficits
*GlucoseCon↑,
*cognitive↑, Thiamine supplementation, especially benfotiamine, has been shown to improve cognitive function in mild AD, while higher dietary intake supports cognitive impairments
*ATP↑, Low thiamine impairs glucose metabolism, reducing ATP production and increasing ROS, leading to mitochondrial and synaptic dysfunction, key features of AD.
*ROS↓,
*NADPH↑, Thiamine aids in producing ribose-5-phosphate and NADPH, essential for nucleotide synthesis.
*Aβ↓, Low thiamine reduces antioxidant capacity, leading to ROS accumulation and oxidative damage to proteins, lipids, and DNA. This triggers neurodegeneration processes, including development of Aβ plaques
*APP↓, The increase in APP activates beta-site APP cleaving enzymes-1 (BACE1), promoting its cleavage and enhancing the secretion of the Aβ monomers.
*BACE↓,
*antiOx↑, antioxidant properties of vitamin B12 are discussed to be accomplished by different mechanisms, including direct scavenging of ROS, particularly superoxide in the cytosol and mitochondria
*ROS↓,
*GSH↑, indirectly stimulating ROS scavenging by preservation of glutathione [
*Inflam↓, vitamin B12 might protect against inflammation-induced oxidative stress by modulating cytokine and growth factor production, including interleukin-6, tumour necrosis factor alpha (TNF-α) and epidermal growth factor.
*IL6↓,
*TNF-α↓,
*other↑, Vitamin B12 is an important cofactor of methionine-synthase, converting homocysteine into methionine.
*other↑, A folate and/or vitamin B12 deficiency with a reduction in genomic and non-genomic methylation processes caused by folate and/or vitamin B12 deficiency, might lead to decreased DNA stability
*other↑, methionine metabolism strongly depends on three important cofactors, namely, folate (vitamin B9), vitamin B6 and vitamin B12.
*Aβ↓, elevation of Aβ deposits in the hippocampus and cortex of an AD mouse model fed with a folate/vitamin B6/vitamin B12-deficient diet.
*memory↑, The simultaneous supplementation of folate and vitamin B12 attenuated the hyperhomocysteinemic-induced changes in APP processing and improved memory in these rats.
*p‑tau↓, Supplementation of folate and vitamin B12 also revealed positive effects on Aβ level and tau hyperphosphorylation in the retina of hyperhomocysteinemic three- to four-month-old rats
*APP↓, Notably, this increase in the APP, PS1 and BACE1 protein levels could be reverted by folate/vitamin B12 supplementation.
*BACE↓,
*ATP↑, C. elegans receiving a vitamin B12-containing diet showed a higher ATP level, decreased mitochondrial fragmentation and reduced oxidative species (ROS) than those without vitamin B12.
*neuroP↑, Significant neuroprotective effects of vitamin B12 were already apparent at 2 µM vitamin B12
*cognitive↑, dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex;
*NAD↑, Evidence shows that NR treatment increases intracellular NAD+ concentration and improves NAD+-dependent activities in the cell
*BACE↓, BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos
*Aβ↓, thus preventing Aβ production in the brain.
*PGC-1α↑, NR might reduce the Aβ burden in AD brain via enhancing PGC-1α expression, which increases BACE1 ubiquitination, degradation, and improves mitochondrial metabolism
*memory↑, Oral supplementation with nicotinamide riboside can inhibit the accumulation of pathological hallmarks of Alzheimer's disease and improve learning and memory in various murine models for dementia
*DNAdam↓, Nicotinamide riboside can also reduce DNA damage, neuroinflammation, apoptosis, and improved hippocampal synaptic plasticity in diabetic mice, and another Alzheimer's disease mouse model.
*Inflam↓,
*Apoptosis↓,
*cognitive↑, The cognitive benefits of nicotinamide riboside in Alzheimer's disease models may be modulated in part by upregulation of proliferator-activated-γ coactivator 1α-mediated β-secretase 1(BACE-1) ubiquitination and degradation, preventing Aβ production
*BACE↓,
*Aβ↓,
*BBB↑, Nicotinamide riboside also maintained blood-brain barrier integrity and maintained the gut microbiota in a mouse model for cerebral small vessel disease and alcohol-induced depression, respectively.
*GutMicro↑,
*eff↑, Oral nicotinamide riboside has been shown to be bioavailable and well tolerated in humans with limited adverse effects compared to other NAD+ precursors.
*cognitive↑, The combination of VD and RSV significantly increased time spent in target quadrant and the number of crossing via MWM test
*Aβ↓, In hippocampus, the combined intervention significantly reduced soluble Aβ42 level and BACE1 protein expression
*BACE↓,
*p‑tau↓, combined treatment significantly reduced phosphorylation of tau at serine404 and p-p53, as well as enhanced p-CREB protein expression
*p‑CREB↑,
*p‑NF-kB↓, The combination also significantly reduced GFAP and p-NFκB p65 in both hippocampus and cortex
*neuroP↑, combined intervention might exert greater neuroprotective effects in SAMP8 mice,
Showing Research Papers: 1 to 48 of 48
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 48
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
ROS↑, 2,
Cell Death ⓘ
p‑Akt↓, 1, Apoptosis↑, 3, BAX↑, 1, Bcl-2↓, 1, Bcl-2↑, 1, Casp1↑, 1, Casp3↑, 1, cl‑Casp3↑, 1,
DNA Damage & Repair ⓘ
DNAdam↑, 1,
Cell Cycle & Senescence ⓘ
P21↑, 1, TumCCA↑, 3,
Proliferation, Differentiation & Cell State ⓘ
EMT↓, 1, GSK‐3β↓, 1, mTOR↓, 1, PI3K↓, 1, TOP2↓, 1, TumCG↓, 1,
Migration ⓘ
E-cadherin↓, 1, LRP1↑, 1, MMP2↓, 2, MMP9↓, 1, MMPs↓, 1, RAGE↓, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 1, TumMeta↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 1, EGFR↓, 1, Hif1a↓, 1, VEGF↓, 1,
Barriers & Transport ⓘ
P-gp↓, 1, P-gp⇅, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, NF-kB↓, 1, TNF-α↓, 1,
Synaptic & Neurotransmission ⓘ
p‑tau↓, 1,
Protein Aggregation ⓘ
BACE↓, 2,
Drug Metabolism & Resistance ⓘ
BioEnh↑, 1, ChemoSen↑, 1, Dose↝, 1, eff↑, 2, RadioS↑, 1,
Clinical Biomarkers ⓘ
EGFR↓, 1, RAGE↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 1, chemoPv↑, 1, memory↑, 2,
Total Targets: 50
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 18, Catalase↑, 2, GPx↑, 3, GSH↑, 7, GSSG↓, 1, GSTs↑, 1, HO-1↑, 6, lipid-P↓, 8, MDA↓, 9, MPO↓, 2, NQO1↑, 3, NRF2↓, 1, NRF2↑, 8, PARK2↑, 1, ROS↓, 29, SIRT3↑, 1, SOD↑, 10, SOD1↑, 1, TAC↑, 1, TrxR↑, 2,
Metal & Cofactor Biology ⓘ
IronCh↑, 1, TfR1/CD71↓, 1,
Mitochondria & Bioenergetics ⓘ
ATP↑, 5, Insulin↑, 1, mtDam↓, 1, PGC-1α↓, 1, PGC-1α↑, 2,
Core Metabolism/Glycolysis ⓘ
Acetyl-CoA↓, 1, AMPK↑, 5, CREB↓, 1, CREB↑, 2, p‑CREB↑, 3, FAO↑, 1, GlucoseCon↑, 1, LDL↓, 2, NAD↑, 1, NADPH↓, 1, NADPH↑, 1, PPARγ↓, 1, PPARγ↑, 2, SIRT1↑, 4,
Cell Death ⓘ
Akt↓, 1, Akt↑, 2, p‑Akt↓, 1, p‑Akt↑, 1, Apoptosis↓, 3, BAX↓, 2, Bax:Bcl2↓, 2, Bcl-2↑, 1, Casp3↓, 1, cl‑Casp3↓, 1, Casp9↑, 1, iNOS↓, 8, MAPK↓, 1, MAPK↑, 1,
Transcription & Epigenetics ⓘ
Ach↑, 1, other↓, 6, other↑, 3,
Protein Folding & ER Stress ⓘ
ER Stress↓, 1, GRP78/BiP↑, 1, HSP70/HSPA5↑, 3, UPR↑, 1,
Autophagy & Lysosomes ⓘ
Beclin-1↑, 1, MitoP↑, 1,
DNA Damage & Repair ⓘ
DNAdam↓, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↓, 1, ERK↑, 1, p‑ERK↑, 1, FOXO3↑, 1, GSK‐3β↓, 3, mTOR↓, 2, neuroG↑, 1, PI3K↓, 1, PI3K↑, 2, p‑STAT3↓, 1,
Migration ⓘ
AntiAg↑, 1, APP↓, 8, Ca+2↓, 3, cal2↓, 1, CDK5↓, 1, LRP1↑, 1, MMP9↓, 3, PKA↑, 2, p‑SMAD2↓, 1, SPARC↓, 1, TXNIP↓, 1, ZO-1↓, 1,
Angiogenesis & Vasculature ⓘ
NO↓, 2, VEGF↑, 1,
Barriers & Transport ⓘ
BBB↑, 9,
Immune & Inflammatory Signaling ⓘ
COX2↓, 6, IFN-γ↓, 1, IL10↑, 1, IL17↓, 1, IL1β↓, 10, IL23↓, 1, IL33↓, 1, IL6↓, 9, IL8↓, 1, Inflam↓, 19, Inflam↑, 1, MCP1↓, 2, MyD88↓, 1, NF-kB↓, 9, p‑NF-kB↓, 2, PGE2↓, 1, TLR2↓, 1, TLR4↓, 1, TNF-α↓, 10,
Synaptic & Neurotransmission ⓘ
AChE↓, 13, ADAM10↑, 2, BChE↓, 3, BDNF↑, 7, ChAT↑, 1, MAOA↓, 2, PSD95↑, 1, tau?, 1, tau↓, 2, p‑tau↓, 15, TrkB↑, 1,
Protein Aggregation ⓘ
AEP↓, 1, Aβ↓, 34, BACE↓, 46, IDE↑, 2, MAOB↓, 2, NEP↑, 1, NLRP3↓, 4, PP2A↑, 3,
Hormonal & Nuclear Receptors ⓘ
CYP19↓, 1, ER(estro)↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 3, BioAv↑, 3, BioAv↝, 1, Dose↝, 2, eff↑, 6, Half-Life↑, 1, Half-Life↝, 2,
Clinical Biomarkers ⓘ
ALP↓, 1, AST↓, 1, BloodF↑, 1, BP∅, 1, GutMicro↑, 2, IL6↓, 9,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiDiabetic↑, 2, cardioP↑, 2, cognitive↑, 27, hepatoP↑, 2, memory↑, 23, Mood↑, 2, motorD↑, 1, neuroP↑, 28, Obesity↓, 1, OS↑, 2, RenoP↑, 2, Risk↓, 2, STEP↓, 1, Strength↑, 1, toxicity↓, 3, toxicity∅, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1, IRF3↓, 1,
Total Targets: 163
Scientific Paper Hit Count for: BACE, β-site APP-cleaving enzyme
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#:1349 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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