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| Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress. Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system. cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment. While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied. Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy. Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death. Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion. Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS). "...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..." "Cancer cells have a high level of GSH compared to normal cells." "...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy." The loss of GSH is broadly known to be directly related to the apoptosis progression. |
| In Alzheimer's disease (AD), cholinergic dysfunction (often with reduced acetylcholine tone and impaired choline metabolism) is linked with cortical dysfunction, memory deficit, abnormal cerebral blood flow, task learning difficulty, sleep-cycle disruption, and neurodevelopmental effects (context-dependent). CORE HALLMARKS / HIGH-CONFIDENCE AXES: - tau and Aβ, their accumulation in AD brains is known to be a major hallmark. In AD, PP2A↓ activity is decreased (reported), contributing to hyperphosphorylated tau accumulation. SIRT-1↓ levels in AD brains are associated with accumulation of Aβ and tau (reported). - glucose metabolism↓ (brain glucose hypometabolism) occurs in AD long before significant clinical signs in many cohorts/models (reported). - Neuroinflammation / lipid mediator tone (reported): 5-LOX↑ and PGE2↑ (model-/region-dependent). - Synaptic vulnerability (reported): PSD95↓ in hippocampus and cortex; restoring PSD95 shows cognitive benefits in models. - Clearance/transport imbalance (reported): IDE↓, NEP↓, LRP1↓, and AEP↑ protein levels in AD brains (reported). COMMONLY REPORTED DIRECTIONAL CHANGES (model/region/compartment dependent): - Monoamines (reported): concentrations of 5-HTP↓, 5-HT(seratonin)↓, and 5-HIAA↓ are lower in Alzheimer's patients (varies by region/study). - Cholinergic system (clinical target): reduction in ACh↓ production; ChAT↓ activity reduced (synthesizes ACh). - Four key enzymes frequently targeted in AD symptom/adjunct strategies: AChE, BChE, MAOA, MAOB (objective inhibit). - Neurotrophic tone (reported): BDNF↓ in key regions. - Stress can decrease expression of brain-derived neurotrophic factor (BDNF). - Kinase/protease stress (reported): CDK5↑ hyperactivation; calpain↑ overactivated by increased intracellular Ca²⁺ → p-tau and aggregation. - Aβ-linked synaptic regulator (reported): STEP↑ upregulated largely due to Aβ oligomer accumulation. - α-secretase axis (reported): ADAM10↓ downregulated in AD brains. - Metabolic cofactors (reported): ALC↓ (ALCAR); Homocarnosine↓ (CSF declines with age); possible low Taurine↓ (age-related + dementia reports). - Ion/glutamate handling (reported): impaired glutamate clearance + depressed Na+/K+ ATPase → cellular ion imbalance risk. - Aging reduces NAD⁺↓ (in AD depletion may be more severe). - Mitochondrial capacity axis (reported): PGC-1↓ decreased in Alzheimer’s brains. - Innate immune DNA-sensing axis (animal): cGAS–STING↑ elevation observed in AD mice and normalized by NR treatment. - Vascular/structure (reported): a profound change in BBB permeability; progressive brain shrinkage (atrophy). - Glycation axis (reported): AGEs↑ and RAGE↑ expression. HOMOCYSTEINE / B-VITAMIN AXIS: - Raised plasma total homocysteine (tHcy)↑ associated with cognitive impairment, AD, or vascular dementia (epidemiology). - Homocysteine can build up if vitamin B6, B12, or folate levels are low. - Homocysteine and B-vitamin in Cognitive Impairment (VITACOG) study. - Vit B6 might be an important B vitamin (often discussed along with B12 and folate). - Thiamine↓ deficiency produces a cholinergic deficit (well-aligned with AD features). - Decreased thiamine (B1) in AD may exacerbate Aβ deposition, tau hyperphosphorylation, and oxidative stress (reported). MICRONUTRIENTS / CAROTENOIDS (reported; compartment-dependent): - vitamin A↓ and β-carotene↓ lower in some AD cohorts; excess retinol may contribute to osteoporosis risk. - Diminished circulating vitamin E↓ reported in AD. - Vitamin B5↓ in multiple brain regions (reported). - Trace elements: patients with AD reported lower serum Se, Cu, and Zn↓ (serum findings vary by study). - Brain metals: some studies report higher brain copper↑ and iron↑ in specific regions/structures; compartment and region matter. Rosmarinic acid reported to reduce copper-induced neurotoxicity in vitro/in vivo and may interfere with amyloid–copper interactions (preclinical). - SAMe↓ concentrations in CSF reported in AD. - MPOD often reduced in AD patients. - AD brains reported lower levels of lutein↓, zeaxanthin↓, anhydrolutein↓, (VitA)retinol↓, lycopene↓, alpha-tocopherol↓. RISK CONTEXT: - Apolipoprotein E4 (ApoE4) genotype is the strongest known genetic risk factor for late-onset AD. - One copy of ApoE4: ~3–4× increased risk (range varies by cohort). - Two copies: ~8–12× increased risk (range varies). - VitK lower in circulating blood of APOE4 carriers (reported). - Type 2 diabetes, traumatic brain injury, stroke, diet, and above all, aging is the number ONE risk factor. Treatments / Strategy Targets (high-level): - Early intervention tends to have a greater positive effect than interventions during middle or late stages. - BOLD fMRI imaging can be used to observe brain activity via blood oxygen/flow changes. - Reduce ROS and inflammation in the brain (context-dependent; avoid over-suppressing adaptive signaling). - Inhibiting acetylcholinesterase (AChE) (which breaks down ACh), e.g., donepezil, rivastigmine. - Natural AChE inhibitors include: Berberine, Luteolin, Crocetin(saffron), Querctin, TQ - Natural AChE inhibitors in database (check BBB pass potential). - MAOB inhibitors, APP inhibitors, PGE2 inhibitors, NLRP3 inhibitors, BACE inhibitors - BDNF activators, PSD95 activator - STEP, ADAM10 - Diets with an adequate ratio (5:1) of omega-6:3 (Mediterranean diet). - Vitamins B1, B6, B12, B9 (folic acid) and D, choline, iron and iodine exert neuroprotective effects (general nutrition framing). - Antioxidants (vitamins C, E, A, zinc, selenium, lutein and zeaxanthin). - Fiber may promote gut microbiome diversity influencing brain health. - Supplementing with NAD⁺ precursors (NR or NMN) improves cognition and reduces amyloid/tau pathologies in AD mice (animal evidence). - "It is advisable to consume diets with an adequate ratio (5:1) of omega-6:3 fatty acids (Mediterranean diet) ... antioxidants ... role in oxidative stress ... cognition." Nutrition Strategies - Reduction of cognitive decline may be achieved by following a healthy dietary pattern limiting added sugars while maximizing fish, fruits, vegetables, nuts, seeds. SeNPs may also be useful as a Drug Delivery System. Related Pathways to research in this database (products that modulate them): - neuroprotective, cognitive, memory - Aβ aggregation, Tau↓, AChE↓, ACh↑, ChAT↑, acetyl-CoA↑, BDNF↑, BACE↓, NLRP3↓, PSD95↑, PGE2↓, homoC↓ - Increasing AntiOxidants: Catalase↑, GSH↑, SOD↑, HO-1↑, to decrease ROS↓ - Lower Inflammation: TNF-α↓, IL1β↓, IL6↓ Natural Products that may benefit AD. -Some key pathways are highlighted in RED in the following links GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Acetyl-L-carnitine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">ALA, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Apigenin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Anthocyanins Blueberrys, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Aromatherapy, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Artemisinin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ashwagandha, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">β-carotene(vitamin A), GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Bacopa monnieri, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Baicalein, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Baicalin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Berberine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Betulinic acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Boron, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Boswellia (frankincense), GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Caffeic acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Caffeine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Capsaicin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Carnosine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Carnosic acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Chlorogenic acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Choline, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Chrysin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Cinnamon, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">CoQ10, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Crocetin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Curcumin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietMed, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietMet, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietSTF, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">EGCG, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ellagic acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Exercise, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ferulic Acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Fisetin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Flav, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">FLS, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Folic Acid (5-MTHF, L-methylfolate)-reduce homocysteine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Galantamine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginger, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginkgo biloba, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginseng, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Honokiol, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Huperzine A, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">hydrogen gas, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lecithin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lutein, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Luteolin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lycopene, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">M-Blu, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Moringa oleifera, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Mushroom Lion’s Mane, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">MSM, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">MCToil, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">NAD, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Naringenin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">PEMF, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Piperine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Phenylbutyrate, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Phosphatidylserine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Piperlongumine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Potassium, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">probiotics, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Propolis, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Pterostilbene, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Quercetin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Resveratrol, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rivastigmine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rosmaric Acid(reduce copper-induced neurotoxicity), GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rutin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Safflower yellow, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Sage, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">SAMe, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">selenium, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Serotonin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shankhpushpi, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shikonin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shilajit/Fulvic Acid, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">silicon(reduce Alum bioavialability), GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Silymarin (Milk Thistle) silibinin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Sulforaphane, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Taurine, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">TQ, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ursolic Acid GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B1, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B2, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B3, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B5, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B6, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B12, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin E, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin D, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin K2 GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Zeaxanthin, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">zinc, GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Aluminium has a negative impact on cognition but silicon can decrease Alumunium bioavailability, and Vitamin K2 may provide some protection. Example So does RMF Brain Energy Systems Matrix (AD)Tier 1–2 as “core metabolic cofactors / redox pools”Tier 4 as “alternative fuels / bypass strategies” Tier 5–6 as “capacity + delivery constraints” (often explains why supplements don’t translate)
TSF (Time-Scale Flag): P = 0–30 min, R = 30 min–3 hr, G = >3 hr (adaptation/phenotype). Evidence: "Strong (human)" = consistent clinical/epidemiologic support; "Moderate" = mixed but plausible human signals; "Emerging" = early-stage human; "Mechanistic" = preclinical/biochemical rationale. |
| 3972- | ACNs, | Recent Research on the Health Benefits of Blueberries and Their Anthocyanins |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 2558- | AL, | Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment |
| - | Review, | AD, | NA |
| 2657- | AL, | Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases |
| - | Review, | CardioV, | NA | - | Review, | AD, | NA |
| 2660- | AL, | Allicin: A review of its important pharmacological activities |
| - | Review, | AD, | NA | - | Review, | Var, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 3269- | ALA, | Sulfur-containing therapeutics in the treatment of Alzheimer’s disease |
| - | NA, | AD, | NA |
| 3270- | ALA, | Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis |
| - | Trial, | AD, | NA |
| 3271- | ALA, | Decrypting the potential role of α-lipoic acid in Alzheimer's disease |
| - | Review, | AD, | NA |
| 3272- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3438- | ALA, | The Potent Antioxidant Alpha Lipoic Acid |
| - | Review, | NA, | NA | - | Review, | AD, | NA |
| 3447- | ALA, | Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells |
| - | in-vitro, | AD, | SH-SY5Y |
| 3539- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3543- | ALA, | The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease |
| - | Study, | AD, | NA |
| 3547- | ALA, | Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3545- | ALA, | Potential therapeutic effects of alpha lipoic acid in memory disorders |
| - | Review, | AD, | NA |
| 3544- | ALA, | Alpha lipoic acid for dementia |
| - | Review, | AD, | NA |
| 297- | ALA, | Insights on the Use of α-Lipoic Acid for Therapeutic Purposes |
| - | Review, | BC, | SkBr3 | - | Review, | neuroblastoma, | SK-N-SH | - | Review, | AD, | NA |
| 4303- | Ash, | Ashwagandha (Withania somnifera)—Current Research on the Health-Promoting Activities: A Narrative Review |
| - | Review, | AD, | NA |
| 2605- | Ba, | BA, | Potential therapeutic effects of baicalin and baicalein |
| - | Review, | Var, | NA | - | Review, | Stroke, | NA | - | Review, | IBD, | NA | - | Review, | Arthritis, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 2689- | BBR, | Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells |
| - | in-vitro, | Nor, | PC12 | - | in-vitro, | AD, | NA | - | in-vitro, | Stroke, | NA |
| 3684- | BBR, | Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies |
| - | Review, | AD, | NA |
| - | in-vivo, | AD, | NA |
| 2731- | BetA, | Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives |
| - | Review, | GBM, | NA | - | Review, | Park, | NA | - | Review, | AD, | NA |
| 760- | Bor, | Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer’s Disease |
| - | in-vivo, | AD, | NA |
| 2775- | Bos, | The journey of boswellic acids from synthesis to pharmacological activities |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | PSA, | NA |
| 4263- | CA, | Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action |
| - | Review, | AD, | NA |
| 5768- | CAPE, | Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 5925- | CAR, | Neuroprotective effects of carvacrol against Alzheimer’s disease and other neurodegenerative diseases: A review |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 6002- | CGA, | Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials |
| - | Review, | Var, | NA | - | Review, | Diabetic, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 3637- | Cro, | Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment |
| - | NA, | AD, | NA |
| 3794- | CUR, | Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities |
| - | Review, | AD, | NA |
| 3751- | CUR, | Gala, | A Novel Galantamine-Curcumin Hybrid as a Potential Multi-Target Agent against Neurodegenerative Disorders |
| - | in-vivo, | AD, | NA |
| 3576- | CUR, | Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease |
| - | Review, | AD, | NA |
| 3574- | CUR, | The effect of curcumin (turmeric) on Alzheimer's disease: An overview |
| - | Review, | AD, | NA |
| 2818- | CUR, | Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/ GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways |
| - | Review, | AD, | NA |
| 4333- | Cyste, | Cystamine protects from 3-nitropropionic acid lesioning via induction of nf-e2 related factor 2 mediated transcription |
| - | vitro+vivo, | AD, | NA |
| 3782- | FA, | Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer’s disease-like pathology through Akt-ERK crosstalk pathway in male rats |
| - | in-vivo, | AD, | NA |
| 3723- | Gb, | Can We Use Ginkgo biloba Extract to Treat Alzheimer’s Disease? Lessons from Preclinical and Clinical Studies |
| - | Review, | AD, | NA |
| 3772- | H2, | Therapeutic potential of hydrogen-rich water in zebrafish model of Alzheimer’s disease: targeting oxidative stress, inflammation, and the gut-brain axis |
| - | in-vivo, | AD, | NA |
| 2872- | HNK, | Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis |
| - | in-vivo, | ALS, | NA | - | NA, | Stroke, | NA | - | NA, | AD, | NA | - | NA, | Park, | NA |
| 2904- | LT, | Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons |
| - | in-vitro, | Park, | SK-N-SH | - | in-vitro, | AD, | NA |
| 3528- | Lyco, | The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3268- | Lyco, | Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders |
| - | Review, | AD, | NA |
| 3264- | Lyco, | Pharmacological potentials of lycopene against aging and aging‐related disorders: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3848- | MSM, | Modulatory effect of methylsulfonylmethane against BPA/γ-radiation induced neurodegenerative alterations in rats: Influence of TREM-2/DAP-12/Syk pathway |
| - | in-vitro, | AD, | NA |
| 3251- | PBG, | The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways |
| - | Review, | AD, | NA | - | Review, | Diabetic, | NA | - | Review, | Var, | NA | - | in-vitro, | Nor, | H9c2 |
| 3587- | PI, | Piperine: A review of its biological effects |
| - | Review, | Park, | NA | - | Review, | AD, | NA |
| 3927- | PTS, | Effects of Pterostilbene on Cardiovascular Health and Disease |
| - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3924- | PTS, | Effect of resveratrol and pterostilbene on aging and longevity |
| - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 4296- | QC, | A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders |
| - | Review, | AD, | NA |
| 3607- | QC, | Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
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:38 Cells:% prod#:% Target#:137 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid