| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 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 NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Acetyl-L-carnitine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">ALA, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Apigenin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Anthocyanins Blueberrys, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Aromatherapy, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Artemisinin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ashwagandha, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">β-carotene(vitamin A), NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Bacopa monnieri, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Baicalein, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Baicalin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Berberine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Betulinic acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Boron, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Boswellia (frankincense), NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Caffeic acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Caffeine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Capsaicin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Carnosine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Carnosic acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Chlorogenic acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Choline, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Chrysin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Cinnamon, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">CoQ10, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Crocetin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Curcumin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietMed, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietMet, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">dietSTF, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">EGCG, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ellagic acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Exercise, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ferulic Acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Fisetin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Flav, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">FLS, NRF2&w20=Catalase &w21=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, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Galantamine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginger, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginkgo biloba, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ginseng, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Honokiol, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Huperzine A, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">hydrogen gas, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lecithin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lutein, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Luteolin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Lycopene, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">M-Blu, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Moringa oleifera, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Mushroom Lion’s Mane, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">MSM, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">MCToil, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">NAD, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Naringenin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">PEMF, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Piperine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Phenylbutyrate, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Phosphatidylserine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Piperlongumine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Potassium, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">probiotics, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Propolis, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Pterostilbene, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Quercetin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Resveratrol, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rivastigmine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rosmaric Acid(reduce copper-induced neurotoxicity), NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Rutin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Safflower yellow, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Sage, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">SAMe, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">selenium, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Serotonin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shankhpushpi, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shikonin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Shilajit/Fulvic Acid, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">silicon(reduce Alum bioavialability), NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Silymarin (Milk Thistle) silibinin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Sulforaphane, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Taurine, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">TQ, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Ursolic Acid NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B1, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B2, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B3, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B5, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B6, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin B12, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin E, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin D, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Vitamin K2 NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">Zeaxanthin, NRF2&w20=Catalase &w21=GSH&w22=SOD&w23=HO-1&w24=PGE2&w25=Inflam&w26=NF-kB&w27= IL1β&w28=TNF-α">zinc, NRF2&w20=Catalase &w21=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. |
| 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 |
| 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 |
| 3449- | ALA, | Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells |
| - | in-vitro, | AD, | SK-N-BE |
| 3539- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3550- | ALA, | Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease? |
| - | Review, | AD, | NA |
| 4280- | Api, | Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 4804- | ASTX, | Astaxanthin in cancer therapy and prevention (Review) |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 5425- | ASTX, | Multiple roles of fucoxanthin and astaxanthin against Alzheimer's disease: Their pharmacological potential and therapeutic insights |
| - | in-vivo, | AD, | NA |
| 5508- | Ba, | Neuroprotective effects of baicalin and baicalein on the central nervous system and the underlying mechanisms |
| - | Review, | Stroke, | NA | - | Review, | Park, | NA | - | Review, | AD, | NA |
| 2626- | Ba, | Molecular targets and therapeutic potential of baicalein: a review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3678- | BBR, | Network pharmacology study on the mechanism of berberine in Alzheimer’s disease model |
| - | Review, | AD, | NA |
| 5633- | BCA, | Mechanisms Behind the Pharmacological Application of Biochanin-A: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 3866- | Bos, | Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties |
| - | Review, | AD, | NA |
| 2775- | Bos, | The journey of boswellic acids from synthesis to pharmacological activities |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | PSA, | NA |
| 2768- | Bos, | Boswellic acids as promising agents for the management of brain diseases |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 2772- | Bos, | Mechanistic role of boswellic acids in Alzheimer’s disease: Emphasis on anti-inflammatory properties |
| - | Review, | AD, | 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 |
| 5926- | CAR, | An Updated Review of Research into Carvacrol and Its Biological Activities |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | asthmatic, | 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 |
| 6040- | CGA, | Protective effect of chlorogenic acid on cognitive impairment in rats with early Alzheimer's disease via Wnt signaling pathway |
| - | in-vivo, | AD, | NA |
| 6001- | Chit, | Recent advances in engineering chitosan-based nanoplatforms in biotherapeutic multi-delivery for multi-targeted disease treatments: Promises and outlooks |
| - | Review, | Var, | HepG2 | - | Review, | AD, | NA |
| 5798- | CRMs, | Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders |
| - | Review, | Nor, | NA | - | Review, | AD, | NA |
| 3794- | CUR, | Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities |
| - | Review, | AD, | NA |
| 3795- | CUR, | Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence |
| - | Review, | AD, | NA |
| 3581- | CUR, | Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer's Disease |
| - | NA, | AD, | NA |
| 3576- | CUR, | Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease |
| - | 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 |
| 3778- | FA, | Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review |
| - | Review, | AD, | NA |
| 3714- | FA, | Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review |
| - | Review, | AD, | NA |
| 4302- | Gins, | Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease |
| - | Review, | AD, | NA |
| 3770- | H2, | Role of Molecular Hydrogen in Ageing and Ageing-Related Diseases |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3761- | H2, | Therapeutic Inhalation of Hydrogen Gas for Alzheimer's Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study |
| - | Human, | AD, | NA |
| 3767- | H2, | The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges |
| - | Review, | 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 |
| 2894- | HNK, | Pharmacological features, health benefits and clinical implications of honokiol |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 4292- | LT, | Luteolin for neurodegenerative diseases: a review |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | MS, | NA | - | Review, | Stroke, | NA |
| 2916- | LT, | Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3532- | Lyco, | Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer’s disease |
| - | 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 |
| 4230- | Lyco, | Supplementation of lycopene attenuates oxidative stress induced neuroinflammation and cognitive impairment via Nrf2/NF-κB transcriptional pathway |
| - | in-vivo, | AD, | NA |
| 4228- | Lyco, | A review for the pharmacological effect of lycopene in central nervous system disorders |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 4105- | MF, | Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases |
| - | Review, | AD, | 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#:226 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid