| Source: |
| Type: |
| Power to enhance an anti cancer effect |
| 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. - cerebrospinal fluid (CSF) TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals. (gut microbes enzymatically generate trimethylamine (TMA) from choline or l-carnitine). - AD models and human tissue studies show an imbalance toward mitochondrial fission, involving increased DRP1 and FIS1 and reduced fusion proteins such as MFN1, MFN2, and OPA1. Usually increased or overactive in AD-like pathology -↓ Reduced miR-106b-5p has been reported in peripheral blood from Alzheimer's disease patients and has been investigated as a potential circulating biomarker. -Glutaminyl cyclase (QC/QPCT)↑ : because it can increase formation of pyroglutamate Aβ -GFAP↑ : Elevated GFAP is observed in affected brain regions and increased circulating GFAP is strongly associated with cerebral amyloid pathology and progression toward cognitive impairment. -ODC1↑ : Experimental inhibition of astrocytic ODC1 reduces aberrant GABA production, improves memory deficits, and can markedly reduce hippocampal Aβ plaque burden in APP/PS1 models. -H₂S signaling in Alzheimer’s disease: Generally ↓. AD is associated with reduced brain H₂S production, ↓ CSE/CTH expression, and particularly ↓ protein persulfidation. Reduced GSK3β persulfidation increases GSK3β activity and favors Tau hyperphosphorylation. -↓ Reduced synaptophysin is a well-established marker of presynaptic and synaptic loss in Alzheimer's disease. -↑ Increased 3-nitrotyrosine(3-NT) and protein tyrosine nitration are well-established indicators of oxidative and nitrosative stress in Alzheimer's disease. -↑ Increased peroxynitrite formation (ONOO) and nitrosative stress are associated with Alzheimer's disease. - salivary lactoferrin tends to be decreased in AD in several studies 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). -↓ SYN3 expression has been reported in hippocampal CA1 pyramidal neurons in mild cognitive impairment and Alzheimer's disease 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 Acetyl-L-carnitine, ALA, Apigenin, Anthocyanins Blueberrys, Aromatherapy, Artemisinin, Ashwagandha, β-carotene(vitamin A), Bacopa monnieri, Baicalein, Baicalin, Berberine, Betulinic acid, Boron, Boswellia (frankincense), Caffeic acid, Caffeine, Capsaicin, Carnosine, Carnosic acid, Chlorogenic acid, Choline (note U shaped dose curve-target 350mg/day), Chrysin, Cinnamon, CoQ10, Crocetin, Curcumin, dietMed, dietMet, dietSTF, EGCG, Ellagic acid, Exercise, Ferulic Acid, Fisetin, Flav, FLS, Folic Acid (5-MTHF, L-methylfolate)-reduce homocysteine, Galantamine, Ginger, Ginkgo biloba, Ginseng, Honokiol, Huperzine A, hydrogen gas, Lactoferrin, Lecithin, Licochalcone A, Lutein, Luteolin, Lycopene, M-Blu, Moringa oleifera, Mushroom Lion’s Mane, MSM, MCToil, NAD, Naringenin, PEMF, Piperine, Phenylbutyrate, Phosphatidylserine, Piperlongumine, Potassium, probiotics, Propolis, Pterostilbene, Quercetin, Resveratrol, Rivastigmine, Rosmaric Acid(reduce copper-induced neurotoxicity), Rutin, Safflower yellow, Sage, SAMe, selenium, Serotonin, Shankhpushpi, Shikonin, Shilajit/Fulvic Acid, silicon(reduce Alum bioavialability), Silymarin (Milk Thistle) silibinin, Sulforaphane, Taurine, TQ, Ursolic Acid Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B12, Vitamin E, Vitamin D, Vitamin K2 Zeaxanthin, zinc, 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. |
| 6461- | 1,8-Cin, | 1,8-cineole (eucalyptol): A versatile phytochemical with therapeutic applications across multiple diseases |
| - | Review, | AD, | NA | - | Review, | Var, | NA |
| 6462- | 1,8-Cin, | Modes of Action of 1,8-Cineol in Infections and Inflammation |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 3941- | 5HT, | dietMed, | VitB12, | FA, | VitC | Nutrition strategies that improve cognitive function |
| - | Review, | AD, | NA |
| 3968- | ACNs, | Enhanced Neuronal Activation with Blueberry Supplementation in Mild Cognitive Impairment |
| - | Human, | AD, | NA |
| 3973- | ACNs, | Saskatoon and wild blueberries have higher anthocyanin contents than other Manitoba berries |
| - | Analysis, | AD, | NA |
| 2660- | AL, | Allicin: A review of its important pharmacological activities |
| - | Review, | AD, | NA | - | Review, | Var, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 3443- | ALA, | Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 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 |
| 7839- | AO, | ISQ, | The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model |
| - | in-vivo, | AD, | NA | - | in-vivo, | Obesity, | NA |
| 3817- | Aroma, | Therapeutic potential of aromatic plant extracts in Alzheimer's disease: Comprehensive review of their underlying mechanisms |
| - | Review, | AD, | NA |
| 4804- | ASTX, | Astaxanthin in cancer therapy and prevention (Review) |
| - | Review, | Var, | NA | - | 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 |
| 5633- | BCA, | Mechanisms Behind the Pharmacological Application of Biochanin-A: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 5561- | betaCar, | Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer’s Disease |
| - | Review, | AD, | NA |
| 5563- | betaCar, | Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer's Disease |
| - | Review, | AD, | NA |
| 3987- | betaCar, | Lyco, | Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection |
| - | Trial, | AD, | NA |
| 3988- | betaCar, | Lut, | Zeax, | Effects of egg consumption on carotenoid absorption from co-consumed, raw vegetables |
| - | Trial, | AD, | NA |
| 5656- | BNL, | Role of borneol as enhancer in drug formulation: A review |
| - | Review, | Nor, | NA | - | Review, | Stroke, | NA | - | Review, | AD, | NA |
| 5666- | BNL, | Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider |
| - | in-vivo, | AD, | NA |
| 5669- | BNL, | Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 2775- | Bos, | The journey of boswellic acids from synthesis to pharmacological activities |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | PSA, | NA |
| 6542- | BSB, | Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol |
| - | Review, | Var, | NA | - | Review, | Park, | NA | - | Review, | AD, | NA |
| - | Analysis, | AD, | NA |
| - | Study, | AD, | NA |
| 7515- | CA, | Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model |
| - | in-vivo, | AD, | NA |
| 5756- | CA, | Experimental Evidence of Caffeic Acid’s Neuroprotective Activity in Alzheimer’s Disease: In Vitro, In Vivo, and Delivery-Based Insights |
| - | vitro+vivo, | AD, | NA |
| 5860- | CAP, | Beneficial Effects of Capsaicin in Disorders of the Central Nervous System |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 5927- | CAR, | Neuroprotective Potential and Underlying Pharmacological Mechanism of Carvacrol for Alzheimer’s and Parkinson’s Diseases |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 5926- | CAR, | An Updated Review of Research into Carvacrol and Its Biological Activities |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Asthma, | NA |
| 3869- | Carno, | Carnosine, Small but Mighty—Prospect of Use as Functional Ingredient for Functional Food Formulation |
| - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 6656- | Cen, | Recent insights into therapeutic potential and nanostructured carrier systems of Centella asiatica: An evidence-based review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 6649- | Cen, | Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action |
| - | in-vivo, | AD, | NA |
| 6016- | CGA, | Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Diabetic, | 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 |
| 6038- | CGA, | Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices |
| - | in-vivo, | AD, | NA | - | in-vivo, | Stroke, | NA |
| 6037- | CGA, | Pharmacokinetics and brain penetration study of chlorogenic acid in rats |
| - | in-vivo, | AD, | NA | - | in-vivo, | Stroke, | NA |
| 6034- | CGA, | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| - | in-vivo, | AD, | NA |
| - | 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 |
| 6107- | Chol, | Choline supplements: An update |
| - | Review, | AD, | NA |
| 6111- | Chol, | The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease |
| - | Human, | AD, | NA |
| 6113- | Chol, | Association between choline supplementation and Alzheimer’s disease risk: a systematic review protocol |
| - | Review, | AD, | NA |
| 6108- | Chol, | Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health |
| - | Review, | Nor, | NA | - | Review, | AD, | NA |
| 6121- | Chol, | Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial |
| - | Human, | AD, | NA |
| 3701- | Chol, | Lifelong choline supplementation ameliorates Alzheimer's disease pathology and associated cognitive deficits by attenuating microglia activation |
| - | in-vivo, | AD, | NA |
| 3704- | Chol, | Acetylcholine, aging, and Alzheimer's disease |
| - | Review, | AD, | NA |
| 6135- | CHr, | Chrysin as a Multifunctional Therapeutic Flavonoid: Emerging Insights in Pathogenesis Management: A Narrative Review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 3891- | Cin, | Identification of potential targets of cinnamon for treatment against Alzheimer's disease-related GABAergic synaptic dysfunction using network pharmacology |
| - | Analysis, | 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#:961 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid