neuroP Cancer Research Results

neuroP, neuroprotective: Click to Expand ⟱
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Neuroprotective refers to the ability of a substance, intervention, or strategy to preserve the structure and function of nerve cells (neurons) against injury or degeneration.
-While cancer and neurodegenerative processes might seem distinct, there is significant overlap in terms of treatment-related neurotoxicity, shared molecular mechanisms, and the potential for therapies that provide neuroprotection during cancer treatment.
Scientific Papers found: Click to Expand⟱
4051- ,    Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women
- Study, AD, NA
*cognitive↑, The odds of IADL impairment increased significantly with decreasing intake of vitamins B2, B6, and B12
*neuroP↑, possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats, and B-group vitamins, and support dietary intervention to prevent cognitive decline.
*other↝, Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy dessert and ice-cream.
*other⇅, IADL impairment was associated with lower intake of vegetables

3970- ACNs,    Anthocyanin-rich blueberry extracts and anthocyanin metabolite protocatechuic acid promote autophagy-lysosomal pathway and alleviate neurons damage in in vivo and in vitro models of Alzheimer's disease
- in-vivo, AD, NA
*cognitive↑, Previous studies have found that cognitive impairment and neuronal damage were effectively alleviated by blueberry extract (BBE) in AD mice
*LDH↓, including decreased neuron viability and increased levels of lactate dehydrogenase and reactive oxygen species, was effectively reversed by PCA
*ROS↓,
*neuroP↑, proved PCA may be the main bioactive metabolite of BBE for neuroprotective effects, providing a basis for dietary intervention in AD.

3971- ACNs,    Blueberry Supplementation Improves Memory in Older Adults
- Human, AD, NA
*antiOx↑, Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects.
*Inflam↓,
*memory↑, anthocyanins have been associated with increased neuronal signaling in brain centers mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration.
*neuroP↑, preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit
*cognitive↑, At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list recall (p = 0.04).
*Mood↑, In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10)
*glucose↓,

3972- ACNs,    Recent Research on the Health Benefits of Blueberries and Their Anthocyanins
- Review, AD, NA - Review, Park, NA
*cardioP↑, Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection.
*neuroP↑,
*Inflam↓, Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function
*antiOx↓,
*GutMicro↑, Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health
*Half-Life↑, However, >50% of the 13C still remained in the body after 48 h
*LDL↓, controlled study of 58 diabetic patients, blueberry intake led to a decline in LDL cholesterol, triglycerides, and adiponectin and an increase in HDL cholesterol
*adiP↓,
*HDL↑,
*CRP↓, reduction was documented in inflammatory markers, including serum high-sensitivity C-reactive protein, soluble vascular adhesion molecule-1, and plasma IL-1β
*IL1β↓,
*Risk↓, lower Parkinson disease risk was associated with the highest quintile of anthocyanin (RR: 0.76) and berry (RR: 0.77) intake
*Risk↓, Nurse's Health Study, greater intake of blueberries and strawberries was associated with slower rates of cognitive decline in older adults, with an estimated delay in decline of about 2.5 y
*cognitive↑, Cognitive performance in elderly adults improved after 12 wk of daily intake of blueberry (94) or Concord grape (95) juice.
*memory↑, Better task switching and reduced interference in memory was found in healthy older adults after 90 d of blueberry supplementation
*other↑, After 12 wk of blueberry consumption, greater brain activity was detected using magnetic resonance imaging in healthy older adults during a cognitive challenge.
*BOLD↑, Similarly, during a memory test, regional blood oxygen level-dependent activity detected by MRI (99) was enhanced in the subjects taking blueberry, but not in those taking placebo.
*NO↓, 50–200 mg/d bilberry showed a dose-dependent decrease in neurotoxic NO and malondialdehyde, combined with an increase in neuroprotective antioxidant capacity due to glutathione, vitamin C, superoxide dismutase, and glutathione peroxidase
*MDA↓,
*GSH↑,
*VitC↑,
*SOD↑,
*GPx↑,
*eff↓, The percentage loss of blueberry anthocyanins during −18°C storage was 12% after 10 mo of storage
*eff↓, Freeze-dried blueberry powder loses anthocyanins in a temperature-dependent manner with a half-life of 139, 39, and 12 d when stored at 25, 42, and 60°C, respectively
*eff↓, Blueberries are low in ascorbic acid and high in anthocyanins (187), and notably anthocyanins are readily degraded by ascorbic acid
*eff↝, Shelf-stable blueberry products like jam (196), juice (197), and extracts (198) can lose polyphenolic compounds when stored at ambient temperature whereas refrigeration mitigates losses.
*Risk↓, It can be safely stated that daily moderate intake (50 mg anthocyanins, one-third cup of blueberries) can mitigate the risk of diseases and conditions of major socioeconomic importance in the Western world.

5355- AL,    Mini-review: The health benefits and applications of allicin
- Review, Var, NA
*BioAv↑, another key property of allicin is its hydrophobicity, which allows it to be absorbed easily through the cell membrane without causing any physical or chemical damage to the phospholipid bilayer, thereby allowing its rapid metabolism to produce pharm
*cardioP↑, Allicin exhibits protective effects in multiple organ systems, including the brain, intestines, lungs, liver, kidneys, prostate, and heart.
*hepatoP↑,
*RenoP↑,
*Half-Life↝, half-life (t1/2)of allicin was 227 min–260 min. Because allicin is eliminated from the body by the respiratory tract, the concentration of allicin in lung tissue is significantly lower than that in the blood
*BioAv↓, We believe that the bioavailability of allicin is relatively low for the following reasons: At first, allicin is characterized by a distinctive garlic odor and chemical instability. It can be easily degraded under room temperature.
*neuroP↑, Neuroprotective activity
*cognitive↑, On the other hand, allicin improves cognitive deficits via Protein kinase R-like endoplasmic reticulum kinase (PERK)/Nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway and c-Jun N-terminal kinase (JNK) signaling pathways
*ROS↓, They found that allicin suppressed ROS generation and decreased lipid peroxidation in 6-hydroxydopamine (6-OHDA)-induced Pheochromocytoma 12 (PC12) cells
*lipid-P↓,
*DNArepair↑, Allicin not only directly protects DNA, but also indirectly protects DNA through antioxidant activity and regulation of oxidizing enzymes
*ChemoSen↑, Allicin combined with other chemotherapy drugs showed a better anti-cancer effect

2558- AL,    Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment
- Review, AD, NA
*AntiCan↑, Allicin has shown anticancer, antimicrobial, antioxidant properties and also serves as an efficient therapeutic agent against cardiovascular diseases
*antiOx↑,
*cardioP↑,
*neuroP↑, present review describes allicin as an antioxidant, and neuroprotective molecule
cognitive↑, that can ameliorate the cognitive abilities in case of neurodegenerative and neuropsychological disorders.
*ROS↓, As an antioxidant, allicin fights the reactive oxygen species (ROS) by downregulation of NOX (NADPH oxidizing) enzymes, it can directly interact to reduce the cellular levels of different types of ROS produced by a variety of peroxidases.
*NOX↓,
*TLR4↓, inhibition of TLR4/MyD88/NF-κB, P38 and JNK pathways.
*NF-kB↓,
*JNK↓,
*AntiAg↑, A low concentration of allicin (0.4 mM) can inhibit the platelet aggregation up to 90%, the impact is significantly higher than of similar concentration of aspirin.
*H2S↑, Allicin decomposes rapidly and undergoes a series of reactions with glutathione resulting in the production of hydrogen sulphide (H2S).
*BP↓, H2S is a gaseous signalling molecule involved in the regulation of blood pressure.
Telomerase↓, Allicin inhibits the activity of telomerase in a dose dependent manner subsequently inhibiting the proliferation in the cancer cells
*Insulin↑, Studies have shown a significant increase in the blood insulin levels after treatment with allicin
BioAv↝, optimum temperature for the activity of alliinase is 33 °C, it operates best at pH 6.5, the enzyme is sensitive to acids [42,43] (Figure 3), enteric-coated formulations of garlic supplements are therefore recommended
*GSH↑, It helps to lower the hyperglycaemic conditions and improves the glutathione and catalase biosynthesis [37,38]
*Catalase↑,

2645- AL,    Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway
- NA, AD, NA
*neuroP↑, Allicin, a garlic extract, has been demonstrated a protective role in AD model.

2656- AL,    Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics
- in-vitro, Park, PC12
*antiOx↑, Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-oxidative and anti-apoptotic activities in in vitro and in vivo studies.
*Apoptosis↓, allicin treatment significant increased cell viability, and decreased LDH release and apoptotic cell death after 6-OHDA exposure
*LDH↓,
ROS↓, Allicin also inhibited ROS generation
*lipid-P↓, reduced lipid peroxidation and preserved the endogenous antioxidant enzyme activities.
*mtDam↓, These protective effects were associated with suppressed mitochondrial dysfunction,
*MMP↓, as evidenced by decreased MMP collapse and cytochrome c release,
*Cyt‑c↓,
*ATP∅, preserved mitochondrial ATP synthesis,
*Ca+2↝, and the promotion of mitochondrial Ca(2+) buffering capacity
*neuroP↑, allicin treatment can exert protective effects against PD related neuronal injury through inhibiting oxidative stress and mitochondrial dysfunction with dynamic changes.

2657- AL,    Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases
- Review, CardioV, NA - Review, AD, NA
*Inflam↓, allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others).
*antiOx↑, improving the antioxidant system
*neuroP↑,
*cardioP↑,
*AntiTum↑,
*mtDam↑, Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes.
*HSP70/HSPA5↑, llicin improves mitochondrial function by enhancing the expression of HSP70 and decreasing RAAS activation
*NRF2↑,
*RAAS↓,
*cognitive↑, Allicin enhances the cognitive function of APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice by decreasing the expression levels of Aβ, oxidative stress, and improving mitochondrial function.
*SOD↑, positive effects on cognition in an AD mouse model by administrating a preventive dose of allicin. These effects might be mediated by an increase of SOD and reduction of ROS
*ROS↓,
*NRF2↑, Chronic treatment with allicin increased the expression of NRF2 and targeted downstream of NRF2, such as NADPH, quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (γ-GCS), in the hippocampus of aged mice
*ER Stress↓, protective effects of 16 weeks of allicin treatment in a rat model of endoplasmic reticulum stress-related cognitive deficits.
*neuroP↑, allicin was able to ameliorate depressive-like behaviors by decreasing neuroinflammation, oxidative stress iron aberrant accumulation,
*memory↑, allicin improved lead acetate-caused learning and memory deficits and decreased the ROS level
*TBARS↓, Oral administration of allicin was able to reduce thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and concurrently increased (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in a rat model of
*MPO↓,
*SOD↑,
*GSH↑,
*iNOS↓, decreasing the expression of iNOS and increased the phosphorylation of endothelial NOS (eNOS)
*p‑eNOS↑,
*HO-1↑, OSCs upregulate the endogenous antioxidant NRF2 and heme oxygenase-1 (HO-1)

2661- AL,    Allicin alleviates traumatic brain injury-induced neuroinflammation by enhancing PKC-δ-mediated mitophagy
- in-vivo, Nor, NA
*TNF-α↓, Allicin treatment reduced TNF-α, IL-1β, IL-6, ROS levels, and the expression of NLRP3 and TLR4 proteins in mice with CCI, while IL-4 and IL-10 levels remained unchanged.
*IL1β↓,
*IL6↓,
*ROS↓,
*NLRP3↓,
*TLR4↓,
*PKCδ↑, allicin increased PKC-δ expression and PLS3 phosphorylation in the CL-related mitophagy process in both the CCI and Bv2 cell stretch models.
neuroP↑, allicin reduces mitophagy-related neuroinflammation and further prevents neuronal injury in vitro.

2660- AL,    Allicin: A review of its important pharmacological activities
- Review, AD, NA - Review, Var, NA - Review, Park, NA - Review, Stroke, NA
*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

3270- ALA,    Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis
- Trial, AD, NA
*cognitive↑, led to a stabilization of cognitive functions in the study group
*other↝, In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate.
*neuroP↑, alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD
*IronCh↑, a-Lipoic acid chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione
*ROS↓,
*GSH↑,

3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, Alpha-lipoic acid (α-LA), a natural antioxidant
*memory↑, multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects
*neuroP↑, α-LA could be considered neuroprotective
*Inflam↓, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies.
*IronCh↑, α-LA leads to a marked downregulation in iron absorption and active iron reserve inside the neuron
*NRF2↑, α-LA induces the activity of the nuclear factor erythroid-2-related factor (Nrf2), a transcription factor.
*BBB↑, capable of penetrating the BBB
*GlucoseCon↑, Fig 2, α-LA mediated regulation of glucose uptake
*Ach↑, α-LA may show its action on the activity of the ChAT enzyme, which is an essential enzyme in acetylcholine metabolism
*ROS↓,
*p‑tau↓, decreased degree of tau phosphorylation following treatment with α-LA
*Aβ↓, α-LA possibly induce the solubilization of Aß plaques in the frontal cortex
*cognitive↑, cognitive reservation of α-LA served AD model was markedly upgraded in additional review
*Hif1a↑, α-LA treatment efficaciously induces the translocation and activity of hypoxia-inducible factor-1α (HIF-1α),
*Ca+2↓, research found that α-LA therapy remarkably declines Ca2+ concentration and calpain signaling
*GLUT3↑, inducing the downstream target genes expression, such as GLUT3, GLUT4, HO-1, and VEGF.
*GLUT4↑,
*HO-1↑,
*VEGF↑,
*PDKs↓, α-LA also ameliorates survival in mutant mice of Huntington's disease [150–151], possibly due to the inhibition of the activity of pyruvate dehydrogenase kinase
*PDH↑, α-LA administration enhances PDH expression in mitochondrial hepatocytes by inhibiting the pyruvate dehydrogenase kinase (PDK),
*VCAM-1↓, α-LA inhibits the expression of cell-cell adhesion molecule-1 and VCAM-1 in spinal cords and TNF-α induced neuronal endothelial cells injury
*GSH↑, α-LA may enhance glutathione production in old-aged models
*NRF2↑, activation of the Nrf2 signaling by α-LA
*hepatoP↑, α-LA also protected the liver against oxidative stress-mediated hepatotoxicity
*ChAT↑, α-LA in mice models may prevent neuronal injury possibly due to an increase in ChAT in the hippocampus of animal models

3284- ALA,    Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA
- vitro+vivo, Park, NA
*antiOx↑, naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD.
*IronCh↑,
*neuroP↑,
*ROS↓, decreasing the levels of intracellular reactive oxygen species and iron.
*Iron↓,
*BBB↑, ALA also provides neuroprotection against PD because it can penetrate the blood–brain barrier.
*motorD↑, ALA ameliorates motor behavior and prevents DA neuron loss in the SN of PD rat models.
*GSH↑, ALA Inhibits the Decrease in the Activity of SOD and GSH in the SN of a Rat Model of PD Induced by 6-OHDA

3438- ALA,    The Potent Antioxidant Alpha Lipoic Acid
- Review, NA, NA - Review, AD, NA
*antiOx↑, Both of alpha lipoic acid and its reduced form have been shown to possess anti-oxidant, cardiovascular, cognitive, anti-ageing, detoxifying, anti-inflammatory, anti-cancer, and neuroprotective pharmacological properties
*cardioP↑,
*cognitive↑, Alpha lipoic acid has the ability to decrease cognitive impairment and may be a successful therapy for Alzheimer’s disease and any disease related dementias
*AntiAge↑,
*Inflam↓,
*AntiCan↑,
*neuroP↑, ALA has neuroprotective effects in experimental brain injury caused by trauma and subarachnoid hemorrhage
*IronCh↑, Also, the ability of ALA to chelate metals can produce an antioxidant effect
*ROS↑, DHLA can exert a pro-oxidant effect of donating its electrons for the reduction of iron, which can then break down peroxide to the prooxidant hydroxyl radical via the Fenton reaction [10]. So, ALA and its reduced form DHLA, can promote antioxidant pr
*Weight↓, α-lipoic acid supplementation at a dose of 300 mg/day might help to could help to promote weight loss and fat mass reduction in healthy overweight/obese women following an energy-restricted balanced diet
*Ach↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*ROS↓, also scavenges reactive oxygen species, thereby increasing the concentration levels of reduced Glutathione (GSH).
*GSH↑,
*lipid-P↓, Alpha lipoic acid can scavenge lipid peroxidation products as hydroxynonenal and acrolein.
*memory↑, learning and memory in the passive avoidance test partially through its antioxidant activity.
*NRF2↑, α-LA treatment has been shown to increase Nrf2 nuclear localization
*ChAT↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*GlucoseCon↑,
*Acetyl-CoA↑,

3440- ALA,    Protective effects of alpha lipoic acid (ALA) are mediated by hormetic mechanisms
- Review, AD, NA
*ROS↓, Mechanisms involving low levels of ROS activate key cell signaling pathways.
*neuroP↑, neuroprotection, graphical abstract
*Aβ↓,
*cardioP?, capacity of ALA to prevent oxidative stress induced cardiac apoptosis using rat cardio-myoblast H9c2 cells

3441- ALA,    α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice
- in-vivo, AD, NA
*tau↓, α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research
*GlucoseCon↑, chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brain
*GLUT3↑,
*GLUT4↑,
*VEGF↑,
*HO-1↑,
*Glycolysis↑, LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1).
*HK1↑, Our results indicated that the activity of HK was significantly increased after 10 mg/kg LA treatment.
*PGC-1α↑,
*Hif1a↑, found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.
*neuroP↑,

3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, antioxidant potential and free radical scavenging activity.
*ROS↓,
*IronCh↑, Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
*cognitive↑, α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties.
*cardioP↓,
AntiCan↑,
*neuroP↑,
*Inflam↓, α-Lipoic acid can reduce inflammatory markers in patients with heart disease
*BioAv↓, bioavailability in its pure form is low (approximately 30%).
*AntiAge↑, As a dietary supplements α-lipoic acid has become a common ingredient in regular products like anti-aging supplements and multivitamin formulations
*Half-Life↓, it has a half-life (t1/2) of 30 min to 1 h.
*BioAv↝, It should be stored in a cool, dark, and dry environment, at 0 °C for short-term storage (few days to weeks) and at − 20 °C for long-term storage (few months to years).
other↝, Remarkably, neither α-lipoic acid nor dihydrolipoic acid can scavenge hydrogen peroxide, possibly the most abundant second messenger ROS, in the absence of enzymatic catalysis.
EGFR↓, α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor (EGFR) and the protein kinase B (PKB), also known as the Akt signaling, and induces apoptosis in human breast cancer cells
Akt↓,
ROS↓, α-Lipoic acid tramps the ROS followed by arrest in the G1 phase of the cell cycle and activates p27 (kip1)-dependent cell cycle arrest via changing of the ratio of the apoptotic-related protein Bax/Bcl-2
TumCCA↑,
p27↑,
PDH↑, α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production
Glycolysis↓,
ROS↑, HT-29 human colon cancer cells; It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form
*eff↑, Several studies have found that combining α-lipoic acid and omega-3 fatty acids has a synergistic effect in slowing functional and cognitive decline in Alzheimer’s disease
*memory↑, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function,
*motorD↑,
*GutMicro↑, modulates the gut microbiota without reducing the microbial diversity (

3444- ALA,    Alpha-Lipoic Acid Nootropic Review: Benefits, Use, Dosage & Side Effects
- Review, NA, NA
*BBB↑, ALA's ability to cross the blood-brain barrier and its dual solubility in both water and lipid environments position it as a promising compound in the realm of cognitive enhancement and neurological health
*cognitive↑,
*neuroP↑, Alpha-lipoic acid demonstrates robust neuroprotective and cognitive-enhancing effects through its potent antioxidant properties
*antiOx↑,

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
*antiOx↑, ability to maintain its antioxidant properties both in its oxidised and reduced form
*NRF2↑, Antioxidant action of ALA is mediated by two essential nuclear factors: nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) [5,6,7,8,9,10]
*NF-kB↓,
*IL1β↓, ALA-dependent down-regulation of IL-1β and IL-6 in neuronal cells.
*IL6↓,
neuroP↑, ALA was already indicated as a potential therapeutic agent in aging-associated neurodegenerative disorders

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
*ATP↑, Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells.
*MMP↑, MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells.
*ROS↓, ROS levels were significantly lower in both cell lines treated with ALA.
*GlucoseCon↑, benefits to diabetic neuropathy and impaired glucose uptake, and the regeneration of glutathione (GSH) and vitamins C and E
*GSH↑,
*neuroP↑, ALA seems to have a positive effect on neurodegenerative diseases such as AD
*cognitive↑, ALA improves cognitive performance and could be considered as a promising bioactive substance for AD by affecting multiple mechanisms such as:
*Ach↑, (1) impaired acetylcholine production;
*Inflam↓, (2) hydroxyl radical formation, ROS production, and neuroinflammation;
*Aβ↓, (3) impaired amyloid plaque formation;
OXPHOS↓, ALA has also been shown to restore the expression of OXPHOS complexes in HepG2 cells, ranging in a concentration between 0.5–2 mM

3551- ALA,    Alpha lipoic acid treatment in late middle age improves cognitive function: Proteomic analysis of the protective mechanisms in the hippocampus
- in-vivo, AD, NA
*cognitive↑, ALA improves cognitive function in ageing mice.
*Apoptosis↓, ALA downregulates apoptosis, and neuroinflammatory associated proteins in ageing mice.
*Inflam↓,
*antiOx↑, Alpha lipoic acid (ALA), a powerful antioxidant, has the potential to relieve age-related cognitive impairment and neurodegenerative disease.
*BioAv↝, Alpha lipoic acid (ALA) is a sulfur-containing and both water-soluble and lipid-soluble coenzyme involved in the energy metabolism of carbohydrates, proteins and lipids
*neuroP↑, neuroprotective action of alpha lipoic acid has been demonstrated in a number of cellular or animal models of Parkinson's disease (PD), AD and amyotrophic lateral sclerosis (ALS) due to its antioxidative and anti-inflammatory properties

3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c

3543- ALA,    The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease
- Study, AD, NA
*cognitive↑, Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR.
*antiOx↑, Alpha-lipoic acid (ALA) is a naturally occurring disulfide molecule with antioxidant and anti-inflammatory properties.
*Inflam↓,
*neuroP↑, ALA plays many different roles in pathogenic pathways of dementia, acting as a neuroprotective agent.
*Ach↑, It increases acetylcholine production, inhibits hydroxyl radical production, and increases the process of getting rid of reactive oxygen species.
*ROS↓,
*GlucoseCon↑, (ii) increased glucose uptake, supplying more acetyl-CoA for the production of Ach;
*lipid-P↓, (v) scavenging lipid peroxidation products;
*GSH↑, (vi) inducing enzymes of glutathione synthesis
*Acetyl-CoA↑,

3550- ALA,    Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?
- Review, AD, NA
*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*PGE2↓, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6
*COX2↓,
*iNOS↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*BioAv↓, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic
*Ach↑, α-LA increases the production of acetylcholine [30], inhibits the production of free radicals [31], and promotes the downregulation of inflammatory processes
*ROS↓,
*cognitive↑, Studies have shown that patients with mild AD who were treated with α-LA showed a slower progression of cognitive impairment
*neuroP↑, α-LA is classified as an ideal neuroprotective antioxidant because of its ability to cross the blood-brain barrier and its uniform uptake profile throughout the central and peripheral nervous systems
*BBB↑,
*Half-Life↓, α-LA presented a mean time to reach the maximum plasma concentration (tmax) of 15 minutes and a mean plasma half-life (t1/2) of 14 minutes
*BioAv↑, LA consumption is recommended 30 minutes before or 2 hours after food intake
*Casp3↓, α-LA had an effect on caspases-3 and -9, reducing the activity of these apoptosis-promoting molecules to basal levels
*Casp9↓,
*ChAT↑, α-LA increased the expression of M2 muscarinic receptors in the hippocampus and M1 and M2 in the amygdala, in addition to ChaT expression in both regions.
*cognitive↑, α-LA acts on these apoptotic signalling pathways, leading to improved cognitive function and attenuation of neurodegeneration.
*eff↑, Based on their results, the authors suggest that treatment with α-LA would be a successful neuroprotective option in AD, at least as an adjuvant to standard treatment with acetylcholinesterase inhibitors.
*cAMP↑, The increase of cAMP caused by α-LA inhibits the release of proinflammatory cytokines, such as IL-2, IFN-γ, and TNF-α.
*IL2↓,
*INF-γ↓,
*TNF-α↓,
*SIRT1↑, Protein expression encoded by SIRT1 showed higher levels after α-LA treatment, especially in liver cells.
*SOD↑, antioxidant enzymes (SOD and GSH-Px) and malondialdehyde (MDA) were analysed by ELISA after 24 h of MCAO, which showed that the enzymatic activities were recovered and MDA was reduced in the α-LA-treated groups i
*GPx↑,
*MDA↓,
*NRF2↑, The ratio of nucleus/cytoplasmic Nrf2 was higher in the α-LA group 40 mg/kg, indicating that the activation of this factor also occurred in a dose-dependent manner

3549- ALA,    Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
- Review, AD, NA
*Inflam↓, LA and ALA attenuate neuroinflammation by modulating inflammatory signaling.
*other↝, ratio of LA to ALA in typical Western diets is reportedly 8–10:1 or higher, which is rather higher than the ideal ratio of LA to ALA (1–2:1) required to reach the maximal conversion of ALA to its longer chain PUFAs
*other↝, LA and ALA are essential PUFAs that must be obtained from dietary intake because they cannot be synthesized de novo
*neuroP↑, several studies have also suggested that lower dietary intake of LA influences AA metabolism in brain and subsequently causes progressive neurodegenerative disorders
*BioAv↝, LA cannot be synthesized in the human body
*adiP↑, study suggested that LA-rich oil consumption leads to the high levels of adiponectin in the blood [114], which could stimulate mitochondrial function in the liver and skeletal muscles for energy thermogenesis
*BBB↑, Although LA can penetrate the BBB, most of the LA that enters the brain cannot be changed into AA [48,49], and 59 % of the LA that enters the brain is broken down by fatty acid β-oxidation
*Casp6↓, In neurons, LA and ALA attenuate the activation of cleaved caspase-3/-9, p-NF-Kb and the production of TNF-a, IL-6, IL-1b, and ROS by binding GPR40 and GPR120.
*Casp9↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*ROS↓,
*NO↓, LA reduces NO production and inducible nitric oxide synthases (iNOS) protein expression in BV-2 microglia
*iNOS↓,
*COX2↓, ALA increases antioxidant enzyme activities in the brain [182] and inhibits the activation of COX-2 in AD models
*JNK↓, ALA has also been shown to suppress the activation of c-Jun N-terminal kinases (JNKs) and p-NF-kB p65 (Ser536), which is involved in inflammatory signaling
*p‑NF-kB↓,
*Aβ↓, and to inhibit Aβ aggregation and neuronal cell necrosis
*BP↓, LA also improves blood pressure, blood triglyceride and cholesterol levels, and vascular inflammation
*memory↑, One study suggested that long-term intake of ALA enhances memory function by increasing hippocampal neuronal function through activation of cAMP response element-binding protein (CREB) [192], extracellular signal-regulated kinase (ERK), and Akt signa
*cAMP↑,
*ERK↑,
*Akt↑,
cognitive?, Furthermore, ALA administration inhibits Aβ induced neuroinflammation in the cortex and hippocampus and enhances cognitive function

3548- ALA,    How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease
- Review, AD, NA
*BBB↑, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements,
*other↑, Apolipoprotein E4 (ApoE4) allele carriers are at increased risk to develop AD compared with those carrying the ApoE3 or E2 alleles
*other↑, Our emerging, yet unpublished results, suggest that ALA dietary enrichment in ApoE4 compared with ApoE3 mice brain, restores part of the decreased lipids, and in particular cholesterol and phospholipids, and leads to DHA enrichment in brain blood ve
*DHA↑, We propose that, by conversion to DHA, ALA– the natural substrate in the DHA metabolic pathway– may produce the DHA beneficial effects on BBB and brain health.
*neuroP↑, It has also been shown that DHA confers long-term protection against ischemic brain damage through multiple mechanisms, including suppression of inflammatory responses, decrease in oxidative stress and stimulation of angiogenesis and neurogenesis
*ROS↓,
*other?, while AD pathology follows a long preclinical course, with DHA decrease being a hallmark of brain deterioration with aging [67].

3547- ALA,    Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration
- Review, AD, NA - Review, Park, NA
*memory↑, a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect
*neuroP↑,
*motorD↑, Improved motor dysfunction
*VitC↑, elevates the activities of antioxidants such as ascorbate (vitamin C), α-tocoferol (vitamin E) (Arivazhagan and Panneerselvam, 2000), glutathione (GSH)
*VitE↑,
*GSH↑,
*SOD↑, superoxide dismutase (SOD) activity (Arivazhagan et al., 2002; Cui et al., 2006; Militao et al., 2010), catalase (CAT) (Arivazhagan et al., 2002; Militao et al., 2010), glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*5HT↑, ↑levels of neurotransmitters (dopamine, serotonin and norepinephrine) in various brain regions
*lipid-P↓, ↓ level of lipid peroxidation,
*IronCh↑, ↓cerebral iron levels,
*AChE↓, ↓ AChE activity, ↓ inflammation
*Inflam↓,
*GlucoseCon↑, ↑brain glucose uptake; ↑ in the total GLUT3 and GLUT4 in the old mice;
*GLUT3↑,
*GLUT4↑,
NF-kB↓, authors showed that LA inhibited the stimulation of nuclear factor-κB (NF-κB)
*IGF-1↑, LA restored the parameters of total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Mahboob et al. (2016), analyzed the effects of LA in AlCl3- model of neurodegeneration,
*IL1β↓,
*TNF-α↓, Suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α) followed inhibition of cleaved caspase-3
*cognitive↑, demonstrating its capacity in ameliorating cognitive functions and enhancing cholinergic system functions
*ChAT↑, LA treatment increased the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) relative to AlCl3-treated group.
*HO-1↑, R-LA and S-LA also enhanced expression of genes related to anti-oxidative response such as heme oxygenase-1 (HO-1) and phase II detoxification enzymes such as NAD(P)H:Quinone Oxidoreductase 1 (NQO1).
*NQO1↑,

3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron, zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils

3544- ALA,    Alpha lipoic acid for dementia
- Review, AD, NA
*antiOx↑, ALA is a low molecular weight antioxidant, readily absorbed from the diet or an oral dose, and crosses the blood brain barrier
*BBB↑,
*VitC↑, DHLA regenerates through redox cycling other antioxidants like vitamin C and E and raises levels of intracellular glutathione, an important thiol antioxidant
*VitE↑,
*GSH↑,
*IronCh↑, ALA al- so chelates certain metals, forming stable complexes with copper, manganese and zinc (Sigel 1978)
*neuroP↑, ALA would seem an ideal candidate as an antioxidant agent in neurodegenerative diseases.
*NO↓, ALA also modulates nitric oxide levels in brain and neural tissue, which may have effects in neurodegeneration, learning, cognition, and aging (Gross 1995)
*cognitive↑, elderly patients with dementia were given ALA. Findings suggested a stabilization of cognitive functions in the study group,
*AntiAge↑,
*memory↑, ALA has gained considerable attention following studies demonstrating partial reversal of memory loss in aged rats.
*ROS↓, scavenging hy- droxyl or superoxide radicals (Suzuki 1991) and by scavenging per- oxyl radicals (

297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, ALA is capable of activating pyruvate dehydrogenase in tumor cells.
TumCG↓, ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells
ROS↑, ALA is able to generate ROS, which promote ALA-dependent cell death in lung cancer [75], breast cancer [76] and colon cancer
AMPK↑,
EGR4↓,
Half-Life↓, Data suggests that ALA has a short half-life and bioavailability (about 30%)
BioAv↝,
*GSH↑, Moreover, it is able to increase the glutathione levels inside the cells, that chelate and excrete a wide variety of toxins, especially toxic metals from the body
*IronCh↑, The existence of thiol groups in ALA is responsible for its metal chelating abilities [14,35].
*ROS↓, ALA exerts a direct impact in oxidative stress reduction
*antiOx↑, ALA is being referred as the universal antioxidant
*neuroP↑, ALA has neuroprotective effects on Aβ-mediated cytotoxicity
*Ach↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*lipid-P↓, ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products
*IL1β↓, ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells
*IL6↓,
TumCP↓, ALA inhibited cell proliferation, [18F]-FDG uptake and lactate formation and increased apoptosis in neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and in the breast cancer cell line SkBr3.
FDG↓,
Apoptosis↑,
AMPK↑, ALA suppressed thyroid cancer cell proliferation and growth through activation of AMPK and subsequent down-regulation of mTOR-S6 signaling pathway in BCPAP, HTH-83, CAL-62 and FTC-133 cells lines.
mTOR↓,
EGFR↓, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation
TumCI↓, ALA inhibited metastatic breast cancer cells migration and invasion, partly through ERK1/2 and AKT signaling
TumCMig↓,
*memory↑, Alzheimer’s Disease: ALA led to a marked improvement in learning and memory retention
*BioAv↑, Since ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
*BioAv↝, ALA were found to be considerably higher in adults with mean age greater than 75 years as compared to young adults between the ages of 18 and 45 years.
*other↓, ALA treatment has been recently studied by some clinical trials to explain its efficacy in preventing miscarriage
*other↝, 1800 mg of ALA or placebo were administrated orally every day, except during the period 2 days before to 4 days after administration of each dose of platinum to avoid potential interference with platinum’s antitumor effects
*Half-Life↓, Data shows a short half-life and bioavailability of about 30% of ALA due to mechanisms involving hepatic degradation, reduced ALA solubility as well as instability in the stomach.
*BioAv↑, ALA bioavailability is greatly reduced after food intake and it has been recommended that ALA should be admitted at least 2 h after eating or if taken before; meal should be taken at least 30 min after ALA administration
*ChAT↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*GlucoseCon↑,

5262- aLinA,    The Role of Alpha-Linolenic Acid and Other Polyunsaturated Fatty Acids in Mental Health: A Narrative Review
- Review, AD, NA
*neuroP↑, The evidence suggests that PUFAs are beneficial for mental health, brain function, and behavior. ALA, EPA, and DHA have very significant neuroprotective properties, particularly in inducing changes to the synaptic membrane and modulating brain cell s
*Risk↓, DHA is a primary component of neuronal membranes in regions critical to memory and cognition, such as the hippocampus and cortex, and low levels of DHA are associated with an increased risk of cognitive decline [16,22].
*cognitive↑, Omega-3 supplementation has shown promise in delaying cognitive decline and neurodegeneration, potentially due to its anti-inflammatory and antioxidative properties, as well as its role in neurogenesis and brain-derived neurotrophic factor (BDNF) enh
*Inflam↓,
*antiOx↑,
*BDNF↑,

4280- Api,    Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms
- Review, AD, NA - Review, Park, NA
*neuroP↑, Apigenin, a flavonoid found in various herbs and plants, has garnered significant attention for its neuroprotective properties
*antiOx↑, shown to possess potent antioxidant activity, which is thought to play a crucial role in its neuroprotective effects
*ROS↓, Apigenin has been demonstrated to scavenge ROS, thereby reducing oxidative stress and mitigating the damage to neurons
*Inflam↓, apigenin has been found to possess anti-inflammatory properties.
*TNF-α↓, inhibit the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, which are elevated in neurodegenerative diseases
*IL1β↓,
*PI3K↑, apigenin has been shown to activate the PI3K/Akt signaling pathway, which is involved in promoting neuronal survival and preventing apoptosis.
*Akt↑,
*BBB↑, Apigenin has additional neuroprotective properties due to its ability to cross the BBB and enter the brain
*NRF2↑, figure 1
*SOD↑, pigenin has also been shown to activate various antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)
*GPx↑,
*MAPK↓, Apigenin inhibits the MAPK signalling system, which significantly reduces oxidative stress-induced damage in the brain
*Catalase↑, , including SOD, catalase, GPx and heme oxygenase-1 (HO-1) [37].
*HO-1↑,
*COX2↓, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*PGE2↓,
*PPARγ↑, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*TLR4↓,
*GSK‐3β↓, Apigenin can inhibit the activity of GSK-3β,
*Aβ↓, Inhibiting GSK-3 can reduce Aβ production and prevent neurofibrillary disorders.
*NLRP3↓, Apigenin suppresses nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation by upregulating PPAR-γ
*BDNF↑, Apigenin causes upregulation of BDNF and TrkB expression in several animal models
*TrkB↑,
*GABA↑, Apigenin enhances GABAergic signaling by increasing the frequency of chloride channel opening, leading to increased inhibitory neurotransmission
*AChE↓, It blocks acetylcholinesterase and increases acetylcholine availability.
*Ach↑,
*5HT↑, Apigenin has been shown to increase 5-HT levels, decrease 5-HT turnover, and prevent dopamine changes.
*cognitive↑, Apigenin increases the availability of acetylcholine in the synapse after inhibiting AChE, thereby enhancing cholinergic neurotransmission and improving cognitive function and memory
*MAOA↓, apigenin acts as a monoamine oxidase (MAO) inhibitor and MAO inhibitors increase the levels of monoamines in the brain

1999- Api,  doxoR,    Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation
- in-vitro, Nor, NRK52E - in-vitro, Nor, MPC5 - in-vitro, BC, 4T1 - in-vivo, NA, NA
neuroP↑, APG has a protective role against DOX-induced nephrotoxicity
ChemoSen∅, without weakening DOX cytotoxicity in malignant tumors.
RenoP↑, potential protective agent against renal injury. attenuate renal toxicity in cancer patients treated with DOX.
selectivity↑, APG maintained the cytotoxicity of DOX to tumor cells but not to renal cells. APG alone exhibited a prominent cytotoxic effect on 4T1 cells (Fig. 9E), but not on normal renal cells, at the same concentration
chemoP↑, Furthermore, APG revealed a dose-dependent improvement in normal renal cells against DOX-induced injury (Fig. 9E), with an exacerbation observed in 4T1 cells
ROS↑, Our in vivo study revealed that DOX caused a severe reduction in SOD activity and GSH levels, accompanied by an increase in MDA, leading to the overproduction of ROS and induction of oxidative injuries.
*ROS∅, Noteworthily, these changes were suppressed by APG(meaning on normal cells), consistent with several previous reports
*antiOx↑, APG has a similar antioxidative role as NAC and scavenges DOX-induced oxygen radicals and inhibits apoptosis significantly, implying that antioxidative stress is one of the main mechanisms through which APG protects renal tubular cells against DOX cy
*toxicity↓, We confirmed that APG mitigated the toxicity of DOX on normal renal cells by inhibiting oxidative stress, inflammation, and apoptosis.

2636- Api,    Apigenin unveiled: an encyclopedic review of its preclinical and clinical insights
- Review, NA, NA
*AntiCan↑, clinical studies are beginning to affirm apigenin's therapeutic benefits, showing positive effects in treating cancer, cardiovascular diseases, diabetes, neurodegenerative disorders, and inflammatory conditions.
*cardioP↑, The findings suggest that apigenin could serve as an effective therapeutic agent to reduce cardiotoxicity caused by Doxorubicin
*neuroP↑,
*Inflam↓,
*antiOx↑, apigenin (5,7,4′-trihydroxyflavone) is a flavonoid that chelates redox-active metals and has antioxidant properties
*hepatoP↑, Overall, the results indicate that apigenin alleviated liver injury by reducing inflammation and oxidative stress via suppression of the non-canonical NF-κB pathway
ChemoSen↑, Apigenin increases the cytotoxicity of sorafenib

3886- Api,    Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease
- in-vitro, AD, NA
*Inflam↓, apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells.
*neuroP↑, demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model.
*NO↓,
*Apoptosis↓, Apigenin reduces apoptosis in sporadic AD and control neurons

3885- Api,    Anti-Inflammatory and Neuroprotective Effect of Apigenin: Studies in the GFAP-IL6 Mouse Model of Chronic Neuroinflammation
- in-vivo, AD, NA
*memory↑, Apigenin also improved spatial reference working memory in the GFAP-IL6 mice.
*Inflam↓, Apigenin is a potent anti-inflammatory and neuroprotective drug and can be potentially used for neurodegenerative diseases such as AD.
*neuroP↑,

3884- Api,    Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model
- in-vivo, AD, NA
*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.

3666- ART/DHA,    Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling
- NA, AD, NA
*Inflam↓, Artemisinin has potent anti-inflammatory and immune activities.
*neuroP↑, Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway.
*TLR4↓,
*NF-kB↓,
*memory↑, reversing spatial learning and memory deficits.
*ROS↓, Artemisinin Decreased the Production of ROS and iNOS in BV2 Cells
*iNOS↓,
*COX2↓, Artemisinin treatment decreased the expression of COX2 and iNOS
*cognitive↑, Artemisinin Improved the Cognitive Impairment of AD Model Mice

3667- ART/DHA,    Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in microglia
- Review, Sepsis, NA
*cognitive↑, artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests
*neuroP↑, attenuated neuronal damage and microglial activation in the hippocampus.
*TNF-α↓, artemisinin (40 μΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6)
*IL6↓,
*NF-kB↓, artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway;
*AMPK↑,
*ROS↓, artemisinin protects neuronal HT-22 cells from oxidative injury by activating the Akt pathway
*Akt↑,
*MCP1↓, artemisinin reversed the LPS-induced increases in the chemokines MCP-1 and MIP-2
*MIP2↓,
*TGF-β↑, Artemisinin also significantly increased the mRNA and protein expression of TGF-β
*Inflam↓, The AMPKα1 pathway is involved in the anti-inflammatory effect of artemisinin

4278- ART/DHA,    Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway
- in-vivo, NA, NA
*IL6↓, ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression.
*Casp3↓,
*Casp9↓,
*BDNF↑,
*ERK↑,
*NRF2↑,
*HO-1↑,
*neuroP↑, ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.
*antiOx↑,
*Inflam↓,

3675- Ash,    Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)
*memory↑, widely in Ayurvedic medicine as a nerve tonic and memory enhancer.
*neuroP↑, neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.
*Aβ↓, Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ)
*LDH↓, Ashwagandha treatment showed protective effects against the cytotoxicity as the levels of LDH leakage in Ashwagandha plus β-amyloid treated cultures were comparable with controls
*PPARγ↑, decreased PPARγ protein levels in β-amyloid treated and its reversal by Ashwagandha in SK-N-MC neuronal cells.
*cognitive↑, traditional medicine for cognitive and other HIV associated neurodegenerative disorders.

3670- Ash,    Neurodegenerative diseases and Withania somnifera (L.): An update
- Review, AD, NA - Review, Park, NA
*Apoptosis↓, protective effects of Ashwagandha were accomplished by restoring mitochondrial and endothelial function, mitigation of apoptosis, inflammation and oxidative stress mechanisms.
*Inflam↓,
*ROS↓,
*neuroP↑, uggest the use of Withania somnifera (L.) against neurodegenerative disease

3674- Ash,    Ashwagandha in brain disorders: A review of recent developments
- Review, NA, NA
*neuroP↑, neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide neuroprotective phytoconstituents of Ashwagandha are sitoindos

3687- Ash,    Role of Withaferin A and Its Derivatives in the Management of Alzheimer’s Disease: Recent Trends and Future Perspectives
- Review, AD, NA
*Aβ↓, neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents.
*tau↓,
*HSPs↝, WA inhibited Hsp90 [127] and induced Hsp 27 and Hsp70 expressions
*antiOx↑,
*ROS↓,
*Inflam↓,
*neuroP↑, confirming WA’s neuroprotective potency against AD.
*cognitive↑, In an AD model, cognitive defects induced by ibotenic acid that was significantly reversed by WA isolated from Ashwagandha root
*NF-kB↓, inhibited nuclear factor NF-κB activation
*HO-1↑, WA also increased the neuro-protective protein heme oxygenase-1, which is beneficial to AD prevention
*memory↑, WA additionally enhances memory [133], prevents Aβ production, reconstructs synapses, and regenerates axons
*AChE↓, WA Inhibits AChE and BuChE Activities
*BChE↓,
*ChAT↑, WA has an important role in AD by reversing the reduction in cholinergic markers such as choline acetyltransferase (ChAT) and acetylcholine
*Ach↑, WA increased the level of ACh, the amount of choline acetyltransferase (ChAT)

3688- Ash,    Withaferin A Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine Associated Neurological Dysfunctions
- NA, AD, SH-SY5Y
*Aβ↓, WA reduces secreted Aβ and induced neurotoxicity in amyloid precursor protein (APP)-plasmid transfected SH-SY5Y cells (SH-APP)
*neuroP↑, WA Reverses/Decreases coc Induced Neurotoxicity

3672- Ash,    Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa
- Review, NA, NA
*cardioP↑, W. somnifera extracts are confirmed to have a significant cardioprotection effect based on the myocardial and antioxidant histopathological evaluations
*antiOx↑,
*ROS↓, reduced oxidative stress,
*neuroP↑, most reported neuroprotective mechanisms of W. somnifera extracts against several neurodegenerative diseases include the restoration of mitochondrial function concurrent with the mitigations of oxidative stress, inflammation, and apoptosis
*Inflam↓,
*Apoptosis↓,

3159- Ash,    Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model
- in-vitro, Park, SH-SY5Y
*neuroP↑, Neuroprotective effects of Withania somnifera
*Inflam↓, including inflammation and oxidative stress reduction, memory and cognitive function improvement.
*ROS↓,
*cognitive↑,
*memory↑,
*GPx↑, significantly increased glutathione peroxidase activity
*Prx↓, KSM-66, had peroxiredoxin-1 and VGF levels significantly lower than the untreated control
*ATP↑, rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels.
*Vim↓, Pre-treatment with KSM-66 decreased level of vimentin
*mtDam↓, KSM-66 attenuates 6-OHDA-induced mitochondrial dysfunction in SH-SY5Y cells

3161- Ash,    Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage
- in-vivo, Stroke, NA
*neuroP↑, Withaferin A (WFA), a natural compound, exhibits a positive effect on a number of neurological diseases
*MDA↓, WFA markedly decreased the level of malondialdehyde, an oxidative stress marker,
*ROS↓,
*SOD↑, and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase
*GPx↑,
*NRF2↑, results demonstrated that WFA activated the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis, promoted translocation of Nrf2 from the cytoplasm to nucleus, and increased HO-1 expression.
*HO-1↑, WFA induces HO-1 expression to attenuate oxidative damage in vitro

3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117


Showing Research Papers: 1 to 50 of 514
Page 1 of 11 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 514

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   HO-1↑, 1,   NQO1↑, 1,   NRF2↑, 1,   OXPHOS↓, 2,   ROS↓, 3,   ROS↑, 5,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   AMPK↑, 3,   FASN↓, 1,   FDG↓, 1,   Glycolysis↓, 1,   LDH↓, 1,   PDH↑, 2,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   Bcl-2↓, 2,   Casp12↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   Fas↑, 1,   JNK↑, 1,   p27↑, 1,   p38↑, 1,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 1,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   P53↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CycB/CCNB1↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   FOXO3↑, 1,   mTOR↓, 2,   NOTCH3↓, 1,   PI3K↓, 1,   STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

p‑FAK↓, 1,   N-cadherin↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 2,   EGR4↓, 1,   Hif1a↓, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL6↓, 1,   IL8↓, 1,   NF-kB↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 2,   ChemoSen↑, 1,   ChemoSen∅, 1,   eff↑, 2,   Half-Life↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   IL6↓, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   chemoP↑, 2,   cognitive?, 1,   cognitive↑, 1,   neuroP↑, 4,   RenoP↑, 1,  
Total Targets: 73

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 27,   Catalase↑, 4,   GPx↑, 8,   GSH↑, 15,   GSTs↑, 1,   H2O2∅, 1,   HDL↑, 1,   HK1↑, 1,   HO-1↑, 8,   Iron↓, 1,   Keap1↓, 1,   lipid-P↓, 8,   MDA↓, 4,   MPO↓, 2,   NQO1↑, 1,   NRF2↑, 12,   Prx↓, 1,   ROS↓, 31,   ROS↑, 1,   ROS∅, 1,   SOD↑, 10,   TBARS↓, 2,   VitC↑, 4,   VitE↑, 3,  

Metal & Cofactor Biology ⓘ

IronCh↑, 10,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 3,   ATP∅, 1,   Insulin↑, 1,   MMP↓, 1,   MMP↑, 1,   mtDam↓, 2,   mtDam↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↑, 2,   adiP↓, 1,   adiP↑, 1,   ALAT↓, 1,   AMPK↑, 3,   cAMP↑, 2,   p‑CREB↑, 1,   DHA↑, 1,   glucose↓, 1,   GlucoseCon↑, 8,   Glycolysis↑, 1,   H2S↑, 2,   LDH↓, 5,   LDL↓, 1,   PDH↑, 1,   PDKs↓, 1,   PPARγ↑, 2,   p‑PPARγ↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 4,   Apoptosis↓, 5,   Casp3↓, 2,   Casp6↓, 1,   Casp9↓, 3,   Cyt‑c↓, 1,   iNOS↓, 5,   JNK↓, 2,   MAPK↓, 1,   MAPK↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 9,   other?, 1,   other↓, 1,   other↑, 4,   other⇅, 1,   other↝, 5,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   HSP70/HSPA5↑, 1,   HSPs↝, 1,  

DNA Damage & Repair ⓘ

DNArepair↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 3,   p‑ERK↑, 1,   GSK‐3β↓, 1,   IGF-1↑, 1,   PI3K↓, 1,   PI3K↑, 2,   PTEN↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↓, 1,   Ca+2↝, 1,   MMP9↓, 1,   PKCδ↑, 2,   TGF-β↑, 1,   VCAM-1↓, 4,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

p‑eNOS↑, 1,   Hif1a↑, 2,   NO↓, 5,   VEGF↑, 2,  

Barriers & Transport ⓘ

BBB↑, 10,   GLUT3↑, 3,   GLUT4↑, 4,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CRP↓, 1,   ICAM-1↓, 1,   IL18↓, 1,   IL1β↓, 9,   IL2↓, 1,   IL6↓, 9,   IL8↓, 1,   INF-γ↓, 1,   Inflam↓, 27,   MCP1↓, 1,   MIP2↓, 1,   NF-kB↓, 8,   p‑NF-kB↓, 1,   PGE2↓, 3,   TLR4↓, 4,   TNF-α↓, 9,  

Cellular Microenvironment ⓘ

NOX↓, 1,  

Synaptic & Neurotransmission ⓘ

5HT↑, 3,   AChE↓, 3,   BChE↓, 1,   BDNF↑, 4,   ChAT↑, 7,   GABA↑, 1,   MAOA↓, 1,   tau↓, 2,   p‑tau↓, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 10,   BACE↓, 1,   NLRP3↓, 2,  

Hormonal & Nuclear Receptors ⓘ

RAAS↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 4,   BioAv↝, 8,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↓, 3,   eff↑, 4,   eff↝, 1,   Half-Life↓, 4,   Half-Life↑, 1,   Half-Life↝, 4,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BP↓, 3,   BP↝, 1,   creat↓, 1,   CRP↓, 1,   GutMicro↑, 3,   IL6↓, 9,   LDH↓, 5,  

Functional Outcomes ⓘ

AntiAge↑, 3,   AntiCan↑, 3,   AntiTum↑, 1,   BOLD↑, 1,   cardioP?, 1,   cardioP↓, 1,   cardioP↑, 9,   chemoPv↑, 1,   cognitive↑, 28,   hepatoP↑, 4,   memory↑, 18,   Mood↑, 1,   motorD↑, 3,   neuroP↑, 48,   RenoP↑, 1,   Risk↓, 4,   toxicity↓, 1,   Weight↓, 1,  
Total Targets: 167

Scientific Paper Hit Count for: neuroP, neuroprotective
21 Thymoquinone
20 Alpha-Lipoic-Acid
19 Resveratrol
18 Magnetic Fields
18 Quercetin
15 Silymarin (Milk Thistle) silibinin
15 Urolithin
14 Chlorogenic acid
13 Hydrogen Gas
12 Curcumin
12 Rosmarinic acid
11 Baicalein
11 Lycopene
10 Ashwagandha(Withaferin A)
10 Carvacrol
9 Berberine
9 Bacopa monnieri
9 Ferulic acid
9 Honokiol
8 Moringa oleifera
8 Sulforaphane (mainly Broccoli)
7 Allicin (mainly Garlic)
7 Piperine
7 Huperzine A/Huperzia serrata
7 Taurine
6 Apigenin (mainly Parsley)
6 Selenium NanoParticles
6 Chrysin
6 EGCG (Epigallocatechin Gallate)
6 Fisetin
6 Ginseng
6 Mushroom Lion’s Mane
6 Phenylbutyrate
6 Silicic Acid
5 Astaxanthin
5 Vitamin C (Ascorbic Acid)
5 Capsaicin
5 Crocetin
5 Luteolin
5 Piperlongumine
5 Shankhpushpi
5 Shikonin
5 Vitamin E
5 Vitamin B5,Pantothenic Acid
4 Boron
4 Boswellia (frankincense)
4 Carnosic acid
4 Carnosine
4 Propolis -bee glue
4 Folic Acid, Vit B9
4 Shilajit/Fulvic Acid
4 Magnetic Field Rotating
4 Pterostilbene
4 Vitamin B12
3 Anthocyanins
3 Artemisinin
3 Biochanin A
3 Betulinic acid
3 Vitamin B6,pyridoxine
3 Caffeic acid
3 Exercise
3 Celastrol
3 Coenzyme Q10
3 Cysteamine
3 diet Short Term Fasting
3 Methylene blue
3 Magnolol
3 Melatonin
3 nicotinamide adenine dinucleotide
3 Rutin
3 Selenite (Sodium)
3 Ursolic acid
2 Baicalin
2 beta-carotene(VitA)
2 borneol
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Thymol-Thymus vulgaris
2 Chlorophyllin
2 Choline
2 Calorie Restriction Mimetics
2 Spermidine
2 Metformin
2 Ellagic acid
2 Emodin
2 Ginkgo biloba
2 EMF
2 Naringin
2 Phosphatidylserine
2 Chemotherapy
2 Vitamin D3
2 Vitamin K2
1 alpha Linolenic acid
1 doxorubicin
1 Butyrate
1 Paclitaxel
1 chitosan
1 Cinnamon
1 Selenium
1 Hydroxycinnamic-acid
1 Aspirin -acetylsalicylic acid
1 Silver-NanoParticles
1 Dichloroacetate
1 Bortezomib
1 diet Methionine-Restricted Diet
1 diet FMD Fasting Mimicking Diet
1 MCToil
1 Methylsulfonylmethane
1 Psoralidin
1 Salvia officinalis
1 Aromatherapy
1 Sesame seeds and Oil
1 Anti-oxidants
1 Aflavin-3,3′-digallate
1 Vitamin A, Retinoic Acid
1 Vitamin B1/Thiamine
1 Vitamin B3,Niacin
1 Zinc
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#:1105  State#:%  Dir#:2
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