tau Cancer Research Results

tau, tau: Click to Expand ⟱
Source:
Type:
In healthy neurons, tau binds to and stabilizes microtubules, which are essential for maintaining cell structure and facilitating axonal transport.

In AD, tau becomes abnormally hyperphosphorylated. This excessive phosphorylation reduces its affinity for microtubules, leading to destabilization of the cytoskeletal structure.
-Abnormal phosphorylated tau (p-tau) can be detected in cerebrospinal fluid (CSF) and blood plasma.
-Imaging techniques like tau PET scans can visualize tau deposits in the brain.
Natural Products targeting tau
-Curcumin                via GSK-3β inhibition
-Resveratrol             Activates SIRT1
-EGCG                    inhibits Tau, but BBB penetration is questionable
Scientific Papers found: Click to Expand⟱
6461- 1,8-Cin,    1,8-cineole (eucalyptol): A versatile phytochemical with therapeutic applications across multiple diseases
- Review, AD, NA - Review, Var, NA
*Inflam↓, long history of use in traditional medicine and exhibits an array of biological properties, including anti-inflammatory, antioxidant, antimicrobial, bronchodilatory, analgesic, and pro-apoptotic effects.
*antiOx↑,
*neuroP↑, recent studies have highlighted the neuroprotective, analgesic, and pro-apoptotic properties of 1,8-cineole, underscoring its potential beneficial role in a broad spectrum of conditions such as Alzheimer’s disease, neuropathic pain, and cancer
*BioAv↑, Marked by a logP value of 2.74, 1,8-cineole strikes an optimal equilibrium between solubility and permeability, hinting at its favorable potential for oral bioavailability
*Half-Life↝, In rabbits, oral administration of 200 mg/kg has led to rapid attainment of peak plasma concentration within 1 h, indicating efficient absorption
*toxicity↓, compound’s toxicity profile, the oral acute LD50 value in rats is documented at 2480 mg/kg body weight
*PGE2↓, 1,8-cineole decreased the release of prostaglandin E2 and leukotriene B4 (LTB4) from peripheral blood mononuclear cells in asthmatic patients, and reduced TNF-α, IL-1β, LTB4, and thromboxane B2 in lipopolysaccharide (LPS)-stimulated peripheral blood
*TNF-α↓,
*IL1β↓,
*NO↓, 1,8-cineole hindered LPS-induced nitric oxide (NO) production in mouse macrophage cell lines
*NF-kB↓, inhibition of nuclear translocation of NF-κB p65 and PPARγ, leading to the suppression of immune response genes.
*PPARγ↓,
COX2↓, ,8-cineole has been found to impede UVB-induced COX-2 protein and mRNA production in HaCaT cells
*ROS↓, 1,8-cineole’s antioxidant properties play a crucial role in its therapeutic potential, as it is effective in neutralizing reactive oxygen species (ROS)
*SOD↑, 1,8-cineole treatment enhanced antioxidant enzymes activities, such as superoxide dismutase (SOD) and catalase (CAT), increased total antioxidant capacity, and decreased ROS and malondialdehyde (MDA)
*Catalase↑,
*TAC↑,
*MDA↓,
*lipid-P↓, 1,8-cineole has demonstrated the ability to inhibit LP
*NRF2↑, The antioxidant activity of 1,8-cineole is mediated, in part, by activating the Nrf2/Keap1 system
*HO-1↑, increased expression of phase II detoxifying enzymes and antioxidant proteins, such as heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 (NOQ1)
*NADPH↑,
*GPx↑, 1,8-cineole treatment has been shown to enhance the activities of antioxidant enzymes, such as SOD, GPx, and CAT,
*AntiBio↑, Antibacterial properties: activity, synergy with antibiotics, and impact on biofilm formation and cell morphology
*eff↑, Although 1,8-cineole exhibited weaker bactericidal activity than commonly used antibiotics such as gentamicin and amoxicillin (AMX)/clavulanic acid, it significantly reduced the minimum inhibitory concentration of antibiotics when used in combination
*AntiFungal↑, Antifungal properties: inhibition of fungal growth and disruption of biofilm formation
*AntiViral↑, Antiviral properties: inhibition of viral replication and enhancement of antiviral responses
*TRPA1↑, 1,8-cineole could activate TRPA1 channels in the dorsal root ganglia (DRG),
eff↑, when combined with simvastatin, increased G0/G1 cell cycle arrest and sensitized cells to apoptosis
TumCCA↑, 1,8-cineole induced G0/G1 arrest and senescence in HepG2 cells through oxidative stress and various signaling pathways such as MAPK, AMPK, and Akt/mTOR
ROS↑,
MAPK↝,
mTOR↝,
Apoptosis↑, HCT116 and RKO human colon cancer cell lines, 1,8-cineole selectively promoted apoptosis rather than necrosis
survivin↓, This process was linked to survivin and Akt inactivation, along with p38 activation.
Akt↓,
p38↑,
cl‑PARP↑, triggered subsequent cleavage of PARP and caspase-3, resulting in apoptosis.
cl‑Casp3⇅,
P53↑, increasing p53 expression, as well as the expression of apoptotic proteins (Bax/Bcl-2, Cyt-c, caspase-9, and caspase-3)
BAX↑,
Cyt‑c↑,
Casp9↑,
Dose↝, efficacious concentrations of 1,8-cineole reported for inhibiting in vitro cancer cell proliferation range from micromolar [135], [136] to millimolar (mM)
*Aβ↓, 1,8-cineole in rat PC12 cells (pheochromocytoma cells) demonstrated effective mitigation of the Aβ induced cytotoxicity and oxidative stress
*tau↓, 1,8-cineole has shown the ability to modulate tau phosphorylation by suppressing GSK-3β activity and to reduce Aβ production by inhibiting beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), both in vitro and in vivo
*GSK‐3β↓,
*BACE↓,
*cardioP↑, 1,8-cineole enhanced cell viability, inhibited cardiac hypertrophy, attenuated cardiac remodeling, improved cardiac function, and decreased the concentrations of atrial natriuretic peptide and brain natriuretic peptide in rat hearts
MFN2↑, 1,8-cineole was also found to inhibit the activation of dynamin-related protein 1 and promote mitochondrial fusion by increasing MFN2.

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

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↑,

3819- Aroma,    Aromatherapy improves cognitive dysfunction in senescence-accelerated mouse prone 8 by reducing the level of amyloid beta and tau phosphorylation
- Human, AD, NA - in-vitro, AD, NA
*cognitive↑, benefits of aromatherapy on the cognitive function of patients with AD utilizing various aromatic essential oils
*Dose↝, The mice were exposed to a mixture of lemon and rosemary oil at nighttime as well as to a mixture of lavender and orange oil in the daytime for 2 months.
*Aβ↓, brain levels of Aβ and abnormally phosphorylated tau were considerably lower in the aromatherapy group, while the levels of BDNF were marginally higher.
*tau↓,
*BDNF↑,
*motorD↑, fig 1

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)

4303- Ash,    Ashwagandha (Withania somnifera)—Current Research on the Health-Promoting Activities: A Narrative Review
- Review, AD, NA
*neuroP↑, neuroprotective, sedative and adaptogenic effects and effects on sleep.
*Sleep↑,
*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties
*cardioP↑,
*cognitive↑, Significant improvements in cognitive function were observed as a result of the inhibition of amyloid β-42, and a reduction in pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and MCP-1, nitric oxide, and lipid peroxidation was also observed.
*Aβ↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*MCP1↓,
*lipid-P↓,
*tau↓, reducing β-amyloid aggregation and inhibiting τ protein accumulation.
*ROS↓, withaferin A is responsible for inhibiting oxidative and pro-inflammatory chemicals and regulating heat shock proteins (HSPs), the expression of which increases when cells are exposed to stressors.
*BBB↑, ability of withanolide A to penetrate the blood-brain barrier (BBB) was demonstrated.
*AChE↓, potentially inhibiting acetylcholinesterase activity, which may have benefits in the treatment of canine cognitive dysfunction and Alzheimer’s disease
*GSH↑, increased glutathione concentration, increased glutathione S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase activities,
*GSTs↑,
*GSR↑,
*GPx↑,
*SOD↑,
*Catalase↑,
ChemoSen↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin
*Strength↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin

4305- Ba,    Study on the Molecular Mechanism of Baicalin Phosphorylation of Tau Protein Content in a Cell Model of Intervention Cognitive Impairment
- in-vitro, NA, SH-SY5Y
*cognitive↑, In cell experiments, baicalein presented a positive impact on mild cognitive impairment by elevating P-AKT1 and P-GSK-3β levels while reducing the overall amount of P-tau.
*p‑Akt↑,
*p‑GSK‐3β↑,
*p‑tau↓,
*neuroP↑, baicalein demonstrates a neuroprotective by modulating pathways such as the NF-κB/MAPK signaling pathway and the AMPK/Nrf2 pathway.
*NF-kB↓,
*AMPK↑,
*NRF2↑,

4304- Ba,    Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation
- in-vitro, AD, NA
*tau↓, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action
*Dose↝, 85% at 500 μM of Baicalein and 75% at 100 μM Baicalein
*BioAv↓, the potency of Baicalein to be a therapeutic is hampered by its poor water solubility and low bioavailability.

3682- BBR,    Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer’s Disease
- in-vitro, AD, NA
*cognitive↑, results showed that BBR ameliorated cognitive deficits in 3×Tg AD mice, reduced the Aβ accumulation, inhibited the apoptosis of neurons
*Aβ↓,
*Apoptosis↓,
*CD31↑, promoted the formation of microvessels in the mouse brain by enhancing brain CD31, VEGF, N-cadherin, Ang-1.
*VEGF↑,
*N-cadherin↑,
*angioG↑,
*neuroP↑, berberine is effective to 3×Tg AD mice, has a neuroprotective effect,
*p‑tau↓, lowering Aβ levels, inhibiting the phosphorylation of Tau protein, anti-oxidation, inhibiting the activity of AchE and MAO, and regulating lipids, hypoglycemic.
*antiOx↑,
*AChE↓,
*MAOB↓,
*lipid-P↓,

3684- BBR,    Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies
- Review, AD, NA
*Inflam↓, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.
*antiOx↓,
*AChE↓,
*BChE↓, berberine exerts inhibitory effects on the four key enzymes in the pathogenesis of AD: acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A, and monoamine oxidase B
*MAOA↓,
*MAOB↓,
*lipid-P↓, Fig3
*GSH↑,
*ROS↓,
*APP↓,
*BACE↓,
*p‑tau↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*MAPK↓,
*PI3K↓,
*Akt↓,
*neuroP↑, neuroprotective effects of berberine have been extensively studied
*memory↑, berberine displayed significant effects in preventing memory impairment in these mechanistically different animal models, suggesting an over-all improvement of memory function by berberine

4298- BBR,    Berberine mitigates cognitive decline in an Alzheimer’s Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
- in-vivo, AD, NA
*cognitive↑, Berberine could improve 3×Tg AD mice’s cognitive function
*p‑tau↓, Berberine could attenuate the hyperphosphorylation of tau
*GSK‐3β↓, attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A
*PP2A↑, inhibition of GSK3β or activation of PP2A attenuates tau hyperphosphorylation, thus, ameliorates cognitive impairment
*memory↑, Berberine-treated mice showed better performance in spatial learning and memory test
*Akt↑, Berberine decreases tau phosphorylation via activation of Akt and inhibition of GSK3β
*LC3II↑, both LC3-Ⅱ and Beclin-1 in the hippocampus of BBR-treated group were dramatically increased compared with the 3×Tg AD mice
*Beclin-1↑,

4299- BBR,    Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation
- in-vivo, AD, NA
*memory↑, BBR improved learning and memory in APP/PS1 mice.
*p‑tau↓, BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice.
*NF-kB↓, BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice.
*GSH↑, BBR-administration promoted the activity of glutathione (GSH) and inhibited lipid peroxidation in the hippocampus of AD mice.
*lipid-P↓,
*cognitive↑, BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB
*ROS↓, by retarding oxidative stress and neuro-inflammation.
*Inflam↓,

6515- BCP,  Xan,    Advancing Brain Health Naturally: β-Caryophyllene and Xanthohumol as Neuroprotective Agents
- Review, AD, NA
*neuroP↑, β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models.
*BioAv↝, advanced drug-delivery systems, including polymer- and lipid-based nano- and microscale carriers. Such advancements not only enhance the bioavailability and therapeutic potential of these phytochemicals
*CB2 / CNR2↑, selective agonist of cannabinoid type 2 receptors (CB2-R)
*Inflam↓, BCP demonstrates anti-inflammatory properties by suppressing key inflammatory mediators, including inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB),
*iNOS↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*COX1↓, and cyclooxygenases COX-1 and COX-2.
*COX2↓,
*PPARα↑, actions are partly mediated through activation of peroxisome proliferator-activated receptors, particularly PPAR-α and PPAR-γ.
*PPARγ↑,
*ROS↓, decreased the generation of reactive oxygen species (ROS)
*tau↓, XAN has been shown to directly inhibit the fibrillization tau protein and disaggregate existing fibrils, effectively reducing tau-induced apoptosis in cellular models of AD
*NRF2↑, XAN has been consistently shown to activate the Nrf2/HO-1 pathway, enhancing antioxidant defenses and reducing reactive oxygen species (ROS) levels
*HO-1↑,
*AChE↓, XAN: its ability to inhibit cholinesterases (AChE and BChE) supports its potential for symptomatic treatment of AD,
*BChE↓,
*BioAv↓, XAN’s clinical translation is hindered by poor oral bioavailability and limited BBB penetration.

5483- BM,    The Role of Bacopa monnieri in Alzheimer’s Disease: Mechanisms and Potential Clinical Use—A Review
- Review, AD, NA
*cognitive↑, Bacopa monnieri, also known as brahmi, which has gained particular popularity for its cognitive-function-enhancing properties and neuroprotective effects.
*neuroP↑,
*PI3K↑, figure 3
*Akt↑,
*GSK‐3β↓,
*tau↓,
*ROS↓,
*MMP3↓,
*Casp1↓,
*Casp3↓,
*NF-kB↓,
*TNF-α↓,
*IL6↓,

5474- BM,    Pharmacological attributes of Bacopa monnieri extract: Current updates and clinical manifestation
*memory↑, Bacopa monnieri has been used for centuries in Ayurvedic medicine, alone or in combination with other herbs, as a memory and learning enhancer, sedative, and anti-epileptic.
*neuroP↑, Brahmi as a lead formulation for treating neurological disorders and exerting cognitive-enhancing effects.
*cognitive↑,
*hepatoP↑, figure 1
*antiOx↑,
*AntiDiabetic↑,
*fatigue↓,
*GSK‐3β↓, figure 3
*PI3K↑,
*Akt↑,
*tau↓,
*ROS↓, The neuroprotective properties of these bioactive components include reduction of ROS, neuroinflammation, aggregation inhibition of amyloid-β and improvement of cognitive and learning behavior.
*Inflam↓,

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
*neuroP↑, Caffeic acid (CA), a naturally occurring hydroxycinnamic acid, has emerged as a promising neuroprotective candidate due to its antioxidant, anti-inflammatory, and enzyme-inhibitory properties.
*antiOx↑,
*Inflam↓,
*AChE↓, CA modulates cholinergic activity by inhibiting AChE and BChE and exerting antioxidant and anti-amyloidogenic effects.
*BChE↓,
*cognitive↑, metabolic AD models have demonstrated improvements in cognitive function, reduction in oxidative stress, inflammation, and Aβ and tau pathologies following CA administration
*ROS↓,
*Aβ↓,
*tau↓,
eff↑, CA derivatives, including caffeic acid phenethyl ester and nitro-substituted analogs, exhibit improved pharmacokinetic and neuroprotective profiles.

3791- CA,    Caffeic Acid and Diseases—Mechanisms of Action
- Review, AD, NA
*memory↑, Feeding hyperinsulinemic rats with caffeic acid (30 mg/kg b.w./day) for 30 weeks significantly improved their memory and learning impairments caused by a high-fat diet
*cognitive↑, caffeic acid (100 mg/kg for two weeks) significantly improved learning deficits and increased cognitive function
*p‑tau↓, pretreatment with caffeic acid (10 μg/mL) decreased the level of phosphorylated tau protein
*ROS↓, Caffeic acid (100 mg/kg for two weeks) also suppressed oxidative stress, inflammation, NF-κB-p65 protein expression, and caspase-3 activity
*Inflam↓,
*NF-kB↓,
*Casp3↓,
*lipid-P↓, caffeic acid (50 mg/kg/day) improved cognitive functions and inhibited lipid peroxidation and nitric oxide formation in the brain
*AChE↓, Caffeic acid (12 μg/mL) inhibited acetylcholinesterase and butyrylcholinesterase activity in the brain of untreated rats in vitro
*BChE↓,
*GSK‐3β↓, improves cognitive functions, probably by inhibiting NF-κB and GSK3β signaling and acetylcholinesterase and butyrylcholinesterase activity (
*5LO↓, we consider the inhibitory effect of caffeic acid on 5-lipoxygenase as another factor in protecting the brain against damage
*BDNF↓, Caffeic acid also increased the expression of brain-derived neurotrophic factor (BDNF) in stressed mice; the effect was mediated by 5-lipoxygenase inhibition
VEGF↓, the primary way how caffeic acid affects hepatocellular carcinoma in vitro is inhibiting VEGF expression
HSP70/HSPA5↓, affeic acid (20 μM) also decreased the expression of mortalin(mitochondrial 70 kDa heat shock protein),

5860- CAP,    Beneficial Effects of Capsaicin in Disorders of the Central Nervous System
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, In Alzheimer’s disease, capsaicin reduces neurodegeneration and memory impairment.
*memory↑, dietary capsaicin (0.01% in a chow) improved memory in a mouse model of Alzheimer’s disease
*Pain↓, Additionally, this compound exerts pain-relieving effects in migraine and cluster headaches.
*TRPV1↑, capsaicin stimulates TRPV1 receptors
*Aβ↓, Alzheimer’s disease, that dietary capsaicin (0.01% in a chow) reduced beta-amyloid plaque formation and tau phosphorylation in different brain areas
*tau↓,
*cognitive↑, attenuated neurodegeneration and cognitive impairment
*Risk↓, In western regions of China, chili peppers are more often consumed and there is a smaller number of people with dementia than in other regions where dietary capsaicin intake is lower
*motorD↓, capsaicin reduced neurodegeneration and motor impairment in animal models of Parkinson’s disease
*ROS↓, this compound decreased the production of reactive oxygen species and proinflammatory cytokines (TNF-α and IL-β) by activated microglia
*TNF-α↓,
*IL1β↓,
*eff↑, Capsaicin exerts beneficial effects in stroke models not only by enhancing neuroprotection but also by influencing cerebral vasculature.
*Risk↓, Moreover, it was reported that dietary capsaicin (0.02% in a chow) delays the onset of stroke in stroke-prone rats with hypertension.

5854- CAP,    Pharmacological activity of capsaicin: Mechanisms and controversies (Review)
- Review, Var, NA - Review, AD, NA
Obesity↓, Capsaicin can also promote weight loss, making it potentially useful for treating obesity.
Half-Life↓, The clinical usefulness of capsaicin is limited by its short half-life.
antiOx↑, Capsaicin exerts analgesic, antioxidant, cardioprotective, anticancer and thermogenic effects, and it can promote weight loss
TRPV1↑, (TRPV1), to which capsaicin binds specifically.
STAT3↓, capsaicin may inhibit signal transducer and activator of transcription 3 (STAT3), but the minimal concentration needed to inhibit STAT3 (50 M) is substantially higher than the concentration required to stimulate TRPV1 (1–5 M)
Ca+2↑, mechanisms appear to involve accumulation of intracellular Ca2+, generation of reactive oxygen species, disruption of mitochondrial membrane potential and upregulation of the transcription factors NF-κB and STATS.
ROS↑,
MMP↓,
*neuroP↑, Capsaicin has demonstrated therapeutic potential in several animal models of Alzheimer's disease (AD).
*tau↓, capsaicin substantially ameliorated synaptic damage and tau hyperphosphorylation induced by cold water stress.
*Inflam↓, capsaicin appeared to activate TRPV1 in M1/M2 dopaminergic neurons, which may alleviate neuro-inflammation and oxidative stress from activated glia
*ROS?,

3854- CAP,    Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice
- in-vivo, AD, NA
*Aβ↓, capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice.
*cognitive↑, Our present findings further support the protective effects of chili consumption on cognition.
*APP↓, capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10).
*MMP-10↝,
*p‑tau↓, capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration.
*Inflam↓,
*neuroP↑,
*Risk↓, The incidence of AD in west China (3.99/1000 person-years) is lower than that in the east (5.58/1000 person-years)11, and in the west, the proportion of dishes with chili is higher and the pungency degree is greater than in the east
*TNF-α↓, reduced levels of proinflammatory factors, including TNF-α, IFN-γ, and IL-6
*IFN-γ↓,
*IL6↓,
*PPARα↑, apsaicin might activate ADAM10 via upregulating PPARα.

3855- CAP,    Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice
- in-vivo, AD, NA
*Risk↓, capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over.
*Aβ↓, intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice
*p‑tau↓, capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration.
*Inflam↓,
*neuroP↑,
*cognitive↑, Dietary capsaicin rescues cognition impairment in APP/PS1 mice
*ADAM10↑, capsaicin treatment increased the maturation of ADAM10 and thereby precluded Aβ generation
*PPARα↑, capsaicin also upregulated the levels of PPARα, which could activate ADAM10-mediated proteolysis of APP

5768- CAPE,    Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*antiOx↑, it possesses antioxidant, anti-inflammatory, antimitogenic, and anti-cancer activities, as shown by preclinical studies.
*Inflam↑,
*AntiCan↑,
*NRF2↑, figure 1
*GSK‐3β↑,
*Akt↑,
*PI3K↑, directly activates the PI3/Akt signaling pathway as well as leads to increased phosphorylation of GSK-3β to yield it inactive
*ROS↓, decrease in the reactive oxygen species levels (ROS)
*SOD↑,
*GSH↑,
*MDA↓,
*tau↓, reduced hyperphosphorylation of Tau protein
*neuroP↑, Accorded neuroprotection through increased PI3K activity and eNOS mediated nitric oxide synthesis
*memory↑, CAPE treatment in the doses of 6 mg/kg for 28 days led to an improvement in spatial memory and reduction in the malondialdehyde (MDA),
*AChE↓, Other mechanisms which may contribute to its beneficial effect include the inhibition of acetylcholinesterase activity, which has also been reported by several authors
*other↝, Different studies have demonstrated the effectiveness of CAPE in stroke models through its anti-inflammatory and antioxidant properties.
*lipid-P↓, decreasing membrane fluidity, lipid peroxidation, release of cardiolipin, and Cyt c

6040- CGA,    Protective effect of chlorogenic acid on cognitive impairment in rats with early Alzheimer's disease via Wnt signaling pathway
- in-vivo, AD, NA
*neuroP↑, Chlorogenic acid (CGA) has neuroprotective properties associated with Alzheimer's disease (AD).
*Dose↝, gavage of CGA at a dose of 150 mg/kg/d
*GSK‐3β↓, decreased the expression of inflammatory factors, decreased the expression levels of GSK-3β, GFAP, and tau, and increased the expression levels of DVL2 and β-catenin.
*tau↓,
*β-catenin/ZEB1↑,
*Wnt↑, CGA can protect the cognitive impairment of early AD rats via Wnt signaling pathway. we hypothesized that activation of the Wnt signaling pathway can improve cognitive dysfunction in AD rats.
*memory↑, The results showed that CGA could improve the learning and memory ability and cognitive impairment of AD rats via Wnt signaling pathway
*cognitive↑, The result indicated that the CGA group could effectively improve the learning, memory and cognitive impairment of AD rats
*NRF2↑, CGA had a neuroprotective effect on the CI/R rats by regulating the oxidative stress-related Nrf2 pathway.
*ROS↓,

6169- Cin,    Unlocking the Power of Cinnamon: A Detailed Review of Cinnamon Therapeutic Effects in Chronic Disease Management
- Review, Var, NA - Review, Diabetic, NA - Review, AD, NA - Review, IBD, NA
*neuroP↑, This versatile spice has shown potential as a natural remedy fora wide range of chronic diseases, such as neurodegenerative disorders, type 2 diabetes,cardiovascular problems, and metabolic sy
*AntiDiabetic↑,
*tau↓, Key compounds in cinnamon, particularly cinnamaldehyde, are believed to protect the brain by inhibiting the aggregation of tau and amyloid-beta (Aβ) proteins, both of which are hallmark features of Alzheimer’s disease.
*Aβ↓,
*antiOx↑, cinnamon’s antioxidant and anti-inflammatory properties help mitigate oxidative stress and inflammation in the brain
*Inflam↓,
*ROS↓, Neurochemicalanalysis showed reduced oxidative stress, evidenced by lower levels of malondialdehyde and nitrites, as well as increased reduced glutathione.
*MDA↓,
*GSH↓,
*cardioP↑, es, has long beenutilized in herbal medicine to support cardiovascular health and treat cardiovascular diseases(CVDs
*LDL↓, Specifically, cinnamon can lower levels of LDL (bad) cholesterol andtriglycerides, while increasing HDL (good) cholester
*HDL↑,
*other↝, particularly beneficial for treatinginflammatory bowel diseases (IBD) such as colitis.
*TNF-α↓, lowering levels of inflammatory markers such as TNF-α, IL-6, and MPO, andby downregulating the expression of TLR-4.
*IL6↓,
*MPO↓,
*TLR4↓,
*GutMicro↑, cinnamon can also support a balanced gut microbiota, which is essential for overall digestive health. By inhibiting the growth of harmful bacteria and fungi, while promoting the growth of beneficial microorganisms
*lipid-P↓, can improve ulcerative colitis (UC) in rats by reducinginflammation, lipid peroxidation, and histological damage
*Wound Healing↑, Combining cinnamon oil(CO) with aloe vera (AV) (COVA) has been shown to effectively inhibit bacterial growth and promote wound healing.

3889- Cin,    Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models
- in-vivo, AD, NA
*Aβ↓, cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells.
*cognitive↑, CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior.
*tau↓, cinnamon has an inhibitory effect on Tau aggregation related to AD

3894- Cin,    Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis
- in-vitro, AD, NA
*tau↓, Previously we reported that an aqueous extract of cinnamon has the ability to inhibit tau aggregation in vitro
*ROS↓, Further, these compounds protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation.

3888- Cin,    Cinnamon, a promising prospect towards Alzheimer's disease
- NA, AD, NA
*tau↓, mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-β peptides
*Aβ↓,
*neuroP↑, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways.
*ROS↓,
*Inflam↓,
*cardioP↑, figure 1
*antiOx↑,
*cognitive↑,
*BBB↑, cinnamon compounds may either cross the blood brain barrier (BBB) or probably pass through other peripheral routes
*p‑GSK‐3β↑, Cinnamon increased phosphorylated GSK3 (critical for choline metabolism), inhibited AChE activity and increased neuron number in hippocampus area of these animals
*AChE↓, In sum, cinnamon spp. and its biologically active compounds target every 3 AD hallmarks; inhibition of AChE activity, abeta formation/aggregation and tau phosphorylation

3893- Cin,    Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro
- Review, AD, NA
*tau↓, Ceylon cinnamon (C. zeylanicum) is found to inhibit tau aggregation and filament formation, hallmarks of Alzheimer's disease (AD)
*toxicity↓, Cinnamon extract (CE) was not deleterious to the normal cellular function of tau, namely the assembly of free tubulin into microtubules.

3892- Cin,    Cinnamon from the selection of traditional applications to its novel effects on the inhibition of angiogenesis in cancer cells and prevention of Alzheimer's disease, and a series of functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal, nematicidal, acaracidal, and repellent activities
- Review, AD, NA - Review, Var, NA
*antiOx↑, Cinnamon is known to have antioxidant, antibacterial, anti-inflammatory, and other therapeutic properties.
*Inflam↓,
*cardioP↑, natural remedy to treat serious diseases such as type 2 diabetes, chronic digestion problems, cardiovascular diseases, and even cancer and Alzheimer’s disease.
angioG↓, cinnamon extract (CE) displays anticancer activity5 and inhibits angiogenesis by blocking vascular endothelial growth factor (VEGF) 2 signaling
VEGF↓,
*LDL↓, , and low-density lipoprotein cholesterol (7–27%) for patients who consumed 1 g, 3 g, or 5 g of cinnamon for 40 days.
COX2↓, treatment of melanoma cell lines with CE also induced a decrease in Cox-2 and HIF-1α expression in the tumor tissues that mediate the potent antitumor activity of cinnamon
Hif1a↓,
*Aβ↓, A study found that Cinnamon (肉桂 ròu guì) extract (CEppt) inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells.
*tau↓, he extract of the whole cinnamon effectively inhibited the aggregation of human tau in vitro, and this could be attributed to both proanthocyanidin timer and cinnamaldehyde in CE
*toxicity↓, In one study, the intake of up to 6 g/d of C. cassia for > 40 days did not show any adverse effects.

5798- CRMs,    Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders
- Review, Nor, NA - Review, AD, NA
*GutMicro↑, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production
*neuroP↑, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
*eff↑, ‘Mediterranean diet’ composed of unsaturated fatty acids, fibers, and antioxidants has been shown to help in longevity by shifting the GM towards Bacteroides, Bifidobacterium, and Lactobacillus, with a reduction in the members of Pseudomonadota and B
*Dose↝, AD patients displayed fewer populations of Firmicutes, Proteobacteria, and Actinobacteria, and an increased abundance of Bacteroidetes.
*AMPK↑, major routes through which CRMs function include AMPK, Sirtuin1, mTOR, and Keap1-Nrf2 pathways which have been highlighted in Fig. 2.
*SIRT1↑, CRMs can function as activators of protein (de)acetylases, particularly, SIRT1
*mTOR↓,
*NRF2↑, Quercetin, a CRM led to the activation of Nrf2 and induced expression of antioxidant enzymes.
*p‑tau↓, metformin has shown its effect in reducing tau phosphorylation by inducing protein phosphatase 2A (PP2A) expression via the AMPK/mTOR pathway

6181- Cro,    Crocetin: A Systematic Review
- Review, Var, NA - Review, AD, NA
cardioP↑, According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties.
hepatoP↑,
*neuroP↑,
AntiCan↑,
*AntiDiabetic↑,
*memory↑,
*BioAv↓, poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin.
*ROS↓, Crocetin can act via different mechanisms, such as enhancing the rate of oxygen transport and diffusivity, inhibiting pro-inflammatory mediators, protecting cells from reactive oxygen species (ROS) damage, and stimulating apoptosis in cancer cells
Apoptosis↑,
*lipid-P↓, Myocardial hypertrophy rats Decreases the LPO content and increases the activities of GSH-Px and SOD
*SOD↑,
SOD↓, MCF-7 cells Crocetin (200 μmol/L) Inhibits SOD activity by affecting copper binding sites
ERα/ESR1↓, MCF-7 cells Crocetin glucosyl ester IC50 from 31.25 to 1,000 μg/ml Inhibits estrogen receptor α and HDAC2 mediated signaling cascade
HDAC2↓,
TumCCA↑, KYSE-150 cells Crocetin (0, 12.5, 25, 50, 100, 200 μmol/L) S-phase cell arrest
Bax:Bcl2↑, AGS cells Crocetin (50–240 μmol/L) Decreases the Bcl-2/Bax ratio of AGS cells
IL6↓, HCT116 cells Crocetin (30 µM) Downregulates inflammation-related genes, HMGB1, IL-6, and IL-8
IL8↓,
Shh↓, Cancer stem cells (CSC) Inhibits the expression of Sonic hedgehog (SHH)
COX2↑, HeLa cells Upregulates COX-2 expression
*GSK‐3β↓, Alzheimer’s disease (AD) SH-SY5Y and PC12 cells Inhibits the active forms of GSK3β and ERK 1/2 kinases and significantly reduces the total tau protein and tau protein phosphorylation
*ERK↓,
*tau↓,
*ROS↓, crocetin-induced inhibition of Aβ1-42-induced hippocampal HT22 cell death could be mediated via reduced ROS production.
*GSTs↑, The activities of antioxidant enzymes [GSH-Px, GSH reductase (GR), GST, CAT, and SOD]
*Catalase↑,
*SOD↑,
*BioAv↑, The bioavailability of crocetin can be improved by formulating a crocetin injection

3624- Cro,    Crocus Sativus L. (Saffron) in Alzheimer's Disease Treatment: Bioactive Effects on Cognitive Impairment
- Review, AD, NA
*AChE↓, aqueous and methanolic saffron extract presented a moderate activity as AChE inhibitor (up to 30%),
*memory↑, f 50-200 mg/kg of crocin enhanced memory impairment
*cognitive↑, crocin (30 mg/kg) for 3 weeks significantly improved cognitive impairment caused by intracerebroventricular injection of STZ,
*MDA↑, improved cognitive tasks and produced a significant decrease of malondialdehyde (MDA) levels and increase of total thiol content and glutathione peroxidase (GPx) activity in STZ-lesioned rats
*Thiols↑,
*GPx↑,
*antiOx↑, crocetin is only one and strong antioxidant, providing protection in rescuing cell viability, blocking reactive oxygen species (ROS) production and reducing caspase-3 activation
*ROS↓, crocin can prevent oxidative stress damage to hippocampus, memory and learning impairments
*Casp3↓,
*neuroP↑, neuroprotective effects of crocin against AD
*SOD↑, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase,
*Ach↑,
*ChAT↑,
*BBB↑, shown that crocetin, able to pass through BBB, inhibits fibril Aβ formation,
*Aβ↓,
*tau↓, inhibitory effects of crocin on tau protein neurofibrillary tangles in AD.
*cognitive↑, (15 mg twice a day) or a capsule of placebo (two capsules a day) for 16 weeks. The results of this study indicated that saffron produces a significant improvement in cognitive performance
*Inflam↓, anticholinergic, anti-inflammatory and antioxidant features

6050- CUR,  SeNPs,    Efficacy of curcumin-selenium nanoemulsion in alleviating oxidative damage induced by aluminum chloride in a rat model of Alzheimer's disease
- in-vivo, AD, NA
*cognitive↑, Treatment with a curcumin-selenium nanoemulsion has been shown to enhance behavioural performance and mitigate degenerative changes induced by aluminium chloride (AlCl3)
*AChE↓, This nanoemulsion also reduced the activity of acetylcholinesterase (AChE) and lowered levels of key proteins, including Aβ, p53, tau, nuclear factor erythroid 2-related factor 2 (Nrf2), and tumour necrosis factor-alpha (TNF-α).
*Aβ↓,
*P53↓,
*tau↓,
*NRF2↓,
*TNF-α↓,
*NO↑, it significantly decreased nitric oxide (NO) levels in the brain while enhancing the activity of catalase (CAT) and superoxide dismutase (SOD).
*Catalase↑,
*antiOx↑, The study highlights the antioxidant and anti-inflammatory properties of the curcumin-selenium nanoemulsion, suggesting its potential as a therapeutic option for alleviating AD induced by AlCl3.
*Inflam↓,

6207- CUR,    Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment
- Review, Var, NA - Review, AD, NA
*AntiCan↑, gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity.
*Obesity↓,
*Inflam↓,
*lipid-P↓,
*BioAv↓, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10–20 microM).
*BioAv↑, a myriad of nanoformulations have been developed that either lead to a systemic increase in curcumin or are targeted to specific cells, tissues, or organelles
*BioAv↑, latest generation of curcumin nanoformulations can increase the bioavailability of free curcumin in plasma greater than 100-fold and have superior absorption, cellular uptake, BBB permeability, and tissue distribution
*BioAv↑, In a clinical study, the authors found that 2 g of curcumin administered concomitantly with 20 mg of piperine, an inhibitor of hepatic and intestinal glucuronidation, appeared to promote a significant 2000% increase in the oral bioavailability of cur
*BioAv↑, rats in which piperine pre-administration was performed before receiving curcumin, there was a significant increase in the oral bioavailability of curcumin, especially at 6 h after piperine administration
*BioAv↑, Nanotechnology-based delivery systems such as micelles, liposomes, and polymeric, metal, and solid lipid nanoparticles have also been applied to enhance curcumin bioavailability
*ROS↓, Curcumin was effective against ischemia/reperfusion (I/R) lesions, as well in various experimental models, primarily through antioxidant actions such as scavenging ROSs [153], increasing mitochondrial superoxide dismutase (SOD) activity and decreasin
*mt-SOD↑,
*MDA↓,
*BBB↓, Curcumin has poor bioavailability, especially in the brain, where the BBB further limits its absorption
*Aβ↓, curcumin appears to reduce the production of Aβ also by affecting a second enzyme required for the cleavage of APP
*GSK‐3β↓, the inhibition of GSK3β by curcumin would hinder both Aβ production and tau aggregation
*tau↓,
*neuroG↑, prolonged treatment of aged rats with curcumin stimulates neurogenesis in the hippocampus
*memory↑, chronic curcumin administration improved memory acquisition and consolidation in both adult and aged rats
cardioP↑, curcumin has been investigated to promote cardioprotective effects against chemotherapy-induced cardiotoxicity

6208- CUR,    Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial
- Trial, Nor, NA
*memory↑, Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo . Daily oral Theracurmin may lead to improved memory and attention in non-demented adults.
*Aβ↓, symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.
*tau↓,

3794- CUR,    Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities
- Review, AD, NA
*GSK‐3β↓, Firstly, curcumin can inhibit kinases, such as GSK-3β and Cyclin-Dependent Kinase 5 (Cdk5), that excessively phosphorylate Tau protein
*CDK5↓,
*p‑tau↓,
*IronCh↑, curcumin's metal ion chelating capability contributes to the reduction of free radicals
*ROS↓,
*HO-1↑, upregulating antioxidant enzymes including heme oxygenase 1 (HO-1), superoxide dismutase (SOD), catalase, and enzymes involved in the synthesis of endogenous antioxidants, specifically glutathione (GSH)
*SOD↑,
*Catalase↑,
*GSH↑,
*TNF-α↓, inhibiting the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12,
*IL6↓,
*IL12↓,
*NRF2↑, inducing the production of anti-inflammatory mediators including HO-1/NRF-2, PPARα-γ, and IL-4
*PPARγ↑,
*IL4↑,
*AChE↓, researchers have observed that curcumin can suppress AChE mRNA expression levels, effectively preventing the Cd-induced rise in AChE activity
*Dose↝, While curcumin directly interacts with AChE, its inhibitory activity remains weak (IC50 = 67.69 μM)
*GutMicro↑, curcumin's interaction with gut microbiota exhibits potential anti-AD properties.

3793- CUR,    Curcumin Downregulates GSK3 and Cdk5 in Scopolamine-Induced Alzheimer’s Disease Rats Abrogating Aβ40/42 and Tau Hyperphosphorylation
- in-vivo, AD, NA
*Aβ↓, We found that curcumin-treated AD rats markedly reduced the levels of Aβ40 and Aβ42 in the brain and in the plasma in comparison to untreated AD rats
*p‑tau↓, Moreover, the levels of phosphorylated tau at Ser396 (PHF13), Ser202/Thr205 (AT8), and Aβ40/42 (MOAB2) were decreased significantly in AD rats treated with curcumin.
*GSK‐3β↓, Phospho-GSK3β (Tyr216), the active form of GSK3β, and total GSK3β were significantly decreased in AD rats treated with curcumin.
*CDK5↓, Cdk5 and its activators p35 and p25 were significantly decreased in curcumin-treated AD rats.
*memory↑, Impaired spatial memory and locomotor activity in AD rats were partially reversed by curcumin.

3795- CUR,    Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence
- Review, AD, NA
*antiOx↑, Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties
*Inflam↓,
*AntiAge↑, Its potential anti-aging properties are due to its power to alter the levels of proteins associated with senescence, such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and sirtuins
*AMPK↑,
*SIRT1↑,
*NF-kB↓, preventing pro-aging proteins, such as nuclear factor-kappa-B (NF-κB) and mammalian target of rapamycin (mTOR)
*mTOR↓,
*NLRP3↓, Moreover, curcumin, by inhibiting the NF-κB pathway, can directly restrain the assembly or even inhibit the activation of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome
*NADPH↓, by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and elevating the activity of antioxidant enzymes and consequently lowering reactive oxygen species (ROS)
*ROS↓,
*COX2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1↓,
*IL1β↓, by decreasing IL-1β, IL-17, IL-23, TNF-α, and myeloperoxidase, enhancing levels of IL-10, and downregulating activation of NF-κB
*IL17↓,
*IL23↓,
*TNF-α↓,
*MPO↓,
*IL10↑,
*lipid-P↓, curcumin showed a significant decline in lipid peroxidation and increased superoxide dismutase levels, in addition to a reduction in Aβ aggregation and tau hyperphosphorylation through the regulation of GSK3β, Cdk5, p35, and p25
*SOD↑,
*Aβ↓,
*p‑tau↓,
*GSK‐3β↓,
*CDK5↓,
*TXNIP↓, Curcumin also has an inhibitory role on the thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway
*NRF2↑, well as upregulation of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), HO-1, and γ-glutamyl cysteine synthetase (γ-GCS) in brain cells.
*NQO1↑,
*HO-1↑,
*OS↑, significant improvement in OS, and a positive evolution in memory and spatial learning
*memory↑,
*BDNF↑, Besides that, it promoted neurogenesis through increasing brain-derived neurotrophic factor (BDNF) levels
*neuroP↑, Curcumin can promote neuroprotection
*BACE↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.

3588- CUR,    The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies
- Review, AD, NA
*cognitive↝, Clinical studies are mixed regarding curcumin’s effects on cognitive deficits.
*BioAv↑, Ways to improve curcumin’s bioavailability are required.
*Inflam↓, anti-inflammatory activity can be attributed to the suppression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes via down-regulation of nuclear factor kappa B (NF-κB)
*COX2↓,
*iNOS↓,
*NF-kB↓,
*TNF-α↓, nhibition of several inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a) or interleukin (IL) -1, -2, -6, -8, and -12 (
*IL1↓,
*IL2↓,
*IL6↓,
*IL8↓,
*IL12↓,
*ROS↓, Curcumin’s ability to scavenge free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), provides its antioxidant capacity
*RNS↓,
*antiOx↑,
*BBB↑, Multiple studies in rodents and humans have shown that curcumin crosses the blood brain barrier (BBB)
*BioAv↓, drawback is the low bioavailability due to poor solubility, low absorption, rapid metabolism, and rapid excretion
*cognitive↑, The researchers detected a significant cognitive improvement at both doses compared to the untreated group, while a significant dose-response effect was found throughout time with higher doses of curcumin producing greater cognitive improvement
*memory↑, supplementation may improve memory and result in a number of biochemical alternations leading to suppressed tau aggregation
*tau↓,
*eff↑, Combined curcumin and piperine showed superiority, in a dose dependent manner,

3576- CUR,    Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease
- Review, AD, NA
*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

6780- EGCG,    The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer's disease animal model: A systematic review
- Review, AD, NA
*neuroP↑, Regulation of α-, β-, γ-secretase activity, inhibition of tau phosphorylation, anti-oxidation, anti-inflammation, anti-apoptosis, and inhibition of AchE activity are reported as the main neuroprotective mechanisms.
*tau↓,
*antiOx↑,
*Inflam↓,
*Apoptosis↓,
*AChE↓,
*TNF-α↓, Inhibiting TNF-α/JNK pathway
*JNK↓,
*NGF↑, Increasing the level of NGF. EGCG (2 mg/kg) mouse
*SOD↑, figure 7
*GPx↑, EGCG enhanced the activity of T-SOD and GSH-Px and reduced MDA content in the hippocampus.
*MDA↓,
*NO↓,
*ROS↓,
*iNOS↓,
*COX2↓, anti apoptosis
*BAX↓, EGCG prevented LPS-induced elevation of GFAP, iNOS, and COX-2.
*CHOP↓,
*GRP78/BiP↓,
*Bcl-2↑,
*Dose↑, The highest safe dose for more than a month of treatment allowed by FDA is 800 mg of EGCG daily with food.
*BioAv↑, In preclinical and phase I clinical trials, it has been shown that bioavailability of EGCG is increased when it is consumed on a fasting basis.
*hepatoP↓, However, the rate of hepatotoxicity is also increased

6784- EGCG,    Dietary (−)-Epigallocatechin Gallate (EGCG): State-of-the-Art Advances in Bioactivities, Bioavailability Enhancement Strategies, and Applications in Nutrition and Health
- Review, Nor, NA
*antiOx↑, bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular protective, metabolic regulatory, neuroprotective, gut microbiota-modulating, and antimicrobial properties.
*Inflam↓,
*AntiCan↑,
*cardioP↑,
*neuroP↑,
*GutMicro↑,
*AntiBio↑,
*ROS↓, Figure 1, anti inflammatory
*TNF-α↓,
*IL6↓,
TumCP↓,
*LDL↓, cardioprotective
*NO↓,
*Obesity↓, Metabolic syndrome
*p‑tau↓, nervous system
*Aβ↓,
*NRF2↑, , EGCG has been shown to activate the Keap1/P62/Nrf2 signaling pathway,
*SOD↑, upregulation of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, indirectly diminishing the levels of intracellular oxygen free radicals
*Catalase↑,
*GPx↑,
*NLRP3↓, EGCG also restores autophagy levels, suppresses the activation of the NLRP3 inflammasome by inhibiting the mammalian target of rapamycin signaling pathway
*mTOR↓,
TumCCA↑, Cancer: induce cell cycle arrest and inhibit tumor cell proliferation
NRF2↓, EGCG inhibits CCL5-stimulated lung cancer cell proliferation by down-regulating Nrf2 expression
Apoptosis↑, Inducing Apoptosis in Cancer Cells
SIRT1↓, EGCG activates the mitochondrial apoptotic pathway by downregulating SIRT1 expression to modulate the SIRT1-p53 axis
miR-25-5p↓, In breast cancer, EGCG induces apoptosis by inhibiting miR-25 expression and elevating PARP, pre-caspase-3 and pre-caspase-9 protein levels
PARP↑,
Casp3↑,
Casp9↑,
ER Stress↑, in multiple myeloma, EGCG promotes apoptosis by activating the endoplasmic reticulum stress pathway
TumAuto↑, EGCG induces autophagic cell death in breast cancer cells by retaining YAP1 in the cytoplasm and promoting the assembly of the CHMP2B-VPS4B complex
EMT↓, EGCG has been demonstrated to inhibit EMT, invasion, and migration by blocking the TGFβ/Smad signaling pathway
TumCI↓,
TumCMig↓,
TGF-β↓,
Smad1↓,
STAT3↓, EGCG can directly bind to STAT3, reducing nuclear localization and inhibiting the transcription of PLXNC1.
VEGF↓, widely believed that EGCG can block this process by reducing the expression of vascular endothelial growth factor, a key factor in angiogenesis,
angioG↓, The inhibition of angiogenic mimicry by EGCG through the Twist/VE-calmodulin/AKT pathway has also been demonstrated in prostate cancer cells
Imm↑, Acting as an Immunomodulator
EGFR↓, EGCG possesses the ability to interact with EGFR and inhibit activity, strengthening the anticancer evidence for EGCG
*GutMicro↑, EGCG can regulate the balance of gut flora. For example, EGCG can inhibit the growth of harmful bacteria such as Escherichia coli and Salmonella, while promoting the proliferation of probiotics like Bifidobacterium and Lactobacillus
*Bacteria↓, Antibacterial and Antiviral Properties of EGCG
*AntiViral↑,
*BioAv↓, EGCG, its low bioavailability in the human body limits clinical efficacy.
*BioAv↑, Nanotechnology strategy of EGCG.
*eff↑, Co-encapsulation assay of EGCG with quercetin shows that the two synergistically enhanced the antioxidant capacity of EGCG
*BioAv↑, Combining EGCG with resveratrol increases its solubility and significantly improves its absorption in the small intestine.
eff↑, combination of EGCG and curcumin inhibits the activity of metabolic enzymes, reduces the rate of metabolism in the liver and enhances its antitumor efficacy
ChemoSen↑, synergistic effects of EGCG combined with chemotherapeutic agents such as 5-fluorouracil, celecoxib, cisplatin, and tamoxifen have also been reported
*toxicity↝, The European Food Safety Authority notes in scientific opinion that daily oral doses of 800 mg or higher of EGCG represent a common starting point for observed cases of liver injury

4290- EGCG,    EGCG impedes human Tau aggregation and interacts with Tau
- in-vitro, AD, NA
*tau↓, Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau.
*Dose↝, The IC50 for Tau aggregation by EGCG was found to be 64.2 μM.
*neuroP↑, EGCG is a known neuroprotective and antioxidant molecule
*antiOx↑,

4291- EGCG,    Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro
- in-vitro, AD, NA
*tau↓, EGCG, abundant in green tea, has long been known to disaggregate tau and other amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain.
*BBB∅, EGCG itself is a poor therapeutic candidate owing to its polyphenolic molecular structure, which results in unfavorable drug-like properties and restricts brain penetration.

3591- EGCG,    Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats
- in-vivo, AD, NA
*p‑tau↓, EGCG decreased the hyperphosphorylation of Tau in hippocampus
*BACE↓, BACE1 expression and activity as well as the expression of Aβ1-42 were suppressed by EGCG.
*Aβ↓,
*Ach↑, Moreover, EGCG promoted Ach content by diminishing the activity of AchE.
*AChE↓,
*antiOx↑, to improve the antioxidant system and learning and memory function of rats with AD.
*memory↑,
*hepatoP↑, notable components found in coffee have been shown to exert anti-diabetic and hepatoprotective functions
*ROS↓, EGCG Improved the Antioxidant System and Scavenged Free Radicals in AD Rats
*GPx↑, Compared with the AD rats, GPx and T-SOD activities were enhanced in the AD rats with EGCG treatment, especially in the AD rats treated with 250 mg/kg EGCG.
*SOD↑,

3592- EGCG,    (-)-Epigallocatechin-3-gallate ameliorates memory impairment and rescues the abnormal synaptic protein levels in the frontal cortex and hippocampus in a mouse model of Alzheimer's disease
- in-vivo, AD, NA
*neuroP↑, mechanisms by which EGCG exerts its neuroprotective actions in Alzheimer's disease (AD) are presently lacking
*memory↑, long-term oral consumption of EGCG at a relatively high dose (15 mg/kg) improved memory function in SAMP8 mice in the Y-maze and Morris water maze
*p‑tau↓, EGCG treatment also prevented the hyperphosphorylation of tau

6817- EMD,    Emodin inhibits aggregation of amyloid-β peptide 1–42 and improves cognitive deficits in Alzheimer's disease transgenic mice
- in-vivo, AD, NA
*Aβ↓, Aβ deposition in the brains of AD mice treated with a high dose of emodin decreased by 50%–70%.
*tau↓, Emodin reduces levels of β-amyloid, tau aggregation, oxidative stress, and inflammatory response, demonstrating AD therapeutic potential,
*ROS↓,
*Inflam↓,
*cognitive↑, When fed to 8-month-old B6C3-Tg mice for 2 months, high-dose emodin ameliorates cognitive impairment by 60%–70%.

6818- EMD,    Emodin Rescued Hyperhomocysteinemia-Induced Dementia and Alzheimer's Disease-Like Features in Rats
- in-vivo, AD, NA
*Aβ↓, emodin (especially 80 mg/kg/d) reduced the levels of β-amyloid and tau phosphorylation, decreased the levels of β-site amyloid precursor protein-cleaving enzyme 1, and improved the activity of protein phosphatase 2A.
*p‑tau↓,
*PP2A↑,
*cAMP↑, hippocampi of HCY-E40 and HCY-E80 rats, the neuron numbers, levels of synaptic proteins, and phosphorylation of the cAMP responsive element-binding protein at Ser133 were increased
*5LO↓, In addition, depressed microglial activation and reduced levels of 5-lipoxygenase, interleukin-6, and tumor necrosis factor α were also observed.
*IL6↓,
*TNF-α↓,
*ROS↓, Lastly, hyperhomocysteinemia-induced microangiopathic alterations, oxidative stress, and elevated DNA methyltransferases 1 and 3β were rescued by emodin.
*DNMT1↓,

6820- EMD,    The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update
- Review, Nor, NA - Review, Arthritis, NA - Review, AD, NA
*diuretic↑, Emodin has a wide range of biological activities, including diuretic, antibacterial, antiulcer, anti-inflammatory, anticancer and antinociceptive.
*Bacteria↓,
*Inflam↓,
AntiCan↑,
TumCP↓, emodin inhibits processes of neoplasia at the stages of proliferation, invasion and angiogenesis.
TumCI↓,
angioG↓,
*toxicity↓, The results showed that administration of emodin at the doses of 20, 40, and 80 mg/kg for 12 weeks is safe and did not cause any pathophysiological disorders in major organs in mammals.
IFN-γ↑, more interferon gamma (IFN-γ), interleukin (IL)-12 and reactive oxygen species (ROS) and less IL-6, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in he alveolar cavity in the emodin group than those in the control
IL12↑,
ROS↑, In vitro, emodin at the dose of 20 μM had no effect on cell viability in HL-60N1, but increased ROS and decreased autophagy, and thus induced apoptosis in HL-60N2
TNF-α↓,
TNF-α↓,
TGF-β↓,
MAPK↓, Antitumor properties of emodin are associated with inhibiting the activity of tyrosine kinases, such as mitogen-activated protein kinase (MAPK), protein kinase C (PKC), factor kappa-light-chain-enhancer of activated B cells (NF-κB)
PKCδ↓,
NF-kB↓,
HER2/EBBR2↓, emodin suppresses the activity of HER-2/neu tyrosine kinase [55]; whereas, in colon cancer cells, emodin inhibits phosphorylation of vascular endothelial growth factor (VEGF)
VEGF↓,
DNAdam↑, Another antiproliferative mechanism of emodin activity involves induction of DNA damage by the ROS, whose concentration is considerably increased in the cells treated with this anthraquinone.
Necroptosis↑, emodin induces necroptosis in the cells of renal cancer (RCC), which is resistant to conventional cancer therapy, such as chemotherapy or radiotherapy.
Glycolysis↓, and also inhibits glycolysis by downregulation of GLUT1 through ROS-mediated inactivation of the phosphoinositide 3-kinases (PI3K)/AKT signaling pathway.
GLUT1↓,
PI3K↓,
Akt↓,
Casp9↑, increasing active caspase-9, active caspase-3, and bcl-2-like protein 4 (Bax) levels and downregulating Bcl-2.
Casp3↑,
BAX↑,
Bcl-2↓,
eff↑, Li et al. [61] revealed that a bifunctional molecule of β-dihydro-artemisinin-emodin has high antiproliferative activity (suppressing Ki-67 expression),
MMP2↓, Emodin effectively inhibits the expression of the angiogenic-related NF-kB factor, as well as its regulatory factors, including VEGF, MMP-2, MMP-9.
MMP9↓,
eff↑, Combinatorial therapy with emodin and thymoquinone was also efficient in attenuating migration of MCF-7 breast cancer cells, inducing apoptosis, inhibiting cell proliferation, while enhancing cytotoxicity
ChemoSen↑, For example, combination therapy using emodin and doxorubicin sensitize breast cancer cells to doxorubicin by inhibition of proliferation in the DNA damage pathway
P-gp↓, It was demonstrated that emodin downregulated Pgp expression, and enhanced cisplatin-induced apoptosis and DNA damage in the cancer cells
SREBP2↓, suppressing the cholesterol biosynthesis (inhibition the activity of SREBP-2 protein) and inhibiting the expression of the AKT.
eff↑, emodin combined with berberine significantly inhibited the activity of salt-inducible kinases 3 (SIK3), belonging to the AMPK-related kinases, which elevated expressions in breast cancer cells contributing to tumorigenesis.
*other↝, emodin has therapeutic potential for the treatment of various kinds of inflammation, such as pancreatitis, asthma, arthritis, atherosclerosis, myocarditis, glomerulonephritis and Alzheimer’s disease.
*COX2↓, Therapeutic properties of emodin in the treatment of joint inflammation are also associated with inhibition of expression of VEGF, cyclooxygenase 2 (COX-2), hypoxia-inducible factor 1 (HIF-1)α and histone deacetylase (HDAC).
*Hif1a↓,
*HDAC↓,
*tau↓, Emodin effectively prevents abnormal aggregation of tau proteins in PHFs
*PKCδ↑, emodin improved cognitive functions by activating the protein kinase C signaling pathway (PKC), attenuating oxidative stress and inflammatory response in mice with Alzheimer’s disease.
*ROS↓,
*Inflam↓,
AntiAg?,

6824- EMD,    Neuroprotective, Anti-Inflammatory and Antifibrillogenic Offerings by Emodin against Alzheimer’s Dementia: A Systematic Review
- Review, AD, NA
*Inflam?, Emodin is a bioactive phytochemical with potent multimodal anti-inflammatory, antioxidant, and antifibrillogenic properties.
*antiOx↑,
*tau↓, While emodin effectively prevents tau and amyloid-beta (Aβ) oligomerization, it also mitigates their neurotoxicity by attenuating neuroinflammatory, oxidative, and bioenergetic defects.
*Aβ↓,
*neuroP↑, In recent years, several studies have advocated for a robust neuroprotective function of emodin
*ROS↓,
*memory↑, Evidences for emodin-mediated enhancements in memory, learning, and cognition were also found in the literature
*cognitive↑,
*other↝, Well-known sources of emodin include Rheum palmatum,10Polygonum cuspidatum,11Aloe vera,12Polygonum multifarum,13 and Casia obtusofolia.
*AChE↓, potent in vitro inhibition of AChE (IC50 of 21.8 μM), in addition to amelioration of H2O2-induced oxidative damage in PC12 cells
*BACE↓, potent inhibition of the activities of BACE-1 (IC50 of 4.5 μM) and AChE (IC50 of 9.7 μM); and strong and mixed-type inhibition for BACE-1 (Ki of 20 μM) in kinetic studies
*LC3II↓, Inhibition of autophagic (LC3-II and beclin-1)
*Beclin-1↓,
*p‑tau↓, 80 mg/kg/day for 2 weeks (intragastric administration) repression of the levels of BACE-1, Aβ species and phosphorylated-tau, stimulation of CREB signaling
*CREB↑,
*HNE↓, downregulation of Aβ and phosphorylated-tau levels, reduced oxidative damage and 4-HNE levels
*BioAv↓, Bioavailability of exogenously administered emodin suffers from some issues, including its weak intestinal absorption, high rate of elimination, and first-pass metabolism
*BioAv↝, bioavailability of orally supplemented emodin may show appreciable dependence on gender, given that there are four times higher plasma levels of emodin in male rats, compared to females after a single oral dosing of emodin at 8 mg/kg body weight.
*BioAv↑, pretreatment with stilbene glucosides from Radix Polygoni Multiflori prevents glucuronidation of emodin, and increases its plasma concentration upon oral administration
*BioAv↑, cotreatment with piperine was also found to inhibit glucuronide formation of orally administered emodin, while increasing the bioavailability of its free form
*BioAv↑, Nanoemulsification may also decreses the clearance of orally administered emodin, while increasing its brain distribution and bioavailability.
*BioAv↑, Lastly, treatment of emodin with sodium hydroxide to form its sodium salt may represent another strategy for improving the solubility and bioavailability of emodin
BioAv↑, ultrasound-sensitive emodin-containing lecithin-based nanoformulations squamous cell carcinoma FaDu and CAL-27 cells neck squamous cell carcinoma sonodynamic therapy-based beneficial actions
*HO-1↑, figure 3, neuroproctive
*PKCδ↑,
*Akt↑,
*NLRP3↓,
*NF-kB↓,
*TLR3↓,


Showing Research Papers: 1 to 50 of 132
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 132

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   MFN2↑, 1,   NRF2↓, 1,   ROS↑, 3,   SOD↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,   SIRT1↓, 1,   SREBP2↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↑, 3,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3↑, 2,   cl‑Casp3⇅, 1,   Casp9↑, 3,   Cyt‑c↑, 1,   MAPK↓, 1,   MAPK↝, 1,   Necroptosis↑, 1,   p38↑, 1,   survivin↓, 1,   TRPV1↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,   miR-25-5p↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,   HSP70/HSPA5↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,   PARP↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 3,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   HDAC2↓, 1,   mTOR↝, 1,   PI3K↓, 1,   Shh↓, 1,   STAT3↓, 2,  

Migration(tgid=13) ⓘ

AntiAg?, 1,   Ca+2↑, 1,   MMP2↓, 1,   MMP9↓, 1,   PKCδ↓, 1,   Smad1↓, 1,   TGF-β↓, 2,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 3,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 4,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 2,   COX2↑, 1,   IFN-γ↑, 1,   IL12↑, 1,   IL6↓, 1,   IL8↓, 1,   Imm↑, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

ERα/ESR1↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   ChemoSen↑, 3,   Dose↝, 1,   eff↑, 6,   Half-Life↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   ERα/ESR1↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2,   cardioP↑, 2,   hepatoP↑, 1,   Obesity↓, 1,  
Total Targets: 79

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 2,   diuretic↑, 1,   TRPA1↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,   antiOx↑, 20,   Catalase↑, 6,   GPx↑, 6,   GSH↓, 1,   GSH↑, 7,   GSR↑, 1,   GSTs↑, 2,   HDL↑, 1,   HK1↑, 1,   HNE↓, 1,   HO-1↑, 9,   HO-2↓, 1,   lipid-P↓, 11,   MDA↓, 5,   MDA↑, 1,   MPO↓, 2,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 12,   RNS↓, 1,   ROS?, 1,   ROS↓, 32,   SOD↑, 11,   mt-SOD↑, 1,   TAC↑, 1,   Thiols↑, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

Ferritin↑, 1,   IronCh↑, 3,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 3,   cAMP↑, 1,   CREB↑, 1,   GlucoseCon↑, 2,   Glycolysis↑, 1,   LDL↓, 5,   NADPH↓, 1,   NADPH↑, 1,   PDH↑, 1,   PDKs↓, 1,   PPARα↑, 3,   PPARγ↓, 1,   PPARγ↑, 2,   SIRT1↑, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Akt↑, 6,   p‑Akt↑, 1,   Apoptosis↓, 2,   BAX↓, 1,   Bcl-2↑, 2,   Casp1↓, 1,   Casp3↓, 3,   iNOS↓, 3,   JNK↓, 1,   MAPK↓, 1,   TRPV1↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 5,   other↝, 4,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↓, 1,   GRP78/BiP↓, 1,   HSPs↝, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1,   Beclin-1↑, 1,   LC3II↓, 1,   LC3II↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNMT1↓, 1,   P53↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,   GSK‐3β↓, 11,   GSK‐3β↑, 1,   p‑GSK‐3β↑, 2,   HDAC↓, 1,   mTOR↓, 3,   neuroG↑, 1,   PI3K↓, 1,   PI3K↑, 4,   Wnt↑, 1,  

Migration(tgid=13) ⓘ

5LO↓, 2,   APP↓, 2,   Ca+2↓, 1,   CD31↑, 1,   CDK5↓, 3,   MMP-10↝, 1,   MMP3↓, 1,   N-cadherin↑, 1,   PKCδ↑, 2,   TXNIP↓, 1,   VCAM-1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1,   Hif1a↓, 1,   Hif1a↑, 2,   NO↓, 3,   NO↑, 1,   VEGF↑, 3,  

Barriers & Transport(tgid=15) ⓘ

BBB↓, 1,   BBB↑, 6,   BBB∅, 1,   GLUT3↑, 2,   GLUT4↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CB2 / CNR2↑, 1,   COX1↓, 1,   COX2↓, 5,   IFN-γ↓, 1,   IL1↓, 1,   IL10↑, 1,   IL12↓, 2,   IL17↓, 1,   IL1β↓, 7,   IL2↓, 1,   IL23↓, 1,   IL4↑, 1,   IL6↓, 9,   IL8↓, 1,   Inflam?, 1,   Inflam↓, 27,   Inflam↑, 1,   MCP1↓, 2,   NF-kB↓, 11,   PGE2↓, 1,   TLR3↓, 1,   TLR4↓, 1,   TNF-α↓, 15,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 17,   ADAM10↑, 1,   BChE↓, 5,   BDNF↓, 1,   BDNF↑, 2,   ChAT↑, 4,   MAOA↓, 1,   NGF↑, 1,   tau↓, 33,   p‑tau↓, 18,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 26,   BACE↓, 5,   MAOB↓, 2,   NLRP3↓, 3,   PP2A↑, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 7,   BioAv↑, 15,   BioAv↝, 3,   Dose↑, 1,   Dose↝, 6,   eff↑, 5,   Half-Life↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

Ferritin↑, 1,   GutMicro↑, 5,   IL6↓, 9,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   AntiCan↑, 3,   AntiDiabetic↑, 3,   cardioP↑, 6,   cognitive↑, 25,   cognitive↝, 1,   fatigue↓, 1,   hepatoP↓, 1,   hepatoP↑, 3,   memory↑, 21,   motorD↓, 1,   motorD↑, 1,   neuroP↑, 30,   Obesity↓, 2,   OS↑, 1,   Pain↓, 1,   Risk↓, 4,   Sleep↑, 1,   Strength↑, 1,   toxicity↓, 4,   toxicity↝, 1,   Wound Healing↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1,   AntiViral↑, 2,   Bacteria↓, 2,  
Total Targets: 176

Scientific Paper Hit Count for: tau, tau
9 Curcumin
9 Resveratrol
9 Urolithin
7 EGCG (Epigallocatechin Gallate)
6 Cinnamon
6 Emodin
5 Selenium NanoParticles
5 Shilajit/Fulvic Acid
5 Ginseng
4 Berberine
4 Capsaicin
4 Hydrogen Gas
4 Luteolin
4 Quercetin
4 Vitamin B1/Thiamine
3 Thymoquinone
2 Alpha-Lipoic-Acid
2 Ashwagandha(Withaferin A)
2 Baicalein
2 Bacopa monnieri
2 Caffeic acid
2 Crocetin
2 Folic Acid, Vit B9
2 Ferulic acid
2 Magnetic Fields
2 Mushroom Lion’s Mane
2 Vitamin B3,Niacin
2 Rosmarinic acid
2 Sulforaphane (mainly Broccoli)
2 Vitamin K2
1 1,8-Cineole
1 Aromatherapy
1 Beta-Caryophyllene
1 xanthohumol
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Chlorogenic acid
1 Calorie Restriction Mimetics
1 Phosphatidylserine
1 Ginkgo biloba
1 Honokiol
1 Potassium
1 Lycopene
1 Methylene blue
1 Moringa oleifera
1 Methylsulfonylmethane
1 nicotinamide adenine dinucleotide
1 Phenylbutyrate
1 Piperine
1 Pterostilbene
1 chitosan
1 Rutin
1 S-adenosyl-L-methionine
1 Carvacrol
1 Shankhpushpi
1 Silymarin (Milk Thistle) silibinin
1 Ursolic acid
1 Vitamin A, Retinoic Acid
1 Vitamin B12
1 Vitamin B5,Pantothenic Acid
1 Vitamin D3
1 probiotics
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#:1231  State#:%  Dir#:1
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