AChE Cancer Research Results

AChE, acetylcholinesterase: Click to Expand ⟱
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AChE is an enzyme that rapidly hydrolyzes the neurotransmitter acetylcholine into choline and acetate, terminating cholinergic signals.
- In some cancers, studies have reported reduced AChE activity, which may contribute to an accumulation of acetylcholine.
- Lower levels or loss of AChE expression/activity have been associated with more aggressive tumor behavior and poor prognosis, possibly due to unchecked cholinergic signaling.

For AD (Alzheimer's), AChE inhibitors are used, to allow ACh, and ChAT to increase along with acetyl-CoA
-Natural AChE inhibitors: Ferulic Acid, Caffeic Acid, Rosmarinic Acid, Sage
-AChE inhibitors only temporarily relieve some of the disease’s cognitive symptoms and do not stop the patient’s cognitive loss
-adverse effects such as disorientation, falls, dizziness, and fatigue may occur with these medications and should be used only as recommended

- Natural AChE inhibitors paper
Scientific Papers found: Click to Expand⟱
3269- ALA,    Sulfur-containing therapeutics in the treatment of Alzheimer’s disease
- NA, AD, NA
*AChE↓, ALA activated AChE and increased glucose uptake, thus providing more acetyl-CoA to generate acetylcholine (ACh). (note activated AChE in this review likely should say inhibited!!!)
*GlucoseCon↑,
*ACC↑,
*GSH↑, ALA increased intracellular GSH levels by chelating redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and Aβ aggregation.
*Aβ↓,
*Catalase↑, Levels of several antioxidant enzymes including catalase, GR, glutathione-S-transferase (GST), NADPH, and quinone oxidoreductase-1 (NQO1) were enhanced by ALA
*GSR↑,
*GSTs↑,
*NADPH↑,
*NQO1↑,
*iNOS↓, LA prevented the induction of iNOS, inhibited TNFα-induced activation of NF-κB [42], levels of which are increased in AD.
*NF-kB↓,
*lipid-P↓, ALA reduced the levels of lipid peroxidation products
*BBB↑, ALA could easily cross the blood–brain barrier (BBB)
*memory↑, ALA treatment significantly improved the spatial memory and cognition capacity of the mice in the Morris water maze and novel object recognition test.
*cognitive↑,
*antiOx↑, antioxidant and anti-inflammatory activities of ALA
*Inflam↓,

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↑,

6598- Anamu,    Amazonian Plants: A Global Bibliometric Approach to Petiveria alliacea L. Pharmacological and Toxicological Properties
- Review, Var, NA
*AChE↓, Acetylcholinesterase inhibition and antioxidant activity properties of Petiveria alliacea L.
*antiOx↓,
ATP↓, A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases beta-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice
*toxicity↓, In general, the tried extracts and fractions showed low toxicity, except for the described toxicity against cancer cells [48], based on their potential anticancer property.

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

3887- Api,    The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice
- in-vivo, AD, NA
*Inflam↓, anti-inflammatory, anticarcinogenic, and free radical-scavenging activities.
*ROS↓,
*Aβ↓, Recent studies revealed its protective effects against amyloid-β (Aβ)-induced neurotoxicity, but the mechanism was unclear. I
*memory↑, involving improvement of the learning and memory capabilities,
*AChE↓, improvement of cholinergic system involving the inhibition of AChE activity and elevation of ACh level, and modification of BNDF, TrkB, and phospho-CREB levels.
*Ach↑,
*Dose↑, Apigenin, at doses of 10 mg/kg and 20 mg/kg, promoted learning and memory
*BDNF↑, apigenin also increased BDNF level and up-regulated its receptor TrkB and pCREB in A25-35 -induced amnesic mice.
*TrkB↑,
*p‑CREB↑,
*BBB↑, Additionally, we found that treatment with apigenin was effective in preserving anatomical and functional integrity of the BBB per- meability.
*Ca+2?, A relevant effect of apigenin by suppressing the Ca 2+ influx through both voltage- and receptor-operated calcium channels might be attributed to the changes of rCBF

3817- Aroma,    Therapeutic potential of aromatic plant extracts in Alzheimer's disease: Comprehensive review of their underlying mechanisms
- Review, AD, NA
*BChE↓, Essential oils (EOs) from Salvia leriifolia Benth. exhibited high BChE inhibitory.
*AChE↓, Volatile oil from Marlierea racemosa Vell. (Myrtaceae) demonstrated concentration‐dependent inhibition of AChE
*other↓, EOs from the leaves and flowers of Polygonum hydropiper L., 28 sandalwood oil and its chief constituent α‐santalol were reported the AChE, BChE inhibitory efficacy.
*other?, The extract of Rosmarinus officinalis L. leaf led to improved long‐term memory in scopolamine‐induced rats, which can be partially explained by its inhibition of AChE activity in rat brain
*Ach?, It was observed in APP/PS1 mice that 4 weeks of Lemon essential oil treatment could significantly decrease hippocampal AChE, and thus increased ACh levels
*eff↑, Most studies have found that terpenoids in aromatic plant extracts are the main anticholinesterase active components
*antiOx↑, aromatic plant extracts for their potent antioxident and free radical scavenging properties
*ROS↓, Several compounds like safranal, linalool, and SHXW essential oil have been found to decrease ROS levels induced by Aβ in rats or mouse
*cognitive↑, aromatic plant extracts can improve cognitive function, reduce agitation, and improve sleep quality in AD patients.
*Mood↑,
*Sleep↑,

3821- Aroma,    Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants
- Review, AD, NA
*cognitive↑, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects.
*AChE↓, Recently, Ayaz et al. (2015) reported the AChE, BChE inhibitory and free radicals scavenging efficacy of EOs from the leaves and flowers of Polygonum hydropiper.
*BChE↓,
*ROS↓,
*other↓, , Ahmad et al. (2016) reported the anti-cholinesterase and antiradicals potentials of EO from Rumex hastatus D. Don. GC-MS analysis of EO revealed the presence of 123 compounds. I
*other↓, (Ahmad et al., 2016). Okello et al. (2008) reported the in vitro AChE, BChE inhibitory activity of flower oil from Narcissus poeticus L. belonging to family Amaryllidaceae.
*other↓, The EO from Marlierea racemosa Vell. (Myrtaceae) were evaluated by Souza et al. (2009) against AChE enzyme.
*other↓, C. salvifolius exhibited AChE inhibitory activity with IC50 value of 58.1 μg/ml. Whereas, C. libanotis, C. creticus and C. salvifolius showed significant inhibitory activities against BChE with IC50 values of 23.7, 29.1 and 34.2 μg/ml respectively.
*other↓, Rosemary EO also possess moderate AChE inhibitory activity and can synergistically act with 2-pinene and 1,8-cineole.
*memory↑, Owing to the memory enhancing capabilities of Salvia lavandulifolia Vahl (Spanish sage),
*BACE↓, EOs can inhibit the activity of BACE1 to hamper the Aβ load.
*Mood↑, Lavandula angustifolia Mill. and Melissa officinalis L. belonging to Lamiaceae for the management of agitation in individuals with severe dementia. The sedative and calming effect of both EOs is already established which can contribute in consolidati
*motorD↑, lavender EO: locomotor activity and motor functions were improved in animal models.

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

5425- ASTX,    Multiple roles of fucoxanthin and astaxanthin against Alzheimer's disease: Their pharmacological potential and therapeutic insights
- in-vivo, AD, NA
*neuroP↑, fucoxanthin and astaxanthin, natural carotenoids abundant in algae, has shown to possess neuroprotective properties through antioxidant, and anti-inflammatory characteristics in modulating the symptoms of AD.
*antiOx↑,
*Inflam↑,
*AChE↓, Fucoxanthin and astaxanthin exhibit anti-AD activities by inhibition of AChE, BuChE, BACE-1, and MAO, suppression of Aβ accumulation.
*BACE↓,
*MAOA↓,
*Aβ↓,
*memory↑, Recently, Che, Li (Che et al., 2018) reported that astaxanthin possessed memory enhancement.
*MDA↓, Astaxanthin, as an antioxidant, helps to reduce oxidative stress by lowering malondialdehyde (MDA) levels and increasing SOD activity by activation of the NrF2/HO-1 pathway
*SOD↑,
*NRF2↑,
*HO-1↑,
*NF-kB↓, astaxanthin showed NFκB inhibitory activity which caused the downregulation of BACE-1 expression, resulting in Aβ reduction
*GSK‐3β↓, astaxanthin dose-dependently attenuated the GSK-3β activity
*ChAT↑, astaxanthin could reduce neuroinflammation via reducing iNOS expression and spine loss on the hippocampal CA1 pyramidal neurons, and restoring the ChAT expression in the medial septal nucleus
*iNOS↓,
*ROS↓, astaxanthin treatment decreased the ROS production and enhanced the cell growth.
*BBB↑, Astaxanthin can attenuate neurological dysfunction because of its unique chemical structure and can cross the BBB to enter the brain tissue

3749- BBR,    Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids
- Review, AD, NA
*antiOx↑, Thus, the anti-Alzheimer and antioxidant effects of six protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine)
*AChE↓, Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC50 values ranging between 0.44—1.07 μM for AChE and 3.32—6.84 μM for BChE;
*BChE?,

3754- BBR,  CUR,  EGCG,  Hup,    Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer’s disease: A review
*AChE↓, Berberine (9) has gained considerable attention due to its wide pharmacological potentials and several biological properties, such as acetylcholinesterase and butyrylcholinesterase inhibitory, antioxidant, monoamine oxidase oxidase,
*Aβ↓, amyloid-b peptide level-reducing, cholesterol- lowering and renoprotective activities
*LDL↓,
*RenoP↑,
*BChE↓,
*eff↑, Above all, the berberine-pyrocatechol hybrid (14) showed a strong AChE inhibitor activity (IC50 of 123 ± 3 nM) [34]
*BACE↓, Curcumin: inhibite the rBACE1 activity [42]. In addition, it has made good inhibitory effect on acetylcholinesterase activity
*AChE↓, EGCG promoted brain health, prevented AD progression, and inhibited the AChE activity [52,53].
*eff↑, EGCG could enhance the effect of huperzine A on inhibiting AChE.

3633- BBR,  LT,  Cro,  QC,    Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy
- Review, AD, NA
*AChE↓, Alzheimer's disease (AD) is a main cause of dementia, accounting for up to 75% of all dementia cases. Pathophysiological processes described for AD progression involve neurons and synapses degeneration, mainly characterized by cholinergic impairment.
*AChE↓, Fig1: Berberine(1uM), Luteolin(80uM), Crocetin(100uM), Quercetin(120uM)

3677- BBR,    Berberine: A Potential Multipotent Natural Product to Combat Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, multiple activities of berberine, including antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory,
*AChE↓, inhibit AChE with an IC50 of 0.44 μM
*BChE↓, BChE inhibitor and the corresponding IC50 was estimated to be 3.44 μM
*MAOA↓, inhibitory activity on MAO-A with an IC50 value of 126 μM
*Aβ↓, monoamine oxidase inhibitory, amyloid-b peptide level-reducing and cholesterol-lowering activities.
*LDL↓, effectively reduce serum cholesterol and LDL-cholesterol levels in hyperlipidemic hamsters and human hypercholesterolemic patients
*ROS↓, First, it was reported that berberine can scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS)
*RNS↓,
*lipid-P↓, Secondly, berberine can inhibit lipid peroxidation
*Dose↝, berberine can inhibit AChE with an IC50 of 0.44 μM
*MAOB↓, inhibition of berberine against MAO-B: IC50 was estimated to be 98.4 μM
*memory↑, beneficial effect of berberine in ameliorating memory dysfunction in a rat model of streptozotocin-induced diabetes
*toxicity↓, Berberine is generally considered to be non-toxic at doses used in clinical situations and lacks genotoxic, cytotoxic or mutagenic activity
*BBB↑, Berberine can be administered orally [67] and pass through the blood-brain barrier

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↓,

3683- BBR,    Characterization of the anti-AChE potential and alkaloids in Rhizoma Coptidis from different Coptis species combined with spectrum-effect relationship and molecular docking
- NA, AD, NA
*AChE↓, columbamine, berberine and palmatine were the most important AChE inhibitors that could be used as quality markers to select RC drugs for Alzheimer’s disease treatment.

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

5633- BCA,    Mechanisms Behind the Pharmacological Application of Biochanin-A: A review
- Review, Var, NA - Review, AD, NA
*AntiDiabetic↑, Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action.
*neuroP↑, Biochanin-A has been shown to have a potential neuroprotective impact by modulating multiple critical neurological pathways.
*toxicity↓, Unlike chemical agents such as chemotherapeutic agents, isoflavones have shown zero toxicity to humans
*CYP19↓, Biochanin-A inhibits CYP19 and negatively affects the synthesis of oestrogen in the body which enhances the anti-oestrogenic property in hormone-influenced cancer such as prostate cancer and breast cancer
p‑Akt↓, Biochanin-A inhibits Akt phosphorylation thereby downregulates mTOR signals and disrupts the cell cycle.
mTOR↓,
TumCCA↑,
P21↑, Biochanin-A cause apoptosis in lung cancer by increasing p21, caspase-3, and Bcl-2 levels. It lowers E-cadherin and blocks metastasis.
Casp3↑,
Bcl-2↑,
Apoptosis↑,
E-cadherin↓,
TumMeta↓,
eff↑, The synergism of biochanin-A with 5-fluorouracil evidenced in Caco-2 and HCT-116 cell lines indicates the modulatory influence of biochanin-A in colon cancer treatment.
GSK‐3β↓, It blocked the “Akt and GSK3β phosphorylation and boosted the degradation of β-catenin” ( Mahmoud et al., 2017).
β-catenin/ZEB1↓,
RadioS↑, Biochanin-A when combined with gamma radiation on HT29 cells, which is resistant to radiation, had revealed a reduction in cell proliferation.
ROS↑, Raised levels of ROS, lipid peroxidation, MMP, caspase-3 have been observed more in the treatment group with significant apoptosis
Casp1↑,
MMP2↓, biochanin-A influenced the tumour invasion capacity by lowering matrix-degrading enzymes (MMP 2 and MMP 9) tested in U87MG cells
MMP9↓,
EGFR↓, Biochanin-A by lowering EGFR, p-ERK (Extracellular signal related kinases), p-AKT (Protein kinase-B), c-myc, and MT-MMP1 (Membrane type matrix metalloproteinase) activation, inhibited cell survival.
ChemoSen↑, Biochanin-A synergistically improved temozolomide anti-cancer ability in GBM
PI3K↓, Cell signalling pathways MAP kinase, PI3 kinase, mTOR, matrix metalloproteases, hypoxia-inducible factor, and VEGF were inhibited by biochanin-A, making it suitable in treating GBM
MMPs↓,
Hif1a↓,
VEGF↓,
*ROS↓, anti-diabetic mechanism of biochanin-A is by decreasing oxidative stress
*Obesity↓, strongly suggest that biochanin-A has therapeutic potential in the treatment of obesity and the prevention of cardiovascular disease
*cardioP↑,
*NRF2↑, Biochanin-A up-regulated the Nrf-2 pathway while suppressing the NF-κB cascade,
*NF-kB↓, By activating the Nrf-2 pathway and inhibiting NF-κB activation, biochanin-A may reduce obesity and its related cardiomyopathy by decreasing oxidative stress and inflammation
*Inflam↓,
*lipid-P↓, cardio-protective effects by controlling lipid peroxidation
*hepatoP↑, biochanin-A influence the elevated hepatic enzyme level, such as AST, ALP, ALT, bilirubin, etc., and found to be a promising molecule in hepatotoxicity models
*AST↓,
*ALP↓,
*Bacteria↓, The results indicate that biochanin-A may be an effective alternate to antibiotics for alleviating SARA in cattles
*neuroP↑, the neuroprotective effects of biochanin-A might be attributed to the activation of the Nrf2 pathway and suppression of the NF-κB pathway
*SOD↑, Biochanin-A reduced oxidative stress in the brain by augmenting SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) and repressing MDA (malondialdehyde) levels.
*GPx↑,
*AChE↓, Acetylcholinesterase activity was found decreased in a dose-reliant manner amongst biochanin-A treated animals
*BACE↓, Biochanin-A non-competitively inhibited BACE1 with an IC 50 value of 28 μM.
*memory↑, estore learning and memory deficits in ovariectomized (OVX) rats.
*BioAv↓, The bioavailability of biochanin-A is poor.

6511- BCP,    Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene: A Focus on the Nervous System
- Review, AD, NA
*CB2 / CNR2↑, selective cannabinoid receptor 2 (CB2) agonist
*Bacteria↓, numerous pharmacological activities such as antibacterial (e.g., Helicobacter pylori), antioxidant, anti-inflammatory, analgesic (e.g., neuropathic pain), anti-neurodegenerative and anticancer properties.
*antiOx↑,
*Inflam↓,
*NP/CIPN↓,
*neuroP↑,
AntiCan↑,
*ROS↓, β-caryophyllene in reducing oxidative stress and mitochondrial dysfunction, and its possible links with neuroprotection.
*mtDam↓,
*GSH↑, β-caryophyllene (50 mg/kg/day, i.p. for 4 weeks) ↑ GSH, SOD and CAT. Inhibit lipid peroxidation. ↓ IL-1β, IL-6, and TNF-α levels. ↓ COX-2 and iNOS expression.
*SOD↑,
*Catalase↑,
*lipid-P↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*COX2↓,
*iNOS↓,
*NRF2↑, β-caryophyllene (34, 102 and 306 mg/kg/day, p.o.). ↑ Nrf2 and HO-1 expression. Restored SOD and CAT activity and expression.
*HO-1↑,
*AChE↓, Syzygium aromaticum (L.) Merr. and L.M. Perry (0.05 mL/kg and 0.1 mL/kg) ↓ AChE activity, lipid peroxidation levels

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.

5560- betaCar,    β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer's Disease
- in-vivo, AD, NA
*cognitive↑, The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments.
*AChE↓,
*Aβ↓,

5564- betaCar,    β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer’s Disease
- Review, AD, NA
*AChE↓, β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity.
*cognitive↑, The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments.

5473- BM,    Bacopa monnieri: Preclinical and Clinical Evidence of Neuroactive Effects, Safety of Use and the Search for Improved Bioavailability
- in-vivo, AD, NA - in-vivo, Park, NA
*neuroP↑, results in reducing symptoms and protecting against neurodegeneration.
*toxicity∅, Bacopa monnieri has been found to be generally non-toxic, with no serious side effects reported.
*AChE↓, The neuroprotective effect of Bacopa monnieri was likely due to its ability to inhibit acetylcholinesterase activity rather than mitigating glutamate-induced toxicity.
*ROS↓, neurons treated with the extract exhibited lower levels of reactive oxygen species, suggesting a reduction in intracellular oxidative stress and an extension of neuronal lifespan.
*antiOx↑, The extract also demonstrated antioxidant properties and inhibited lipid peroxidation
*lipid-P↓,
*cognitive↑, on 72 mice, it was shown that supplementation with Bacopa monnieri (100 mg/kg for 180 days) significantly improved cognitive function.
*memory↑, 60 healthy, elderly volunteers taking 300 mg and 600 mg of Brahmi showed reduced acetylcholinesterase activity, which resulted in improved attention and memory.
*Dose↝, Ethanol extract was most commonly used in the studies. Doses are usually in the range of 300 to 600 mg daily.
*BioAv↓, Bacoside A is one of the main active compounds found in Bacopa monnieri. However, its water insolubility results in low bioavailability when administered orally.
*TumCCA↑, It has been shown to induce cell cycle arrest and apoptosis in colorectal cancer cell lines
*BBB↝, Studies were also conducted in which, similarly to the aforementioned approach, formulated solid lipid nanoparticles (SLNs) were used to facilitate the transport of the bacoside-rich extract across the blood–brain barrier.

3690- BM,    Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease
- Review, AD, NA
*ROS↓, EBm promotes free radical scavenger mechanisms
*5LO↓, reduces lipoxygenase activity reducing lipid peroxidation, increases glutathione peroxidase and chelates iron.
*lipid-P↓,
*GPx↑,
*IronCh↑,
*neuroP↑, EBm was seen to protect the cholinergic neurons and reduce anticholinesterase activity comparable to donepezil, rivastigmine, and galantamine.
*AChE↓,
*memory↑, EBm improved the total memory score and maximum improvement was seen in logical memory and paired associate learning in humans and reversed phenytoin-induced memory impairment in experimental model.
*toxicity↓, Mild nausea and gastrointestinal upset are seen in humans.
*SOD↑, EBm was administered to the rats for 21 days. It showed increase in activity of enzymes SOD, CAT, and GPx in prefrontal cortex, hippocampus, and striatum. I
*Catalase↑,
*cognitive↑, administration in indicated doses may act as a remedy for age-associated memory and cognitive decline in AD.
*ChAT↑, OBX reduced cholinergic activity and hence also ChAT in hippocampus. Subsequent administration of EBm and tacrine to the substrate, however, reversed this effect
*Ach↑,
*BP↓, Brahmi decreased systolic and diastolic blood pressure without significantly affecting heart rate.

3514- Bor,  CUR,    Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta
- in-vivo, AD, NA
*DNAdam↓, Co-administration of BA and curcumin on synaptosomes exposed to Aβ1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities.
*MDA↓,
*AChE↓,
*neuroP↑, BA and curcumin had protective effects on rat brain synaptosomes against Aβ1-42 exposure.
*ROS↓, BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of Aβ1-42 exposed.
*NO↓, Synaptosomes treated with BA showed a significant reduction in MDA and NO levels

3786- Bor,    New and potential boron-containing compounds for treatment of Alzheimer's disease and cancers
- Analysis, AD, NA - Analysis, Var, NA
*AChE↓, Based on our findings, compounds (1-4) demonstrated more potent AChE inhibitory activity compared to tacrine, which is an FDA-approved AChE inhibitor.
TumCP↓, compound 4 exerted an antiproliferative activity against various human cancer cell lines (32.91 ± 4.92 µM in HT29 and 42.38 ± 2.73 µM in MCF-7).

3866- Bos,    Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties
- Review, AD, NA
*neuroP↑, therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD).
*Inflam↓, main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD
*AChE↓, It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels
*Ach↑,
*NRF2↑, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity.
*NF-kB↓,
*Aβ↓, inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD

2772- Bos,    Mechanistic role of boswellic acids in Alzheimer’s disease: Emphasis on anti-inflammatory properties
- Review, AD, NA
*neuroP↑, (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD
*Inflam↓,
*AChE↓, inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels
*Choline↑,
*NRF2↑, BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD
*NF-kB↑,
*BBB↑, AKBA has efficiently abled to cross the blood brain barrier (BBB)
*BioAv↑, bioavailability of AKBA was significantly higher in case of sublingual route when compared to intranasal administration, as demonstrated by area under curves (AUCs) analysis
*Half-Life↓, half-life of the drug was about six hours and peak plasma levels of the drug reach 30 hrs after oral administration of 333 mg of BSE.
*Dose↝, drug needs to be administered at a dosing interval of 6 hrs
*PGE2↓, BAs possessed anti-inflammatory activity by inhibiting microsomal prostaglandin E2 synthase-1 (mPGES1)
*ROS↓, prevented oxidative stress-induced neuronal damage and cognitive impairment because of the antioxidant, anti-inflammatory and anti-glutamatergic effects
*cognitive↑,
*antiOx↑,
5LO↓, AKBA significantly reduced pro-inflammatory mediators such as 5-LOX, TNF-α, IL-6 levels and improve cognition
*TNF-α↓,
*IL6↓,
*HO-1↑, AKBA shows neuroprotective effects against ischaemic injury via nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade activation

4270- Bos,    Boswellic acids ameliorate neurodegeneration induced by AlCl3: the implication of Wnt/β-catenin pathway
- in-vivo, AD, NA
*memory↑, BA significantly improved learning and memory impairments induced by AlCl3 treatment.
*AChE↓, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aβ) expression
*Aβ↓,
*TNF-α↓, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), inhibited lipid peroxidation, and increased total antioxidants in the brain.
*IL1β↓,
*lipid-P↓,
*TAC↑,
*BDNF↑, Indeed, BA significantly suppressed AlCl3-induced decrease of brain-derived neurotrophic factor, pGSK-3β (Ser 9), and β-catenin.
*β-catenin/ZEB1↑,
*Dose↑, BA (250 mg/kg) showed a significant protective effect compared to a lower dose.

6551- BSB,    α-bisabolol β-d-fucopyranoside (ABFP) ameliorates scopolamine-induced memory deficits through cholinesterase inhibition and attenuation of oxidative stress in zebrafish (Danio rerio)
- in-vivo, AD, NA
*ROS↓, reduced oxidative stress and damage in ABFP-treated fish
*AChE↓, brain homogenate from ABFP-treated fish showed decreased acetylcholinesterase enzyme activity.

6550- BSB,    α-bisabolol β-D-fucopyranoside as a potential modulator of β-amyloid peptide induced neurotoxicity: An in vitro &in silico study
- in-vivo, AD, NA
*AChE↓, in vitro studies showed that the compound possess significant ability to inhibit the AChE enzyme apart from exhibiting antioxidant, anti-aggregation and disaggregation properties.
*antiOx↓,
*neuroP↑, Furthermore, the compound was able to protect the Neuro2 a cells against Aβ25-35 peptide induced toxicity.

6542- BSB,    Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol
- Review, Var, NA - Review, Park, NA - Review, AD, NA
AntiCan↑, Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial.
*neuroP↑,
*cardioP↑,
*AntiBio↑,
*BioAv↑, Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant wit
*toxicity↓,
*BioAv↑, integrated in many cosmetic formulations due to its skin soothing effects, well documented dermal absorption
*motorD↑, improvement in locomotor activity, a reduction in the expression of thiol and a reinstate of the activity of mitochondrial complex-I.
*SOD↑, α-Bisabolol also increased the mRNA level of antioxidants proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product.
*Catalase↑,
*Keap1↑,
*MDA↓, α-Bisabolol attenuated oxidative insult by reducing malondialdehyde (MDA), restoring depleted glutathione (GSH) and improving SOD and CAT activity.
*GSH↑,
*IL1β↓, attenuated neuroinflammation by reducing glial cells activation and subsequent release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and mediators (iNOS and COX-2).
*IL6↓,
*TNF-α↓,
*iNOS↓,
*COX2↓,
*lipid-P↓, α-Bisabolol restored mitochondrial function by preventing mitochondrial lipid peroxidation, cytochrome-C release and most importantly preserving Complex-I activity
*Cyt‑c↓,
*ROS↓, The study concluded that α-Bisabolol safeguarded against the induced upsurge of ROS and nitrite.
*MMP↑, α-Bisabolol treatment also restored mitochondrial membrane potential (MMP) validating its antioxidant effect.
*antiOx↑,
*AChE↓, showed a significant reduction in AChE activity and an ability to avert Ach depletion.
*Apoptosis↓, α-Bisabolol protected cells from Aβ triggered apoptosis by reducing Bax and Caspase-3 and increasing Bcl-2 activity.
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BACE↓, α-Bisabolol inhibitory activity on BACE1 and found a decrease in BACE1 activity following α-Bisabolol treatment
*BChE↓, AChE, BuChE, β-secretase actions were decreased significantly in cells pretreated with α-Bisabolol
*eff↑, The compound clearly illustrated a potent anti-AchE activity of 95.869% similar to the activity of donepezil, a standard drug. I
*Aβ↓, The compound also disaggregated Aβ25–35 peptide and protected against its induced toxicity by increasing neuro2a cells viability [
*ATP↑, figure 2
RadioS↑, α-Bisabolol and Anticancer Effects, figure 3
Cyt‑c↑,
Casp3↑,
Casp8↑,
Casp9↑,
Apoptosis↑,
PARP↑,
BAX↑,
BID↑,
NF-kB↑,
Fas↑,
EGFR↑,
TIMP2↑,
XIAP↓,
COX2↓,
Bak↓,
Bcl-2↓,
P53↑, The expression of p53 (a transcription factors whose products might lead to apoptosis), NF-κB and Fas was increased following α-Bisabolol treatment, indicating their function in mediating α-Bisabolol-induced apoptosis in the cancer cell line.
HER2/EBBR2↓,
FGF↓,
CEA↓,
Akt↓,
TumCCA↑, α-Bisabolol suppresses the cellular proliferation at G2/M cell cycle phase.
*Imm↑, reported that α-Bisabolol boosted the immunity response by T-cell subsets (CD4 and CD8) supplementation in treated mice.
*CD4+↑,
*CD8+↑,
*BBB↑, ↑ BBB penetration
*Pain↓, α-Bisabolol based mouthwash to that of chlorhexidine in reducing pain during brushing
*cardioP↑, α-Bisabolol and Cardioprotection, figure 5
*TBARS↓, rats co-treated with α-Bisabolol showed reduced LOOH and TBARS and increased SOD, CAT and GSH.
*SOD↑,
*Catalase↑,
*GSH↑,
*AntiBio↑, α-Bisabolol demonstrated an antibacterial effect against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa as well as a synergism against S. aureus, when combined with the antibiotic norfloxacin and against E. coli when combined with
*AntiFungal↑, ↓ fungal growth
*GastroP↑, α-Bisabolol and Gastroprotection. oral administration of α-Bisabolol was realized to attenuate gastric damage and to provide cytoprotection in stomach.
*RenoP↑, The nephroprotective effects of α-Bisabolol and the underlying mechanisms are summarized in Table 10.
*creat↓, ↓ creatinine, urea, uric acid
*uricA↓,
*Inflam↓, Anti-Inflammatory Effects of α-Bisabolol
*iNOS↓, ↓ iNOS, COX-2, TNF-α, p65 PGE2, nitrite, IL-6, ↓ MMP13
*COX2↓,
*TNF-α↓,
*IL6↑,
*MMP13↓,

6552- BSB,    Biochemical characterization of chamomile essential oil: Antioxidant, antibacterial, anticancer and neuroprotective activity and potential treatment for Alzheimer's disease
- in-vivo, AD, NA
*TNF-α↓, (TNF-α), amyloid precursor protein (APP), amyloid beta (Aβ), caspase-3, & B-cell lymphoma 2 (Bcl-2) was significantly elevated due to the harmful effect of AlCl3; however, CCO downregulated these values,
*Aβ↓,
*Casp3↓,
*Bcl-2↓,
*neuroP↑, The brain histology of CCO-treated rats showed a significant reduction in neuronal degeneration and improved brain changes, and its histology was close to that of the control brain.
*antiOx↑, could be used as an antioxidant and neuroprotective agent for AD due to its considerable contents of antioxidants and anti-inflammatory compounds.
*Inflam↓,
*AntiBio↑, These compounds are responsible for many of the beneficial effects of chamomile essential oil, including its anti-inflammatory, antimicrobial, and sedative properties (Petronilho et al., 2012);
*AChE↓, they also have an inhibiting effect on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities
*BChE↓,
Dose↝, main compounds in the GC–MS profile were α-Bisabolol, Camazulene, Bisabolol oxide A, 1,6-Dioxaspiro [4.4] non-3-ene, 2-(2,4-hexadiyn-1-ylidene) with contents of 26.1, 25.3, 27.8, and 25.2 % in CCO
Dose↝, we found that α-Pinene and Limonene were more distinct in plants than in the flower
Dose↝, The IC50 of CCO was 200 µg/mL compared to 400 µg/mL for Cisptalin.

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.

3758- CA,  RT,  CGA,    Polyphenols and inhibitory effects of crude and purified extracts from tomato varieties on the formation of advanced glycation end products and the activity of angiotensin-converting and acetylcholinesterase enzymes
- Analysis, AD, NA
*AChE↓, Caffeic acid, caffeoyl-glucose, linocaffein, glucosyl-coumarate, vanillic acid, rutin and TPI values were significantly correlated with BSA-MGO, anti-ACE, anti-AChE and PCLACW parameters
*eff↑, However, chlorogenic acid is probably a more potent ACE inhibitor than caffeic acid due to the number of hydroxyl groups in its structure.

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),

3784- CA,  CGA,    Comparative Study on the Inhibitory Effect of Caffeic and Chlorogenic Acids on Key Enzymes Linked to Alzheimer’s Disease and Some Pro-oxidant Induced Oxidative Stress in Rats’ Brain-In Vitro
- Study, AD, NA
*AChE↓, caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner
*BChE↓,
*eff↑, however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid.
*ROS↓, s preventing oxidative stress-induced neurodegeneration
*neuroP↑, neuroprotective properties

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

5907- CAR,    Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2
- in-vitro, Liver, HepG2
TumCG↓, In this study, we showed that carvacrol inhibited HepG2 cell growth by inducing apoptosis
Apoptosis↓,
Casp3↓, activation of caspase-3, cleavage of PARP and decreased Bcl-2 gene expression
cl‑PARP↑,
Bcl-2↓,
p‑ERK↓, decreasing phosphorylation of ERK1/2 significantly in a dose-dependent manner, and activated phosphorylation of p38
p‑p38↑,
*Bacteria↓, carvacrol has been shown to exhibit anti-microbial, anti-mutagenic, anti-platelet, analgesic, anti-inflammatory, anti-angiogenic, anti-oxidant, anti-elastase, insecticidal, anti-parasitic,cell-protective, AChE inhibitor and anti-tumor activity
*AntiAg↑,
*Inflam↓,
*antiOx↑,
*AChE↓,
AntiTum↑,
MMP↓, classical apoptosis response, including decrease in mitochondrial membrane potential and increase in cytochrome c release from mitochondria, decrease in Bcl-2/Bax ratio, increase in caspase activity and cleavage of PARP and fragmentation of DNA,
Cyt‑c↑,
Bax:Bcl2↑,
Casp↑,
DNAdam↑,
selectivity↑, we found that carvacrol induced stronger effects on hepatocellular carcinoma cells compared to normal human fetal liver cells.

5927- CAR,    Neuroprotective Potential and Underlying Pharmacological Mechanism of Carvacrol for Alzheimer’s and Parkinson’s Diseases
- Review, AD, NA - Review, Park, NA
*memory↑, Carvacrol enhances memory and cognition by modulating the effects of oxidative stress, inflammation, and Aβ25-35-induced neurotoxicity in AD
*cognitive↑,
*ROS↓, reduces the production of reactive oxygen species and proinflammatory cytokine levels in PD
*Inflam↓,
*motorD↑, improves motor functions
*toxicity↓, in general, it is potentially safe for consumption
*TRPV3↑, Carvacrol is a potent agonist of transient receptor potential vanilloid 3 (TRPV3)
*other↓, mitigating oxidative stress (OS)/ADP-ribose (ADPR)-induced TRPM2 and GSK1016790A (GSK)-mediated TRPV4 activations
*antiOx↑, Essential oils, high in carvacrol, have powerful antioxidant properties [85-88] similar to vitamin E, ascorbic acid, and butyl hydroxyl toluene
*LDL↓, Low-density lipoprotein (LDL) is inhibited by carvacrol in vitro and mediates LDL oxidation within an incubation period of 12 h
*COX2↓, suppressing the expression level of cyclooxygenase-2 (COX-2),
*PPARα↑, triggering the peroxisome proliferator-activated receptors (PPAR) α and γ
*NO↓, inhibiting NO production
*AChE↓, Carvacrol's acetylcholinesterase inhibitory action is 10 times higher than thymol's, even though the two compounds have a relatively similar structure
*eff↑, carvacrol nanoemulsion treatment has shown more notable effects compared to carvacrol oil.
*SOD↑, increases superoxide dismutase (SOD) and catalase (CAT) activity
*Catalase↑,
*neuroP↑, neuroprotective effects of carvacrol against cognitive impairments and its potential in AD are shown in Fig. (2)
*BioAv↝, In rabbits, 1.5 g of orally administered carvacrol is progressively absorbed from the intestines, with approximately 30% of the whole dose remaining in the gastrointestinal system and 25% eliminated via urine after 22 h of administratio
*BBB↑, carvacrol in the brain tissues as it easily crosses the blood-brain barrier owing to its low molecular weight (150.2 g/mol) and higher lipophilicity
*BioAv↑, liposomal encapsulation [136], and solid lipid nanoparticles [137], were developed and found bioavailable on oral administration. These formulations exhibit improved solubility, stability, and bioavailability and enhance drug accumulation in the tiss

5926- CAR,    An Updated Review of Research into Carvacrol and Its Biological Activities
- Review, Nor, NA - Review, AD, NA - Review, asthmatic, NA
*Inflam↓, ic, analgesic, anti-inflammatory,antioxidant, and neuroprotective effects.
*antiOx↑,
*neuroP↑, Carvacrol has exhibited notable neuroprotective effects in experimental models of cognitiveimpairment and neurodegenerative diseases
*BioAv↑, advances in encapsulation andnanotechnology have enhanced its stability and bioavailability
*toxicity↓, Compared to phenol, carvacrol and thymol exhibitsignificantly lower toxicity. This makes carvacrol a safer alternative for various applications, frombiological agents to dietary supplements [
*Pain↓, Pain-Relieving Mechanisms of Car
*TRPV3↑, , carvacrol-induced TRPV3 activation enhances lipolysis in adipocytes via theNRF2/FSP1 a
*NRF2↑,
*Ca+2↑, TRPV3 activation in distal colon epithelial cells elevates intracellular Ca²⁺ levels and stimulates ATP release, implicating carvacrol in gut physiology and signaling
*ATP↑,
*5LO↓, s, including the inhibition of angiotensin-converting enzyme 2 (ACE2), lipoxygenase(LOX), and cyclooxygenase (COX) enzyme
*COX2↓,
PGE2↓, arvacrol’s anti-inflammatory effects involve theinhibition of prostaglandin E₂ (PGE₂) production via COX-2
*hepatoP↑, Carvacrol in Hepatic Protection as Natural Antioxidant
*AntiAg↑, Carvacrol has demonstrated significant antiplatelet activity, highlighting its potential therapeutic role in preventing thrombosis
*Diar↓, s essentialoil exhibited antidiarrheal effects in castor oil-induced diarrhea models, potentially mediated bymechanisms involving Kv channel activation and Ca²⁺ channel inhibition
*cardioP↑, em as promising nutraceutical candidates for alleviatingCVD-related complicat
*other↝, Carvacrol was evaluated for its therapeutic potential in managing erectile dysfunction (ED)associated with aging
*chemoPv↑, Chemopreventive Potential of Carvacrol in Detoxification pathways
*cognitive↑, carvacrol(0.5–2 mg/kg) and thymol significantly improved cognitive function in rats
*AChE↓, potent acetylcholinesterase inhibitory activity (IC₅₀: 158.94 μg/mL)
*GastroP↑, . Gastroprotective Effects of Carvacrol and Mechanism
*eff↑, . When combined with polysorbate 80 as a surfactant, carvacrol was efficiently deliveredto embryonic tissues, maintaining bioavailability during the peri-hatching phase
*BChE↓, acrol. The essential oil rich in carvacrol showedstrong inhibitory effects on AChE and butyrylcholinesterase (BChE) [
*CRP↓, d Phase II clinical trial, asthmatic patients whoreceived 1.2 mg/kg/day of carvacrol for two months showed significant improvements in pulmonaryfunction tests and a notable reduction in C-reactive protein levek

5925- CAR,    Neuroprotective effects of carvacrol against Alzheimer’s disease and other neurodegenerative diseases: A review
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*Inflam↓, anti-inflammatory, antioxidant, and AChEI properties
*antiOx↑,
*AChE↓,
*BBB↑, Carvacrol is able to cross the blood brain barrier easily, notably improving its therapeutic efficacy in neurodegenerative disorders
*cardioP↑, prevention of many chronic diseases, such as cancer as well as infectious, cardiovascular and neurodegenerative diseases
*neuroP↑, Extensive researches have revealed carvacrol neuroprotective properties
*memory↑, memory-enhancing activities
*TAC↑, Carvacrol has antioxidant activity and was shown to act as a dietary phyto-additive to boost animal antioxidant status (sharifi-Rad et al., 2018
*ROS↓, carvacrol could protect neuronal injuries against Aluminum-induced oxidative stress leading to lipid peroxidation
*lipid-P↓,
*MDA↓, carvacrol has been indicated to reduce malondialdehyde (MDA) and neuronal cell necrosis, and increase superoxide dismutase (SOD) and catalase (CAT) activity levels in the hippocampus (
*SOD↑,
*Catalase↑,
*NRF2↑, carvacrol activated nuclear factor-erythroid 2-related factor 2 (Nrf2) as an endogenous antioxidant
*cognitive↑, Carvacrol administration (25, 50, and 100 mg/kg) during 21 days attenuated memory impairments and enhanced cognition compared to the control group.
*IL1β↓, Carvacrol administration diminished the expression of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α).
*COX2↓,
*TNF-α↓,
*TLR4↓, carvacrol could significantly decrease Toll-like receptor 4 (TLR4) and increase brain-derived neurotrophic factor (BDNF) expression.
*BDNF↑,
*PKCδ↑, carvacrol and thymol might have protective ability on cognitive function in AD by activation of PKC pathway
*5LO↓, Carvacrol inhibited AChE and lipoxygenase activity that supports its anti-inflammation and anti-Alzheimer effects
*TRPM7↓, Reduced caspase-3 levels, and TRPM7 channels inhibitor
*GSH↑, Antioxidant activity, Increased glutathione
*other↑, revealed a remarkable neuroprotective action of carvacrol in cerebral ischemia in animal models
*Ferroptosis↓, via ferroptosis inhibition by elevating GPx4 expression
*GPx4↑,

6648- Cen,    Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential
- Review, AD, NA
*neuroP↑, According to the literature survey, C. asiatica (gotu kola) has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer's disease, dopamine neur
*Aβ↓,
*ROS↓, dopamine neurotoxicity in Parkinson's disease, and decreasing oxidative stress.
*Wound Healing↑, Monographs of the plant describing mainly its wound healing and memory enhancement effects exist in the European Pharmacopeia
*memory↑,
*Inflam↓, anti-inflammatory [8, 9], antipsoriatic [10], antiulcer [11, 12], hepatoprotective
*hepatoP↑,
*Imm↑, anticonvulsant [14], sedative [15], immunostimulant [16], cardioprotective [17, 18], antidiabetic [19], cytotoxic and antitumor [20, 21], antiviral [22], antibacterial [23], insecticidal [24], antifungal [25], antioxidant
*cardioP↑,
*AntiDiabetic↑,
*AntiFungal↑,
*antiOx↑,
*Dose↝, Presence of several flavonoid derivatives such as quercetin, kaempferol, patuletin, rutin, apigenin, castilliferol (Figure 3), castillicetin, and myricetin has been reported in C. asiatica [35, 39, 42], while isolation of polysaccharides (e.g., cente
*AChE↓, The extract was found to inhibit AChE with 50% of inhibition rate at 150 μg/mL concentration . only the standardized extract was found to inhibit AChE
*BChE↓, ethanol extracts of the plant samples from Turkey and India exerted 46.95 ± 0.94% and 70.30 ± 3.77% against BChE, respectively, and a notable inhibition against TYRO
*Tyro3↓,
*lipid-P↓, showing a neuroprotective effect in old rats by way of bringing about a significant decrease in PCO contents and lipid peroxidation.

6650- Cen,    Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review
- Review, AD, NA
*BioAv↝, madecassoside, asiaticoside, madecassic acid, and asiatic acid are widely distributed in the body and madecassoside, asiaticoside may exert their biological activity through converted into aglycone (madecassic acid, and asiatic acid).
*BioAv↝, C. asiatica enhances the function of the nervous system. It dissolves in methanol, ethanol, and water.
*MDA↓, Male Wistar rats – MDA ↓, GSH ↑, SOD ↑, AChE↓
*GSH↑,
*SOD↑,
*AChE↓,
*memory↑, Male SD rats; hippocampal cell – Spatial working memory↑, Ki-67 cells↑
*Ki-67↑,
*Catalase↑, Male SD rats MAPK SOD↑, LPO↑, CAT↑, GSH↑, dopamine↑, glutamate↑, Syn1↑, Stx1A↑, PI3K↑, PDK1↑, PEBP↓, VMAT2↑, TH ↑, MAPK ↑, BDNF↑, NGF↑
*PI3K↑,
*BDNF↑,
*NGF↑,
*ROS↓, Water extract of CA Tg2576 mice – ROS↓, NRF2↑, GCLC↑, HMOX1↑, NQO1↑, ATP↑, Mt-ND1↑, Mt-ATP6↑, Mt-CO1↑, Mt-CYB↑, oxygen consumption rate↑
*NRF2↑,
*HO-1↑,
*NQO1↑,
*ATP↑,
*OCR↑,
*TNF-α↓, Ethanolic extract of CA Male SD rats – TNF-α↓, BDNF↑
*PP2A↑, Ethanolic extract of CA Male albino Wistar rats PP2A/GSK-3B PP2A↑, GSK-3B↓, Bcl-2↑
*GSK‐3β↓,
*Bcl-2↑,
*TrkB↑, Standardized extract of CA Male Wistar rats – NR2A↑, NR2B↑, BDNF↑,TrkB↑
*NOTCH1↑, Asiatic acid Male SD rats – Notch1↑, SOX2↑, DCX↑, Nrf2↑, nestin↑, p21 positive cells↓, MDA↓
*SOX2↑,
*Nestin↑,
*MDA↓,
*MAOA↓, Asiaticoside-D Worms – MAO-A↓, MAO-B↓
*MAOB↓,
*GPx↑, Previous studies found that C. asiatica and its triterpenoids could effectively increase SOD and GPX activities, activate nuclear factor erythroid-2-related factor 2, improve the cognitive impairment of animals,
*cognitive↑,
*ROS↓, C. asiatica and its triterpenoids could reduce ROS production
*neuroP↑, they reduced related nerve cell apoptosis, increased synaptic density, and improved the survival rate of neural cells
*glucose↓, Methanol extract of CA Male SD rats – Blood glucose ↓, food and water intake ↓, ALT↓, AST↓, PFK ↑, GS ↑, GP↑, glycogen content ↑
*ALAT↓,
*AST↓,
*PFK↓,
*Weight↓, inhibit weight gain
*Inflam↓, (4) ameliorate inflammation,
*AntiDiabetic↑, C. asiatica extract and related components (asiatic acid, madecassoside) for the treatment of endocrine diseases such as diabetes, obesity and osteoporosis are excellent.
*Obesity↓,
*Wound Healing↑, The C. asiatica extract and its triterpenoids had certain therapeutic and relieving effects on acne, baldness, vitiligo, atopic dermatitis, and wounds. C. asiatica extract can effectively promote wound healing in diabetic patients
*cardioP↑, C. asiatica has a positive effect on cardiovascular diseases.
*GutMicro↑, C. asiatica and its triterpenoids also have therapeutic effects on digestive disorders, which is mainly reflected by improved liver fibrosis, colitis, and gastric mucosal damage; and even reduced Helicobacter pylori gastric colonization
*Sepsis↓, Asiatic acid can improve the side effects caused by antibiotics, reverse multidrug resistance (MDR), and reduce sepsis.
*BioAv↑, C. asiatica cream containing 5.12% asiaticoside and 5.1% madecassoside can be completely absorbed by the skin and effectively improve pigmentation and may be used in treating hypertrophic scars

6646- Cen,    Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke
- Trial, Stroke, NA
*eff↑, indicating that gotu kola is as effective as folic acid in improving poststroke VCI.
*memory↑, Gotu kola was shown to be more effective than folic acid in improving memory domain.
*cognitive↑, This study suggested that gotu kola extract is effective in improving cognitive function after stroke.
*AST∅, The analysis showed no significant difference between AST and ALT levels before and after treatment with p value of all groups
*ALAT∅,
*AChE↓, The aqueous extract of the entire gotu kola plant has been revealed to show improvement in learning and memory, inhibition of AChE activity,
*toxicity↓, Gotu kola extract either in 750 mg or in 1000 mg was well tolerated with minimal side effects.

6016- CGA,    Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review
- Review, Var, NA - Review, AD, NA - Review, Diabetic, NA
antiOx↑, CGAs have been associated with health benefits, such as antioxidant, antiviral, antibacterial, anticancer, and anti-inflammatory activity, and others that reduce the risk of cardiovascular diseases, type 2 diabetes, and Alzheimer’s disease.
*Bacteria↓,
AntiCan↑,
*Inflam↓,
*cardioP↑, reduce the risk of cardiovascular disease by suppressing the expression of P-selectin in platelets
*AntiDiabetic↑,
*GutMicro↑, non-absorbed part of 5-CQA and caffeic acid in the human gastrointestinal tract serves as a substrate for beneficial intestinal microbiota,
*eff↑, The fortification of foods with coffee CGAs has the potential to improve the functionality of foods.
*eff↑, exposing them to monopolar pulses of 2 Hz with an interval of 0.5 s and generating an electric field of 28 kV/10 cm with water at 20 °C. The use of an electric field increased radical scavenging activity up to 31% and 11%, for green and roasted coffe
*ROS↓, CGAs are known to exhibit a radical scavenging effect similar to ascorbic acid
*IronCh↑, CGAs can chelate transition metals such as Fe2+ to scavenge free radicals and disrupt chain reactions
*neuroP↑, The neuroprotective mechanisms of coffee are suggested to be related to the anti-inflammatory effects of caffeine and CGAs on A1 and A2 receptors.
*AChE↓, some coffee compounds could inhibit brain acetylcholinesterase and butyrylcholinesterase
*BChE↓,
*chemoPv↑, Several mechanisms have suggested that CGAs may have a chemopreventive effect
*BioAv⇅, the absorption and bioavailability of CGAs are controversial due to the significant interindividual differences regarding their utilization, metabolism, and excretion found in scientific and clinical studies

6002- CGA,    Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials
- Review, Var, NA - Review, Diabetic, NA - Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms

6035- CGA,    Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial
- Trial, Nor, NA
*Dose↝, ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks.
*cognitive↑, Continuous intake of CGAs appears to improve attention and executive function among cognitive functions in MCI.
*Risk↓, Coffee intake has protective effects against some diseases, including type 2 diabetes mellitus, Alzheimer’s disease, and Parkinson’s disease [2–4].
*AChE↓, In a mouse model of scopolamine-induced cognitive impairment, administration of 5-CQA, the main component of CGAs, suppressed hippocampal acetylcholinesterase activity and reduced oxidative stress [14].
*ROS↓,

6033- CGA,  CA,    Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer's disease and some pro-oxidant induced oxidative stress in rats' brain-in vitro
- in-vivo, AD, NA
*AChE↓, caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner;
*BChE↓,
*eff↑, however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid
*eff↑, Combination of the phenolic acids inhibited AChE and BChE activities antagonistically.
*neuroP↑, phenolic acids exert their neuroprotective properties is by inhibiting AChE and BChE activities as well as preventing oxidative stress-induced neurodegeneration.

6032- CGA,    Protective Effects of Chlorogenic Acid Against Amyloid-Beta-Induced Oxidative Stress and Ion Transport Dysfunction in SH-SY5Y Cells
- in-vitro, AD, NA
*CRM↑, Chlorogenic acid (CGA) acts as a caloric restriction mimetic
*neuroP↑, CGA exerted neuroprotective effects against Aβ1-42-induced oxidative stress and impaired ion transporter and acetylcholinesterase activities, serving as a promising therapeutic candidate for neurodegenerative diseases, such as Alzheimer's disease.
*AChE↓,


Showing Research Papers: 1 to 50 of 153
Page 1 of 4 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 153

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   mitResp↓, 1,   MMP↓, 1,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 1,   Glycolysis↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 2,   Bak↓, 1,   BAX↑, 1,   Bax:Bcl2↑, 2,   Bcl-2↓, 2,   Bcl-2↑, 1,   BID↑, 1,   Casp↑, 1,   Casp1↑, 1,   Casp3↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 2,   Fas↑, 1,   p‑p38↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP70/HSPA5↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,   p‑P53↑, 1,   PARP↑, 2,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 3,  

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

EMT↝, 1,   p‑ERK↓, 1,   FGF↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   mTOR↓, 2,   PI3K↓, 2,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

5LO↓, 1,   CEA↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   TIMP2↑, 1,   TumCP↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,   EGFR↑, 1,   Hif1a↓, 2,   VEGF↓, 3,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   NF-kB↓, 1,   NF-kB↑, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 3,   Dose↝, 3,   eff↑, 2,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3,   AntiTum↑, 1,   OS↑, 1,  
Total Targets: 82

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 3,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 3,   antiOx↑, 21,   Catalase↑, 12,   Ferroptosis↓, 1,   GPx↑, 7,   GPx4↑, 1,   GSH↑, 11,   GSR↑, 2,   GSTs↑, 2,   HO-1↑, 9,   Keap1↑, 1,   lipid-P↓, 16,   MDA↓, 8,   NQO1↑, 3,   NRF2↑, 13,   RNS↓, 1,   ROS↓, 30,   SOD↑, 14,   TAC↑, 2,   TBARS↓, 1,   uricA↓, 1,   VitC↑, 1,   VitE↑, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 3,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 3,   MMP↑, 1,   mtDam↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACC↑, 1,   ALAT↓, 1,   ALAT∅, 1,   AMPK↑, 1,   p‑CREB↑, 1,   CRM↑, 1,   glucose↓, 2,   GlucoseCon↑, 2,   LDH↓, 1,   LDL↓, 3,   NADPH↑, 1,   PFK↓, 1,   PPARα↑, 2,   PPARα↝, 1,   PPARγ↑, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Akt↑, 2,   Apoptosis↓, 2,   BAX↓, 1,   Bcl-2↓, 1,   Bcl-2↑, 2,   Casp↓, 1,   Casp3↓, 3,   Cyt‑c↓, 1,   Ferroptosis↓, 1,   iNOS↓, 6,   JNK↓, 1,   MAPK↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

TRPV3↑, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach?, 1,   Ach↑, 5,   other?, 1,   other↓, 7,   other↑, 1,   other↝, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSPs↝, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

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

Choline↑, 1,   GSK‐3β↓, 4,   GSK‐3β↑, 1,   IGF-1↑, 1,   Nestin↑, 1,   NOTCH1↑, 1,   PI3K↓, 1,   PI3K↑, 3,   SOX2↑, 1,   TRPM7↓, 1,  

Migration(tgid=13) ⓘ

5LO↓, 4,   AntiAg↑, 2,   APP↓, 1,   Ca+2?, 1,   Ca+2↓, 1,   Ca+2↑, 1,   CD31↑, 1,   Ki-67↑, 1,   MMP13↓, 1,   N-cadherin↑, 1,   PKCδ↑, 1,   TRPC1↓, 1,   Tyro3↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

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

Barriers & Transport(tgid=15) ⓘ

BBB↑, 10,   BBB↝, 1,   GastroP↑, 2,   GLUT3↑, 1,   GLUT4↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CB2 / CNR2↑, 2,   CD4+↑, 1,   COX1↓, 1,   COX2↓, 9,   CRP↓, 1,   IL1β↓, 9,   IL6↓, 6,   IL6↑, 1,   Imm↑, 2,   Inflam↓, 24,   Inflam↑, 2,   MCP1↓, 1,   NF-kB↓, 10,   NF-kB↑, 1,   PGE2↓, 2,   TLR4↓, 3,   TNF-α↓, 14,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↑, 2,   AChE↓, 52,   BChE?, 1,   BChE↓, 16,   BDNF↓, 1,   BDNF↑, 5,   ChAT↑, 4,   GABA↑, 1,   MAOA↓, 5,   NGF↑, 1,   tau↓, 5,   p‑tau↓, 3,   TrkB↑, 3,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 17,   BACE↓, 6,   MAOB↓, 4,   NLRP3↓, 1,   PP2A↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CYP19↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 3,   BioAv↑, 6,   BioAv⇅, 1,   BioAv↝, 4,   Dose↑, 2,   Dose↝, 5,   eff↑, 14,   Half-Life↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   ALAT∅, 1,   ALP↓, 1,   AST↓, 2,   AST∅, 1,   BP↓, 2,   creat↓, 1,   CRP↓, 1,   GutMicro↑, 2,   IL6↓, 6,   IL6↑, 1,   Ki-67↑, 1,   LDH↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 5,   cardioP↑, 10,   chemoPv↑, 2,   cognitive↑, 21,   hepatoP↑, 4,   memory↑, 20,   Mood↑, 2,   motorD↑, 4,   neuroP↑, 32,   NP/CIPN↓, 1,   Obesity↓, 2,   Pain↓, 2,   RenoP↑, 2,   Risk↓, 1,   Sleep↑, 2,   Strength↑, 1,   toxicity↓, 8,   toxicity∅, 1,   Weight↓, 1,   Wound Healing↑, 2,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 2,   Bacteria↓, 4,   CD8+↑, 1,   Diar↓, 1,   Sepsis↓, 1,  
Total Targets: 183

Scientific Paper Hit Count for: AChE, acetylcholinesterase
17 Curcumin
11 Chlorogenic acid
10 Huperzine A/Huperzia serrata
10 Rosmarinic acid
9 Crocetin
7 Berberine
7 Ferulic acid
7 Thymoquinone
6 Quercetin
6 Moringa oleifera
5 Caffeic acid
5 Carvacrol
5 Salvia officinalis
4 EGCG (Epigallocatechin Gallate)
4 α-Bisabolol / Chamomile oil
4 Selenium NanoParticles
4 Piperine
4 Shankhpushpi
4 Silymarin (Milk Thistle) silibinin
3 Aromatherapy
3 Boswellia (frankincense)
3 Centella asiatica / Gotu kola → asiaticoside
3 Galantamine
3 Resveratrol
3 Naringin
2 Alpha-Lipoic-Acid
2 Apigenin (mainly Parsley)
2 Ashwagandha(Withaferin A)
2 Luteolin
2 Beta-Caryophyllene
2 beta-carotene(VitA)
2 Bacopa monnieri
2 Boron
2 Rutin
2 D-limonene
2 Geraniol
2 Mushroom Lion’s Mane
1 DTS(dibenzyl trisulphide) from Anamu
1 Astaxanthin
1 Biochanin A
1 xanthohumol
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Chrysin
1 Cinnamon
1 Vitamin E
1 Rivastigmine
1 Ginger/6-Shogaol/Gingerol
1 Capsaicin
1 Ellagic acid
1 Emodin
1 Ginkgo biloba
1 Honokiol
1 MCToil
1 Magnetic Field Rotating
1 Magnetic Fields
1 Methylsulfonylmethane
1 Nimbolide
1 Propolis -bee glue
1 Carnosic acid
1 Caffeine
1 Selenium
1 Sesame seeds and Oil
1 Chemotherapy
1 Safflower yellow
1 Turmerones
1 Thymol-Thymus vulgaris
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#:1329  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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