BACE/β-secretase Cancer Research Results

BACE/β-secretase, β-site APP-cleaving enzyme: Click to Expand ⟱
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BACE stands for β-site APP-cleaving enzyme, also known as β-secretase. It plays a central role in the pathogenesis of Alzheimer’s disease by initiating the production of amyloid-β (Aβ) peptides, the primary components of amyloid plaques found in the brains of individuals with AD.
-inhibiting BACE1 reduces Aβ production.

BACE1 - Beta-Site APP Cleaving Enzyme 1 / β-Secretase 1

Abbreviation: BACE1, β-secretase, β-secretase 1

Type: Aspartyl protease / amyloidogenic APP-processing enzyme

Function: BACE1 is a membrane-associated aspartyl protease that performs the initial β-secretase cleavage of amyloid precursor protein (APP). This cleavage generates soluble APPβ and the membrane-bound C99 fragment, which is subsequently cleaved by γ-secretase to produce amyloid-β peptides including Aβ40 and Aβ42.

Alzheimer's Disease: ↑ Increased BACE1 expression or enzymatic activity promotes amyloidogenic APP processing and increases amyloid-β production. Elevated BACE1 activity has been reported in Alzheimer's disease and contributes to Aβ accumulation, plaque formation, synaptic dysfunction, and disease progression. BACE1 inhibition reduces Aβ production, although clinical BACE1 inhibitors have been limited by adverse effects related to the enzyme's normal physiological functions.
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/PTGS2↓, ,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/β-secretase↓,
*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.

3864- ACNs,    Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain
*Aβ↓,
*ROS↓,
*cognitive↑, Mulberries are a rich source of ANTs that induce antioxidant enzymes and promote cognition
*APP↓, In the cerebral cortex, blackcurrant and bilberry extract reduced APP levels in AD mouse models, but changes in the expression or phosphorylation of tau-protein were not observed
*BBB↑, ANTs cross the blood-brain barrier and protect brain tissue from Abeta toxicity
*Ca+2↓, Aronia melanocarpa. ANTs of this plant decrease intracellular calcium and ROS but increase ATP and mitochondrial potential.
*ATP↑,
*BACE/β-secretase↓, An-NPs also attenuate the protein expression of BACE-1 neuroinflammatory markers, such as phosphonuclear factor kB (p-NF-kB), tumor-necrosis factor (TNF-α), and inducible nitric oxide synthase (iNOS),
*p‑NF-kB↓,
*TNF-α↓,
*iNOS↓,

7396- Amla,    Enhancing cognitive memory function using Phyllanthus emblica polysaccharides via modulating autophagy and reshaping the gut microbiota
- in-vivo, AD, NA
*Inflam↓, Phyllanthus emblica polysaccharides (PEP) exhibit anti-inflammatory, antioxidant, and gut microbiota-modulating properties in colitis and obese mice.
*antiOx↓,
*GutMicro↑,
*cognitive↑, In vivo results showed that PEP administration significantly alleviated cognitive decline by reducing neuroinflammatory cytokines (TNF-α, IL-6, and IL-1β) and MDA levels while increasing anti-inflammatory factors (IL-4 and IL-10) and antioxidants (S
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓,
*IL4↑,
*IL10↑,
*TAC↑,
*ATG5↑, Mechanistically, PEP upregulated autophagy-related proteins (Atg5, Beclin1, and LC3B) and LRP1 expression while downregulating AD-related proteins (BACE1, APP, Aβ, and phospho-TauSer404)
*Beclin-1↑,
*LC3B↑,
*LRP1↑,
*BACE/β-secretase↓,
*APP↓,
*Aβ↓,
*tau↓,

7839- AO,  ISQ,    The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model
- in-vivo, AD, NA - in-vivo, Obesity, NA
*Dose↝, For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally
*Obesity↓, Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice
*Leptin↓, decrease in leptin and an increase in adiponectin levels compared with the control group
*adiP↑,
*hepatoP↑, EAO- and isoquercitrin-administered groups attenuated liver damage
*PSEN1/PS1↓, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice.
*PSEN2/PS-2↓,
*BACE/β-secretase↓,
*eff↑, EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

3884- Api,    Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model
- in-vivo, AD, NA
*memory↑, Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice.
*Aβ↓, Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels.
*BACE/β-secretase↓, we observed BACE1 level reduction treated with apigenin.
*antiOx↑, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase.
*BDNF↑, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex.
*p‑CREB↑, After long-term apigenin treatment, coupled with the elevation of BDNF level, enhanced phosphorylated ERK1/2 and CREB expression were detected in the cerebral cortex
*p‑ERK↑,
*ROS↓, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase (SOD) and GSH-Px.
*SOD↑,
*GPx↑,
*neuroP↑, observations are correlated with a prospective neuroprotective, anti-amyloidogenic and neurotrophic effects in AD deficits.

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/β-secretase↓, 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.

3671- Ash,    Withania somnifera showed neuroprotective effect and increase longevity in Drosophila Alzheimer’s disease model
- in-vivo, AD, NA
*OS↑, The untreated Act5C-Aβ42 flies live for approximately 16 days, while the Act5C-Aβ42 treated with Ashwagandha showed improvement in their lifespan living up to 29 days
*BACE/β-secretase↓, shwagandha was also shown to down-regulate beta-secretase 1 (BACE1) a

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/β-secretase↓,
*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

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/β-secretase↓, 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.

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/β-secretase↓,
*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

4300- BBR,    Effect of berberine on cognitive function and β-amyloid precursor protein in Alzheimer’s disease models: a systematic review and meta-analysis
- Review, AD, NA
*APP↓, Berberine can regulate APP expression and improve cognitive function in animal models of AD,
*cognitive↑,
*Aβ↓, Berberine is involved in regulating APP modification, which may inhibit Aβ production through BACE1 inhibition and regulation of γ-secretase substrates.
*BACE/β-secretase↓,
*tau?, berberine may be a good multi-targeted drug that can modulate AD related substances tau, PP-2A, Aβ, APP, or BACE-2.

5631- BCA,    Perspectives Regarding the Role of Biochanin A in Humans
- Review, Var, NA - Review, AD, NA
*BioAv↓, Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption
*Inflam↓, various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects.
AntiCan↑,
*neuroP↑, many studies have focused on the effect of BCA on neurodegenerative diseases, especially PD and AD
chemoPv↑, BCA Has Chemopreventive Activity Against Various Cancers
Dose↝, BCA is metabolized in the gut to GEN or formononetin, which is converted to daidzein and then to equol (Knight and Eden, 1996).
*SOD↑, BCA also has a gastroprotective effect through the enhancement of cellular metabolic cycles, as evidenced by increases in superoxide dismutase (SOD) and nitric oxide (NO) activity, decreases in the malondialdehyde (MDA) and Bax levels, and increases
*MDA↓,
*BAX↓,
*HSP70/HSPA5↑, and increases in Hsp70 expression
*AntiDiabetic↑, BCA is well known for its antidiabetic and hypolipidemic effects.
*Insulin↑, BCA increases the circulating insulin levels and improves insulin sensitivity, leading to body weight control, an increase in liver glycogen, and a decrease in plasma glucose
*TNF-α↓, BCA inhibits the production of inflammatory mediators, such as TNF-α, interleukin-1β (IL-1β), IL-6, iNOS, COX-2, MMP-9, and NO, in various inflammatory responses
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2/PTGS2↓,
*MMP9↓,
*ROS↓, BCA scavenges ROS and increases SOD activity
*PGE2↓, BCA significantly reduces the synthesis of prostaglandin E2 and/or thromboxane B2 by inhibiting COX-2 expression
*BACE/β-secretase↓, BCA effectively inhibits the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
*BioAv↑, Various attempts have been made to improve the solubility and bioavailability of BCA, including the use of liposomes
P-gp/ABCB1⇅, Interestingly, BCA has been found to stimulate P-gp in some studies (An and Morris, 2010). Therefore, the effect of BCA on P-gp may be substrate dependent.

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/β-secretase↓, 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.

4082- betaCar,    Marginal vitamin A deficiency facilitates Alzheimer's pathogenesis
- Study, AD, NA
*cognitive↑, Vitamin A deficiency (VAD) has been shown to affect cognitive functions. VA supplementation improves cognitive deficits.
*BACE/β-secretase↓, We found that MVAD, mostly prenatal MVAD, promotes beta-site APP cleaving enzyme 1 (BACE1)-mediated Aβ production and neuritic plaque formation, and significantly exacerbates memory deficits in AD model mice
*memory↑, Supplementing a therapeutic dose of VA rescued the MVAD-induced memory deficits.

5688- BJ,    Brucea Javanica Oil Emulsion Injection inhibits proliferation of pancreatic cancer via regulating apoptosis-related genes
- vitro+vivo, PC, MIA PaCa-2
TumCG↓, In vitro experiments further revealed that BJOEI could suppress cell growth and invasion, arrest cells at the S stage, and cause cell apoptosis
TumCI↓,
TumCCA↑, BJOEI induced cell cycle arrest and cell apoptosis
Apoptosis↑,
BAX↑, BJOEI upregulated BAX and cleaved caspase3 expression and downregulated BCL2 expression
cl‑Casp3↑,
Bcl-2↓,
MMP2↓, expression of MMP2, PTGS2, BACE1, and TOP2A were downregulated.
BACE/β-secretase↓,
TOP2↓,

3693- BM,    Bacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action
- in-vivo, AD, NA
*cognitive↑, BM supplementation was able to improve cognitive functions, suppress Aβ formation by reducing BACE-1 activity
*Aβ↓,
*BACE/β-secretase↓,
*Inflam↓, Inflammatory and oxidative stress markers were attenuated in the brain regions of BM supplemented animals.
*ROS↓,
*antiOx↑, anti-inflammatory and anti-oxidant action

5663- BNL,    Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice
- in-vivo, AD, NA
*ZO-1↓, Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression
*cl‑Casp3↓, Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio
*Bax:Bcl2↓,
*MDA↓, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice
*Apoptosis↓,
*Aβ↓,
*BACE/β-secretase↓,
*cognitive↑,
*BioAv↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
memory↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
P-gp/ABCB1↓, This may be caused by a higher dose of BO inhibiting the action of the P-gp transporter in intestinal mucosa and CYP450 metabolism in the liver.
BioEnh↑,

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/PTGS2↓,
*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/β-secretase↓, 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/PTGS2↓,
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/PTGS2↓,
*TNF-α↓,
*IL6↑,
*MMP13↓,

7832- CA,  CGA,  MBS,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA
*BBB↑, both caffeic and chlorogenic acid could cross the BBB
*cognitive↑, caffeic acid (10−50 mg/kg/d, p.o.) improved the cognitive and memory impairments in Aβ25−35injected (i.c.v.) mice by the inhibition of oxidative stress
*memory↑,
*ROS↓,
*p‑tau↓, Aβ25−35-induced tau hyperphosphorylation was also suppressed by caffeic acid through reducing the calcium-dependent GSK-3β activation.
*GSK‐3β↓,
*MAPK↓, inhibited p38 MAPK activation to reduce neuroinflammation, suppressed p53 expression to downregulate caspase-3-mediated apoptosis, and decreased AChE activity.
*NeuroI↓,
*P53↓,
*Casp3↓,
*AChE↓,
*APP↓, by suppressing APP expression, β-secretase (BACE) activity, and GSK-3β activation, implying its neuroprotective activity under cerebral insulin resistance.
*BACE/β-secretase↓,
*neuroP↑,
*Dose↝, lowest effective dose of caffeic acid was 10 mg/kg in rats (Table 3), while its content range in the mung bean was 0.03−38.72 mg/100 g

7521- CA,    Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells
- in-vitro, AD, HT22
*neuroP↑, CA/CAPE significantly attenuated acrolein-induced neurotoxicity, ROS accumulation, and GSH depletion.
*ROS↓,
*GSH↑,
*Akt↑, CA/CAPE showed protective effects against acrolein by modulating MAPKs and Akt/GSK3β signaling pathways.
*GSK‐3β↑,
*BACE/β-secretase↓, CA/CAPE restored the changes of β-secretase (BACE-1) and/or activation of α-secretase (ADAM-10) induced by acrolein.
*p38↓, CA/CAPE inhibited the activation of p38 and JNK1 while promoted the activation of ERK and Akt/GSK3 caused by acrolein
*RAGE↓, In our study, ADAM-10 and LR-11 were decreased while BACE-1 and RAGE were increased after the exposure of acrolein for 24 h (Fig. 3). Of interest, these changes were almost restored by both CA and CAPE
*ADAM10↑,

7516- CA,    Caffeic Acid, a Polyphenolic Micronutrient Rescues Mice Brains against Aβ-Induced Neurodegeneration and Memory Impairment
- in-vivo, AD, NA
*neuroP↑, It has been reported that the polyphenolic compound caffeic acid possesses strong neuroprotective and antioxidant effects.
*antiOx↑,
*memory↑, The behavioral results indicated that caffeic acid administration improved spatial learning, memory, and cognitive abilities in AD mice.
*Learn↑,
*cognitive↑,
*ROS↓, ROS and LPO were markedly reduced in the caffeic acid-treated mice
*lipid-P↓,
*NRF2↑, expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were regulated with the administration of caffeic acid
*HO-1↑,
*Aβ↓, caffeic acid treatment also decreased Aβ and BACE-1 expression in the Aβ-induced AD mice model.
*BACE/β-secretase↓,

5952- Cela,    Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
- in-vivo, AD, NA
*memory↑, pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress.
*Inflam↓,
*ROS↓,
*ER Stress↓, celastrol suppressed AD progression by targeting ER stress
*neuroP↑, celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.
*Dose↝, administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. (1, 3, 6 mg/kg/day) for 2 days
*MDA↓, AD mouse group treated with celastrol showed lower levels of protein carbonyl and MDA and higher activity of CAT and SOD compared to the AD group
*SOD↑,
*Catalase↑,
*Aβ↓, Research has shown that celastrol can reduce cell death and Aβ production in cell experiments
BACE/β-secretase↓, celastrol treatment significantly restored the expression of BACE1, LRP1, NEP, and RAGE in the brain
LRP1↑, Activation of LRP1 by celastrol may lead to the attenuation of AD symptoms.
RAGE↓,

6624- Cic,    Chicoric acid supplementation ameliorates cognitive impairment induced by oxidative stress via promotion of antioxidant defense system
- in-vivo, AD, NA - in-vivo, Park, NA
*neuroP↑, Chicoric acid attenuated neuron damage in d-gal-treated mice as revealed through histological examination in the hippocampus region of the mouse brain.
*TNF-α↓, The levels of inflammatory mediators, such as TNF-α and IL-1β, as well as malondialdehyde levels, were markedly reduced after chicoric acid treatment.
*IL1β↓,
*MDA↓,
*Catalase↑, activity of CAT and the level of GSH were significantly elevated in serum by chicoric acid
*GSH↑,
*NRF2↑, chicoric acid treatment noticeably activated the Nrf2 antioxidative defense system
*mtDam↓, reversing mitochondrial dysfunction, decreasing inflammation, and neuron apoptosis caused by oxidative stress.
*Inflam↓,
*Apoptosis↓,
*ROS↓, chicoric acid significantly quenched intracellular ROS to the normal level
*cognitive↑, suggested that chicoric acid supplementation ameliorated cognitive impairment induced by d-gal and SH-SY5Y cell apoptosis induced by H2O2
*Aβ↓, chicoric acid inhibited d-gal-induced Aβ1-42 accumulation in hippocampus of mice brain.
*BDNF∅, suggesting chicoric acid treatment did not restore the expression of BDNF in the hippocampus of aging mice.
*APP↓, chicoric acid treatment markedly decreased the expression of APP and BACE1 in the whole brain, which partly explains the inhibition by chicoric acid of Aβ1-42 accumulation in the cortex and hippocampus.
*BACE/β-secretase↓,

6625- Cic,  Ech,    Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-κB
- in-vivo, NA, NA
*memory↑, CA prevented LPS-induced memory impairment and neuronal loss through behavioral tests and histological examination.
*Aβ↓, CA prevented LPS-induced increases in amyloid β (1-42 specific) (Aβ1-42) accumulation, levels of amyloid precursor protein, and neuronal β-secretase 1 (BACE1), as well as the equilibrium cholinergic system in mouse brain.
*BACE/β-secretase↓,
*MAPK↓, CA down-regulated LPS-induced glial overactivation by inhibiting the MAPK and NF-κB pathway
*NF-kB↓,
*NF-kB↓, CA reduced the levels of NF-κB transcriptionally regulated inflammatory mediators and cytokines such as iNOS, cyclooxygenase-2 (COX-2), IL-1β, and TNF-α in both mouse brain and BV2 microglial cells.
*iNOS↓,
*COX2/PTGS2↓,
*IL1β↓,
*TNF-α↓,
*BDNF∅, we found that BDNF, NGF, NT3, and NT4 mRNA expressions of neurotrophic factors exhibited no changes after CA treatment
*MMPs↓, CA also down-regulated the mRNA levels of MMPs in LPS-treated mice, which might provide another clue for the explanation of the anti-amyloidosis effects of CA (

3860- CUR,    Curcumin Ameliorates Memory Decline via Inhibiting BACE1 Expression and β-Amyloid Pathology in 5×FAD Transgenic Mice
- in-vivo, AD, NA
*Aβ↓, Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression
*BACE/β-secretase↓,
*memory↑, Curcumin Ameliorates Memory Decline

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/PTGS2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1/CCL2↓,
*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/β-secretase↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.

3756- EA,    Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
- Analysis, AD, NA
*AChE↓, Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM : All five compounds weakly inhibited BChE and BACE-1.
*BACE/β-secretase↓,
*MAOB↓, inhibited MAO-B by more than 50%.

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/β-secretase↓, 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↑,

3830- EMD,    Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, brain protection properties
*Aβ↓, Emodin suppresses Aβ deposition and tau phosphorylation.
*p‑tau↓,
*BACE/β-secretase↓, emodin downregulates the activity of β-site APP-cleaving enzyme 1 (BACE1) and increases protein phosphatase 2A levels

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/β-secretase↓, 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↓,

6826- EMD,    Exploring the therapeutic potential of natural compounds for Alzheimer's disease: Mechanisms of action and pharmacological properties
*AntiCan↑, Emodin has a wide range of pharmacological activities, including anticancer, hepatoprotective, anti-inflammatory, antioxidant, and antibacterial activities
*hepatoP↑,
*Inflam↓,
*antiOx↑,
*Bacteria↓,
*Aβ↓, Although Emodin did not reduce plasma homocysteine levels, it reduced Aβ and tau phosphorylation levels, decreased levels of β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and increased protein phosphatase 2 A (PP2A) activity.
*p‑tau↓,
*BACE/β-secretase↓,
*PP2A↑,

3782- FA,    Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer’s disease-like pathology through Akt-ERK crosstalk pathway in male rats
- in-vivo, AD, NA
*cognitive↑, Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA
*ERK↓, a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels
*p‑Akt↓,
*AChE↓, brain levels of AChE and BACE were substantially reduced in BPA + FA rats.
*BACE/β-secretase↓,
*neuroP↑, neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.
*ROS↓, FA was sufficient to trigger antioxidant capabilities and decrease intracellular reactive oxygen species (ROS
*MDA↓, BPA + FA revealed a substantial reduction in MDA levels compared to rats intoxicated with BPA
*GSH↑, BPA + FA revealed a significant increment of GSH associated with a significant decrease in GSSG
*GSSG↓,
*p‑tau↓, BPA + FA showed a significant decline in the brain level of pTau compared to intoxicated rats.
*lipid-P↓, inhibit lipid peroxidation
*Aβ↓, FA has significantly counteracted the deleterious effect of BPA by decreasing Aβ 1–42, as previously reported

7829- FA,  MBS,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA
*BioAv↑, Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is abundant in some cereal grains and shows relatively higher absorption in the gastrointestinal mucosa compared to other phenolic acids
*cognitive↓, oral administration of ferulic acid (200 mg/d plus 40 mg of Angelica archangelica extract) daily for 48 weeks improved the mild cognitive impairment in populations aged 65−85 years old.
*Dose↝, ferulic acid (200 mg/d plus 40 mg of Angelica archangelica extract) daily for 48 weeks
*neuroP↑, ferulic acid might possess great neuroprotective potential in the neurodegenerative diseases.
*Aβ↓, ferulic acid reduced Aβ plaque deposits via inhibiting β-secretase (BACE1) activity and cleavage, as well as enhancing α-secretase (ADAM10) activity and cleavage in APP/PS1 mice
*BACE/β-secretase↓,
*ADAM10↑,
*Ac-histone H3↑, ferulic acid improved the cholinergic deficits as indicated by the increased ACh level in the cortex of Aβ1−42 -injected (i.c.v.) mice after ferulic acid treatmen
*BloodF↑, rerulic acid improved the cerebral blood flow (CBF) and insulin resistance, which helped to reduce the progression of AD pathology
*IRes↑,
*memory↑, while ferulic acid treatment (20 mg/kg, p.o.) improved the capillary hypofunction and reduced the memory deficits of APP/PS1 mice.
*Dose↝, Notably, the effective doses of ferulic acid in rodents were 5.3−30 mg/kg when administered for more than 4 weeks, which could be achieved through daily intake of appropriate amount of mung bean

6923- Flav,    Flavonoids: an overview
- Review, Nor, NA
*antiOx↑, anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function.
AntiCan↑,
*cardioP↑, Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD.
*XO↓, They are also known to be potent inhibitors for several enzymes, such as xanthine oxidase (XO), cyclo-oxygenase (COX), lipoxygenase and phosphoinositide 3-kinase
*COX2/PTGS2↓,
*5LO↓,
*PI3K↓,
*AChE↓, A number of flavonoids have been reported for their anti-cholinesterase activity.
*Imm⇅, These effects indicate the immune-regulatory roles of flavonoids.
*BP↓, regular quercitin intake on blood pressure in overweight and obese patients with pre-hypertension and stage I hypertension was studied in seventy patients.
TumCCA↑, t pelingo juice induced cell accumulation in the G2/M phase of the cell cycle
*Aβ↓, certain flavonoids such as genistein, quercetin, taxifolin, kaemferol, luteolin, apigenin, daidzein, aminogeneistein, and α- and β-napthofalvone can affect Aβ production.
*BACE/β-secretase↓, direct inhibition of β active site cleavage enzyme-1 (BACE-1) activity
*NF-kB↓, inhibition of NF-κB activation by flavonoids
*ROS↓, flavones and catechins seem to be the most powerful flavonoids for protecting the body against reactive oxygen species.
*neuroP↑, like prevention of the neurodegeneration associated with AD and Parkinson's disease
*AntiAg↑, figure 3
*AntiThr↑,

7833- GA,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA
*neuroP↑, Gallic acid (3,4,5-trihydroxybenzoic acid) showed neuroprotective activity against AD in various roden
*Dose↝, gallic acid (20 or 30 mg/kg) improved the cognitive impairments no matter it was administrated from the early (4 months), middle (9 months) or late-stage (12 months) of AD pathology
*ADAM10↝, related mechanisms involved modulation of the activity of α-secretase (ADAM10) and βsecretase (BACE-1) to inhibit the amyloidogenic cleavage of APP, disruption of the salt bridge between Aβ to suppress its aggregatio
*BACE/β-secretase↓,
*cl‑APP↓,
*Aβ↓,
*Ca+2↓, improvement of synaptic plasticity, as well as inhibition of Ca2+ influx, oxidative stress, and neuroinflammation.
*ROS↓,
*NeuroI↓,

4302- Gins,    Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease
- Review, AD, NA
*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE/β-secretase↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

4003- Gins,    Neuroprotective Potentials of Panax Ginseng Against Alzheimer's Disease: A Review of Preclinical and Clinical Evidences
- Review, adrenal, NA
*neuroP↑, has neuroprotective effects against a series of pathological cascades in AD, including beta-amyloid formation, neuroinflammation, oxidative stress, and mitochondrial dysfunction.
*Inflam↓,
*ROS↓,
*BACE/β-secretase↓, Ginsenoside Re inhibits the activity of BACE1 by increasing PPARγ expression at the mRNA and protein levels in N2a/APP695 cells and thereby reduces the generation of Aβ1–40 and Aβ1–42
*PPARγ↑,
*Aβ↓, ginsenosides Rb1, Rd, Re, and Rg1 can inhibit Aβ aggregation to regulate the phosphorylation of tau protein in the prevention and treatment of AD.
*p‑tau↓, inhibiting tau phosphorylation
*NF-kB↓, Rd pretreatment at 10 mg/kg significantly suppresses the NF-κB pathway activity, reducing the generation of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)
*IL1β↓,
*IL6↓,
*TNF-α↓,
*ROS↓, Ginsenoside Rg1 can reduce the NADPH oxidase 2 (NOX2)–mediated ROS production and neuronal apoptosis
*CREB↓, Ginsenoside F1 can decrease phosphorylated cAMP-response element binding protein (CREB) and increase cortical BDNF levels in the hippocampus, reducing Aβ plaques and improving memory function of APP/PS1 double-transgenic AD mice
*BDNF↑,
*memory↑,

7482- H2,    Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA - Review, Sepsis, NA - Review, AD, NA
Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

3768- H2,    Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial
- Trial, AD, NA
*ROS↓, Investigation of oxidative stress markers such as reactive oxygen species and nitric oxide showed that their levels decreased post-treatment.
*NO↓,
*BACE/β-secretase↓, BACE-1), amyloid beta (Aβ), r (BDNF), (VEGF-A), T-tau, monocyte chemotactic protein-1 (MCP-1), and inflammatory cytokines (interleukin-6), showed that their cognitive condition significantly improved after treatment, in most cases.
*BDNF↑, see figure 5
*VEGF↑,
*p‑tau↓, t-tau and p-tau levels reduced dramatically in different ages within 4 weeks of treatment;
*MCP1/CCL2↓, MCP-1 (p < 0.001) (Figure 7A), IL-6 (p < 0.05) (Figure 7B), and VEGF-A (Figure 7C) levels significantly decreased
*IL6↓,
*cognitive↑, H2 gas inhalation may be a good candidate for improving AD with cognitive dysfunction
*toxicity∅, H2 gas inhalation treatment did not cause any adverse effects, indicating that it was safe.

3767- H2,    The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges
- Review, AD, NA
*Inflam↓, Hydrogen therapy AD: inflammation, energy regulation, prevents neuronal damage.
*neuroP↑,
*toxicity↓, Hydrogen therapy's low side effects make it a complement to AD treatment. Even at high concentrations, hydrogen gas is still non-toxic, and has been widely used in the diving field.
*antiOx↑, hydrogen’s role as a natural antioxidant,
*ROS↓, Hydrogen has been shown to mitigate the amount of ROS released from mitochondria, thereby reducing mitochondrial DNA peroxidation and inhibiting the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), caspase-1, and I
*NLRP3↓,
*IL1β↓,
*mtDam↓, curtail mitochondrial damage, thereby bolstering ATP synthesis and fortifying the electron transport chain within mitochondria
*ATP↑,
*AMPK↑, activating AMPK and amplifying the downstream antioxidant response of forkhead box O3a (FOXO3
*FOXO3↑,
*SOD1↑, It elevates the levels of intracellular antioxidant enzymes, notably superoxide dismutase 1 (SOD1) and catalase (CAT), thereby serving as a neuroprotective agent that diminishes the risk and progression of AD
*Catalase↑,
*NRF2↑, Hydrogen slows AD progression by activating the cellular endogenous antioxidant system Nrf2;
*NO↓, Reduced inflammatory markers such as ROS, Nitric oxide (NO) and Malondialdehyde (MDA)
*MDA↓,
*lipid-P↓, drinking HRW significantly reduced lipid peroxidation in the brain of SAMP8 mice.
*memory↑, HRW inhibited the decline of learning and memory impairment
*ER(estro)↓, Decreased hormone levels, estrogen receptor (ER) β, and BDNF expression improve cognitive function in female transgenic AD mice.
*BDNF↑, upsurge in BDNF levels, which further ameliorated the cognitive impairments observed in mice affected by sepsis.
*cognitive↑,
*APP↓, The expression of APP, BACE1, and SAPPβ was proficiently suppressed, thereby curtailing the overproduction of Aβ in Alzheimer's
*BACE/β-secretase↓,
*Aβ↓,
*BP∅, inhaling hydrogen gas has no effect on blood pressure and other blood parameters (such as pH, body temperature, etc.),
*BBB↑, efficiently crossing the blood-brain barrier to perform their functions.

7497- H2S,    Hydrogen sulfide improves spatial memory impairment and decreases production of Aβ in APP/PS1 transgenic mice
- in-vivo, AD, NA
*other↓, Previous research has demonstrated that production of neuronal hydrogen sulfide (H2S) is significantly decreased in patients with AD
*memory↑, After intraperitoneal (i.p.) administration of an H2S donor (NaHS) into APP/PS1 mice, application of exogenous H2S resulted in improved spatial learning and memory acquisition in APP/PS1 mice.
*BACE/β-secretase↓, H2S administration also led to significant decrease in extracellular levels of Aβ40 and Aβ42, the expression of BACE1 and PS1, and a significant increase of ADAM17 expression.
*ADAM17↑,

7500- H2S,    Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2
- in-vivo, AD, NA
*neuroP↑, Hydrogen sulfide (H2S) has been recognized as a cytoprotectant, which improves learning memory impairment and exerts antioxidant effects in neurodegenerative disorders, including AD.
*memory↑,
*CBS↑, intraperitoneal (i.p.) injection of NaHS improved learning memory deficits, decreased the number of senile plaques, Aβ1-40 and Aβ1-42 levels, suppressed neurons loss, together with up-regulated the levels of cystathionine-β-synthase (CBS) and 3MST
*3MST/MPST↑,
*APP↓, the protein levels of beta-amyloid precursor (APP) and beta-secretase 1 (BACE1) were dramatically restrained after administration of H2S
*BACE/β-secretase↓,
*NRF2↑, H2S exerted antioxidant effects via up-regulation nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and glutathione S-transferase (GST).
*HO-1↑,
*GSTs↑,
*Aβ↓, inhibition of Aβ production and activation of Nrf2/antioxidant response element (ARE) pathway.
*ARE↑,

7453- HNK,    Determination of Potential Lead Compound from Magnolia officinalis for Alzheimer's Disease through Pharmacokinetic Prediction, Molecular Docking, Dynamic Simulation, and Experimental Validation
- Study, AD, NA
*BACE/β-secretase↓, honokiol emerged as a lead structure for the inhibition of BACE1, AChE, QC, and GSK-3β in docking and molecular dynamics (MD) simulations.
*AChE↓,
*QPCT/QC↓,
*GSK‐3β↓,
*toxicity↓, honokiol acts as a multiple enzyme inhibitor with an excellent pharmacokinetic and safety profile which may provide inhibitory effects in broad-range areas including the overproduction, aggregation, and post-translational modification of Aβ

4211- Hup,    Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice
- in-vitro, NA, NA
*memory↑, Hup A (0.1, mg · kg−1 · d−1) improved both the abilities of object recognition and spatial memory in HFD-fed mice, but not in ob/ob mice.
*p‑Akt↑, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but not ob/ob mice.
*BACE/β-secretase↓, In addition, Hup A (0.3, mg · kg−1 · d−1) significantly decreased cortical β-secretase (BACE1) expression.
*cognitive↑, Hup A (0.1, mg · kg−1 · d−1) can effectively improve the cognitive functions, at least in diet-induced obese mice.

3803- Hup,    Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer’s Disease
- Review, AD, NA
*AChE↓, effects of this alkaloid have been attributed to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), acting as an acetylcholinesterase inhibitor (AChEI).
*neuroP↑, summarize the neuroprotective effects of HupA on AD,
*BBB↑, HupA is an unsaturated sesquiterpene alkaloid compound that effectively crosses the blood-brain barrier (BBB), acting as a mixed-competitive, reversible, and selective AChE inhibitor
*Half-Life↑, with a half-life of 5 h in the bloodstream, reaching a peak concentration at approximately 60 min in humans
*cognitive↑, hows evidence of improved cognition
*Dose↝, significant cognitive enhancement in patients receiving 0.4 mg of HupA twice a day.
*BACE/β-secretase↓, while downregulating the membrane translocation of BACE1
*IronCh↑, HupA might act directly as an Fe2+ chelator, reducing the capacity of IRP-1 to induce APP translation
*TfR1/CD71↓, HupA also downregulates TFR1 expression in mice in vivo, which reduces the uptake of transferrin-bound iron (TBI) in neurons
*ROS↓, HupA indirectly reduces ROS

7544- HYP,    Long-term oral administration of hyperoside ameliorates AD-related neuropathology and improves cognitive impairment in APP/PS1 transgenic mice
- in-vivo, AD, NA
*Learn↑, After 9 months of treatment, we found that hyperoside can improve spatial learning and memory in APP/PS1 transgenic mice, reduce amyloid plaque deposition and tau phosphorylation
*memory↑,
*Aβ↓,
*p‑tau↓,
*Inflam↓, attenuate neuroinflammation and oxidative stress in the brain of APP/PS1 mice.
*ROS↓,
*BACE/β-secretase↓, These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3β levels.
*GSK‐3β↓,

7917- IVT,    A review on the pharmacological effects of vitexin and isovitexin
- Review, Nor, NA - Review, AD, NA
*antiOx↑, anti-oxidant, anti-cancer, anti-inflammatory, anti-hyperalgesic, and neuroprotective effects.
*AntiCan↑,
*Inflam↓,
*neuroP↑,
*AChE↓, Anti-Alzheimer's disease Vitexin/isovitexin In vitro ChE enzyme assay Vitexin: IC 50 = 12.16 ± 3.58 (AChE) IC 50 = 6.73 ± 0.08 (BChE) IC 50 = 51.07 ± 3.31(BACE1) Isovitexin: IC 50 = 6.24 ± 1.15 (AChE) IC 50 = 6.48 ± 0.43 (BChE) IC 50 ≥ 100 (BA
*BChE↓,
*BACE/β-secretase↓,
*Stroke↓, Data showed that vitexin exhibits protective effect against cardiac ischemia/reperfusion (I/R) injury through inhibiting the I/R-induced decrease in coronary flow
*AntiAg↓, Vitexin-containing lime leaf significantly inhibited platelet aggregation in a concentration-dependent manner
*AntiDiabetic↑, Administered orally, vitexin and isovitexin significantly reduced postprandial blood glucose both in sucrose loaded normoglycemic mice and sucrose induced diabetic rat
*AGEs↓, vitexin and isovitexin, as AGE inhibitors,
*IL1β↓, inhibition in the pro-inflammatory cytokines such as IL-1β, IL6, IL-8, TNF-α,
*IL6↓,
*IL8↓,
*TNF-α↓,
*Obesity↓, Protective effects against obesity
*BioAv↝, Unusually, vitexin and isovitexin are poorly absorbed in the gastrointestinal tract [61]. They directly reached the colon where they were hydrolysed by the gut microflora through deglycosylation and ringopening of the heterocyclic C ring
*BioAv↓, oral bioavailability of vitexin was much low (approximately 5%

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE/β-secretase↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

3828- Lyco,    Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease
- in-vitro, AD, M146L
*ROS↓, Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins.
*PI3K↑,
*Akt↑,
*NRF2↓,
*antiOx↑,
*BACE/β-secretase↓, lycopene inhibited β -secretase (BACE) activity in M146L cells.
*MDA↓,

7824- MBS,  IVT,  VT,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA - Review, Stroke, NA - Review, Park, NA
*neuroP↑, it was speculated that vitexin, isovitexin, sinapic acid, and ferulic acid might be the major bioactive compounds for mung bean-mediated neuroprotection.
*Aβ↓, inhibition of β-amyloidogenesis, tau hyperphosphorylation, oxidative stress, and neuroinflammation, and promotion of autophagy and acetylcholinesterase enzyme activity.
*p‑tau↓,
*ROS↓,
*Inflam↓,
*AChE↓, vitexin significantly inhibited the activity of AChE in vitro, with an IC 50 of 12.16 μM.
*BBB↑, Notably, considerable levels of vitexin and isovitexin were detected in the brain, indicating their ability to cross the blood brain barrier (BBB)
*memory↑, Another study showed that mung bean sprout possessed anti-Alzheimer potential as evidenced by the improved short-term and long-term memory as well as inhibited AChE activity and oxidative stress after administering mung bean sprout for 15 days in mic
*hepatoP↑, That is, except for neuroprotection, mung bean can also provide several other health benefits, such as hepatoprotection, immunomodulation, antihyperglycemia, antihyperlipidemia, antihypertension, and anticancer
*Imm↑,
*hyperG↓,
*AntiCan↑,
*eff↑, neuroprotective potential of seed coat extract might be much stronger than that of cotyledon extract.
*Stroke↓, Vitexin showed great activities in improving CNS-related diseases, including AD, ischemic stroke, and Parkinson’s disease.
*BACE/β-secretase↓, vitexin suppressed the production of Aβ through downregulating the activity of β-secretase (BACE-1) with an IC 50 of 51.07 μM in vitro
*PI3K↓, Isovitexin was found to inhibit the activation of the PI3K/AKT/mTOR pathway, which might explain the molecular targets for isovitexin.
*Akt↓,
*mTOR↓,
*Dose↓, At the fifth day of sprouting, contents of vitexin and isovitexin decreased by 3.7 and 9.3 times, respectively


Showing Research Papers: 1 to 50 of 72
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 72

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

CD47↓, 1,   miR-124-3p↓, 1,   PFS↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

MFN2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

PGC-1α↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

SCD1↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 4,   p‑Akt↓, 1,   Apoptosis↑, 5,   Bak↓, 1,   BAX↑, 3,   Bcl-2↓, 2,   Bcl-2↑, 1,   BID↑, 1,   Casp1↑, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   cl‑Casp3⇅, 1,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 2,   Fas↑, 1,   IAP2/BIRC3↓, 1,   MAPK↝, 1,   p38↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

EZH2↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK4↓, 1,   P21↑, 1,   TumCCA↑, 5,  

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

FGF↓, 1,   GSK‐3β↓, 1,   mTOR↓, 1,   mTOR↝, 1,   PI3K↓, 2,   TOP2↓, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

CEA↓, 1,   E-cadherin↓, 1,   LRP1↑, 1,   MALAT1↓, 1,   MMP2↓, 2,   MMP9↓, 1,   MMPs↓, 1,   RAGE↓, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

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

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,   P-gp/ABCB1⇅, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2,   NF-kB↑, 1,   NK cell↑, 1,  

Protein Aggregation(tgid=19) ⓘ

BACE/β-secretase↓, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioEnh↑, 1,   ChemoSen↑, 2,   Dose↝, 4,   eff↑, 4,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   EZH2↓, 1,   HER2/EBBR2↓, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 3,   chemoP↑, 1,   chemoPv↑, 1,   memory↑, 1,   NP/CIPN↓, 1,   QoL↑, 1,   radioP↑, 1,   TumVol↓, 1,  

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,  
Total Targets: 90

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

3MST/MPST↑, 1,   AntiBio↑, 3,   CBS↑, 1,   compII↑, 1,   IRes↑, 1,   Learn↑, 2,   NeuroI↓, 2,   PSEN1/PS1↓, 1,   PSEN2/PS-2↓, 1,   QPCT/QC↓, 1,   Stroke↓, 3,   TRPA1↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 2,   antiOx↑, 17,   ARE↑, 1,   Catalase↑, 7,   GPx↑, 5,   GSH↑, 6,   GSSG↓, 1,   GSTs↑, 1,   HNE↓, 1,   HO-1↑, 8,   hyperG↓, 1,   Keap1↑, 1,   lipid-P↓, 8,   MDA↓, 12,   MPO↓, 2,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 11,   ROS↓, 31,   SOD↑, 12,   SOD1↑, 1,   TAC↑, 2,   TBARS↓, 1,   uricA↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 5,   compIII↑, 1,   Insulin↑, 1,   MMP↑, 2,   mtDam↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Ac-histone H3↑, 1,   adiP↑, 1,   ALAT↓, 1,   AMPK↑, 2,   CREB↓, 1,   CREB↑, 3,   p‑CREB↑, 1,   LDL↓, 3,   NADPH↓, 1,   NADPH↑, 1,   PPARγ↓, 2,   PPARγ↑, 2,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Akt↑, 5,   p‑Akt↓, 1,   p‑Akt↑, 1,   Apoptosis↓, 3,   BAX↓, 2,   Bax:Bcl2↓, 2,   Bcl-2↑, 1,   Casp12↓, 1,   Casp3↓, 3,   cl‑Casp3↓, 1,   Casp9↑, 1,   Cyt‑c↓, 1,   GranB/GZMB↓, 1,   iNOS↓, 6,   p‑JNK↓, 1,   MAPK↓, 3,   MAPK↑, 1,   p38↓, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 1,   AntiThr↑, 1,   other↓, 6,   other↑, 1,   other↝, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   p‑eIF2α↓, 1,   ER Stress↓, 2,   GRP78/BiP↓, 1,   GRP78/BiP↑, 1,   HSP70/HSPA5↑, 1,   UPR↑, 1,   XBP-1↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↓, 1,   Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B↑, 1,   LC3II↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↓, 1,  

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

ERK↓, 1,   ERK↑, 1,   p‑ERK↑, 1,   FOXO3↑, 1,   GSK‐3β↓, 7,   GSK‐3β↑, 1,   mTOR↓, 3,   PI3K↓, 3,   PI3K↑, 3,  

Migration(tgid=13) ⓘ

5LO↓, 1,   AntiAg↓, 1,   AntiAg↑, 1,   APP↓, 10,   cl‑APP↓, 1,   Ca+2↓, 2,   CDK5↓, 1,   LRP1↑, 1,   MMP13↓, 1,   MMP9↓, 1,   MMPs↓, 1,   PKA↑, 1,   PKCδ↑, 1,   RAGE↓, 1,   TGF-β↑, 1,   TXNIP↓, 1,   ZO-1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,   NO↓, 3,   VEGF↑, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 8,   GastroP↑, 1,   IBI↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 2,   COX2/PTGS2↓, 6,   IFN-γ↓, 1,   IL10↑, 3,   IL17↓, 1,   IL1β↓, 13,   IL23↓, 1,   IL33↓, 1,   IL4↓, 1,   IL4↑, 1,   IL6↓, 8,   IL6↑, 1,   IL8↓, 2,   Imm↑, 3,   Imm⇅, 1,   Inflam?, 1,   Inflam↓, 18,   Inflam↑, 1,   LPS↓, 1,   MCP1/CCL2↓, 2,   NF-kB↓, 11,   p‑NF-kB↓, 1,   PGE2↓, 2,   TLR3↓, 1,   TNF-α↓, 14,  

Cellular Microenvironment(tgid=17) ⓘ

ADAM17↑, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 18,   ADAM10↑, 3,   ADAM10↝, 1,   BChE↓, 5,   BDNF↑, 6,   BDNF∅, 2,   ChAT↑, 1,   MAOA↓, 2,   tau?, 1,   tau↓, 4,   p‑tau↓, 13,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,   Aβ↓, 32,   BACE/β-secretase↓, 48,   IDE↑, 1,   MAOB↓, 2,   NLRP3↓, 4,   PP2A↑, 2,   XO↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CYP19↓, 1,   ER(estro)↓, 1,   Leptin↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 4,   BioAv↑, 10,   BioAv↝, 4,   Dose↓, 1,   Dose↝, 9,   eff↑, 9,   Half-Life↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 2,   BloodF↑, 2,   BP↓, 1,   BP∅, 1,   creat↓, 2,   GutMicro↑, 2,   IL6↓, 8,   IL6↑, 1,   RAGE↓, 1,   Urea↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   AntiCan↑, 3,   AntiDiabetic↑, 3,   antiPs↑, 1,   cardioP↑, 6,   cognitive↓, 1,   cognitive↑, 19,   hepatoP↑, 7,   memory↑, 24,   Mood↑, 1,   motorD↑, 2,   neuroP↑, 30,   Obesity↓, 4,   OS↑, 2,   Pain↓, 1,   RenoP↑, 3,   toxicity↓, 5,   toxicity∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 2,   AntiViral↑, 1,   Bacteria↓, 2,   CD8+↑, 1,   Sepsis↓, 1,  
Total Targets: 219

Scientific Paper Hit Count for: BACE/β-secretase, β-site APP-cleaving enzyme
4 Mung Bean Sprouts
3 Berberine
3 Curcumin
3 Huperzine A/Huperzia serrata
3 Caffeic acid
3 Emodin
3 Hydrogen Gas
3 Vitexin
3 Resveratrol
2 EGCG (Epigallocatechin Gallate)
2 Biochanin A
2 Cichoric acid / Chicoric acid
2 Ferulic acid
2 Ginseng
2 hydrogen sulfide
2 Isovitexin
2 Moringa oleifera
2 Quercetin
2 Sulforaphane (mainly Broccoli)
2 Urolithin
2 Vitamin B3,Niacin
1 1,8-Cineole
1 Anthocyanins
1 Phyllanthus emblica/Emblica officinalis/Amla / Indian Gooseberry
1 Acer okamotoanum
1 isoquercitrin
1 Apigenin (mainly Parsley)
1 Aromatherapy
1 Ashwagandha(Withaferin A)
1 Astaxanthin
1 beta-carotene(VitA)
1 Brucea javanica
1 Bacopa monnieri
1 borneol
1 α-Bisabolol / Chamomile oil
1 Chlorogenic acid
1 Celastrol
1 Echinacea
1 Ellagic acid
1 flavonoids
1 Gallic acid
1 Honokiol
1 Hyperoside
1 Luteolin
1 Lycopene
1 Magnetic Fields
1 Mushroom Lion’s Mane
1 Thymoquinone
1 Vanillic Acid
1 Vitamin A, Retinoic Acid
1 Vitamin B1/Thiamine
1 Vitamin B12
1 Folic Acid, Vit B9
1 Vitamin D3
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#:1349  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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