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PubMed: 29179999

Title
Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer's disease.
Journal
Pharmacological research
Volume
129
Issue
None
Pages
262-273
Date
2018-03-01
Authors
Efferth T | Fischer N | Seo EJ

Evidence 2d231c2ec0
JSON

Moreover,it reveals promising anti-inflammatory actions through suppress-ing the activation of NF-B [238–240].

a(CHEBI:"(+)-artemisinin") decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

a(CHEBI:"(+)-artemisinin") decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence ad2e280756
JSON

The expression of A was lowered by artemisinin through inhibition of the activity of NALP3 inflammasome in APPswe/PS1E9 transgenic mice [241].

a(CHEBI:"(+)-artemisinin") decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"(+)-artemisinin") decreases bp(GO:"NLRP3 inflammasome complex assembly") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence ed9564e074
JSON

The mitochondrial membrane potential, ROS and NO levels were down-regulated by 1,8-cineole in A 25-35-stimulated cells [250].

a(CHEBI:"1,8-cineole") decreases a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"1,8-cineole") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence e29b75b023
JSON

The expression of pro-inflammatory cytokines such as TNF-, IL-1 and IL-6 were significantly reduced by treatment of 1,8-cineole in A 25-35-induced cells [250].

a(CHEBI:"1,8-cineole") decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"1,8-cineole") decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"1,8-cineole") decreases p(HGNC:IL6) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence e8cbf8f866
JSON

Further-more, the expression of NOS-2, COX2 and NF-B was reduced by1,8-cineole [250].

a(CHEBI:"1,8-cineole") decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:

a(CHEBI:"1,8-cineole") decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

a(CHEBI:"1,8-cineole") decreases p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:

Evidence fd54e77d1e
JSON

It considerably decreased A 1-42-stimulated memory disorders in mice [128].

a(CHEBI:"N(5)-ethyl-L-glutamine") increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence f465e0e23e
JSON

Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128].

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence d37faf5f17
JSON

Besides, extracellular signal-regulated kinase (ERK), p38 MAPK and NF-B pathway were disrupted byL-theanine [128].

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 5b31fa7f01
JSON

It has antiox-idant effects via the interference of reactive components and ROS by redox cycling of quinine, and subsequently generating hydroquinone [209].

a(CHEBI:"alpha-tocopherol") decreases a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:

Evidence 86a01eb22a
JSON

Reduction of A expression and cytotoxic-ity stimulated by A in neuroblastoma cells and the inhibition of inflammatory cytokines, ROS and NO in microglial cells were detected upon treatment with -tocopherol [210].

a(CHEBI:"alpha-tocopherol") decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"alpha-tocopherol") decreases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"alpha-tocopherol") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 4036caa9dc
JSON

Oxidative stress and A expression were suppressed with -tocopherol in mouse model.

a(CHEBI:"alpha-tocopherol") decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

a(CHEBI:"alpha-tocopherol") decreases path(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:

Evidence 6df3bc0175
JSON

Memory defi-ciencies were improved by -tocopherol in transgenic mice.

a(CHEBI:"alpha-tocopherol") increases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence bebd9c97ef
JSON

Furthermore, it disrupted the activity of NF-B, and thus, caused the suppression of NO synthase and inflammatory regulators such as IL-6 and IL-1, and the reduction of microglial activation [37]

a(CHEBI:"alpha-tocopherol") decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:

a(CHEBI:"alpha-tocopherol") decreases bp(GO:"microglial cell activation") View Subject | View Object

Appears in Networks:

a(CHEBI:"alpha-tocopherol") decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:"alpha-tocopherol") decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:

a(CHEBI:"alpha-tocopherol") decreases p(HGNC:IL6) View Subject | View Object

Appears in Networks:

Evidence 7e4f4e3848
JSON

Glial activation, pro-inflammatory gene expression and elevated secretion of IL-1, IL-6 and TNF- are consequences of high A levels [30,31].

a(CHEBI:"amyloid-beta") increases bp(GO:"glial cell activation") View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") increases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") increases sec(p(HGNC:IL1B)) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") increases sec(p(HGNC:IL6)) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") increases sec(p(HGNC:TNF)) View Subject | View Object

Appears in Networks:

Evidence 9dc8ae74c6
JSON

Furthermore, A induced NF-B activity in glial and neuronal cells. NF-B is involved in inflammatory responses and is expressed in brains of AD patients [32].

a(CHEBI:"amyloid-beta") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glial cell

bp(GO:"inflammatory response") association act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glial cell

act(p(FPLX:NFkappaB)) association bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
glial cell

p(FPLX:NFkappaB) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 5b25b206bc
JSON

It revealed potent anti-histone acetyltransferase (HAT) activity and inhibited RelA acetylation via direct inhibition of HAT enzymes and consequently down-regulation ofdiverse inflammatory signaling pathways [163].

a(CHEBI:"gallic acid") decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

a(CHEBI:"gallic acid") decreases act(p(FPLX:MYST)) View Subject | View Object

Appears in Networks:

a(CHEBI:"gallic acid") decreases p(HGNC:RELA, pmod(Ac)) View Subject | View Object

Appears in Networks:

Evidence 9b389c4bba
JSON

A-activated NF-B activity and the expression of cytokines were attenuated with gallic acid in microglial cells y decreased acetylation of RelA, which subsequently reduced A-activated neu-rotoxicity [164].

a(CHEBI:"gallic acid") decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"gallic acid") decreases act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 701073c869
JSON

Macranthoin G inhibited the NF-B pathway and activated the phosphorylation of IB, p38 and ERK, and thus, min-imized cell damage [131].

a(CHEBI:"methyl 3,5-di-O-caffeoyl quinate") decreases bp(GO:"NIK/NF-kappaB signaling") View Subject | View Object

Appears in Networks:

a(CHEBI:"methyl 3,5-di-O-caffeoyl quinate") increases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:"methyl 3,5-di-O-caffeoyl quinate") increases p(HGNC:MAPK14, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:"methyl 3,5-di-O-caffeoyl quinate") increases p(FPLX:ERK, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence b6f9a7c2ec
JSON

ROS activate various downstream signaling molecules, such as PKC and mitogen-activated protein kinases (MAPKs) that induce nuclear translocation of NF-B and the expression of pro-inflammatory genes [41].

a(CHEBI:"reactive oxygen species") increases act(p(FPLX:PKC)) View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") increases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) increases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:

Evidence 295a8df1bf
JSON

The phosphorylation of the NF-B inflamma-tory pathway in A 25-35-stimulated microglial cells was inhibited by vitamin D2 via reducing ROS and inflammatory cytokines [207]

a(CHEBI:"vitamin D") decreases p(FPLX:NFkappaB, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"vitamin D") decreases a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"vitamin D") decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 7119a2ac1c
JSON

Anatabine lowered NF-B activation by inhibiting A production in vitro [195].

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

Evidence b53848c57e
JSON

It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195].

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 195cac6b4f
JSON

Geniposide considerably suppressed RAGE-related signaling such as ERK and IB/NF-B, the expression of TNF-, IL-1 and cerebral A accumulation in vivo[245]

a(CHEBI:Geniposide) decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:

a(CHEBI:Geniposide) decreases act(p(FPLX:IKB)) View Subject | View Object

Appears in Networks:

a(CHEBI:Geniposide) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:Geniposide) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(CHEBI:Geniposide) decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:

a(CHEBI:Geniposide) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

Evidence 5e2292d515
JSON

Salidroside ameliorated cognitive injury in an AD rat model by regulating the expressions of thioredoxin, thioredoxin interacting protein and NF-B pathway proteins such as NF-B p65, IB, IKK and IKK[137].

a(CHEBI:Salidroside) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:Salidroside) regulates p(HGNC:TXN) View Subject | View Object

Appears in Networks:

a(CHEBI:Salidroside) regulates p(HGNC:TXNIP) View Subject | View Object

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a(CHEBI:Salidroside) regulates p(HGNC:RELA) View Subject | View Object

Appears in Networks:

a(CHEBI:Salidroside) regulates p(HGNC:NFKBIA) View Subject | View Object

Appears in Networks:

a(CHEBI:Salidroside) regulates p(HGNC:CHUK) View Subject | View Object

Appears in Networks:

a(CHEBI:Salidroside) regulates p(HGNC:IKBKB) View Subject | View Object

Appears in Networks:

Evidence d2c48a609e
JSON

Berberine suppressed inflammatory events occurring in several inflammation-related diseases [186,187].

a(CHEBI:berberine) decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

Evidence 3843e7e479
JSON

Furthermore, berberine decreased the phosphorylation and expression of p65 [188].

a(CHEBI:berberine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:berberine) decreases p(HGNC:RELA) View Subject | View Object

Appears in Networks:

Evidence a0ebc86fe2
JSON

Also, berberine inhibited the phosphorylation of IB.

a(CHEBI:berberine) decreases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 2696be7dae
JSON

Berberine inhibited the p38,ERK and Akt signaling pathways, which were stimulated by A

a(CHEBI:berberine) decreases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:

a(CHEBI:berberine) decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:

a(CHEBI:berberine) decreases act(p(FPLX:AKT)) View Subject | View Object

Appears in Networks:

Evidence 477721f6e5
JSON

Curcumin showed several anti-inflammatory characteristics. It deploys various cytokine-inhibitory, anti-inflammatory activities and decreases the expression levels of COX-2, LOX, and iNOS. Moreover, the expression of the pro-inflammatory cytokines, for instance, TNF-, IL-1, -2,-6, -8, and -12 and the neurotoxic factors were suppressed by curcumin in lipopolysaccharide (LPS)-stimulated monocytes and alveolar macrophages [103].

a(CHEBI:curcumin) decreases bp(GO:"inflammatory response") View Subject | View Object

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a(CHEBI:curcumin) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:LOX) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:IL1A) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:IL2) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:IL6) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:CXCL8) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:IL12B) View Subject | View Object

Appears in Networks:

Evidence 87c75a4107
JSON

Inhibition of the NF-B pathway represents a well-defined anti-inflammatory mechanism of curcumin[104,105]. Curcumin inhibited the phosphorylation and degrada-tion of IB and the nuclear translocation of NF-B p65 [106].

a(CHEBI:curcumin) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases deg(p(HGNC:NFKBIA)) View Subject | View Object

Appears in Networks:

a(CHEBI:curcumin) decreases tloc(p(HGNC:RELA), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

Evidence 0d19fc302f
JSON

It inhibits AChE competitively and reversibly, causing elevated cerebral concen-trations of ACh, and thus, enhancing cholinergic activity.

a(CHEBI:galanthamine) decreases act(p(HGNC:ACHE)) View Subject | View Object

Appears in Networks:

a(CHEBI:galanthamine) increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

Evidence fce78049a7
JSON

Besides, galantamine allosterically interacted with nicotinic ACh receptors to increase the agonistic activity of these receptors and amplified the ACh reaction through stimulating ACh release [165–167].

a(CHEBI:galanthamine) increases sec(a(CHEBI:acetylcholine)) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:galanthamine), p(FPLX:CHRN)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence cac13bf3a4
JSON

The protective effects of galantamine in brain microvascular endothelial cells were mediated via protective gene, heme oxygenase-1 induction through NF-B activation [168]

a(CHEBI:galanthamine) increases act(p(HGNC:HMOX1)) View Subject | View Object

Appears in Networks:

a(CHEBI:galanthamine) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence c379fd27a3
JSON

Pretreatment with genistein significantly alleviated A 25-35-stimulated TLR4 and NF-B expres-sion, DNA binding and NF-B activities[159].

a(CHEBI:genistein) decreases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:

a(CHEBI:genistein) decreases p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:

a(CHEBI:genistein) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:genistein) decreases complex(a(MESH:DNA), p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 0949ec975a
JSON

It improved ICV A 1-42-activated spatial learning, and memory deficiencies were ameliorated via the interference of NF-B signaling and the inhibition of inflammatory cytokines [155].

a(CHEBI:lycopene) increases path(MESH:"Spatial Learning") View Subject | View Object

Appears in Networks:

a(CHEBI:lycopene) increases bp(GO:memory) View Subject | View Object

Appears in Networks:

a(CHEBI:lycopene) decreases bp(GO:"NIK/NF-kappaB signaling") View Subject | View Object

Appears in Networks:

Evidence 98a1554b9b
JSON

It inhibited the activation of NF-B in TNF- induced HepG2 cells [193].

a(CHEBI:oridonin) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence a26a1bff51
JSON

Besides, it attenuated cognitive disorders nd inflam-matory reactions in A 1-42-activated AD mice[194].

a(CHEBI:oridonin) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:oridonin) decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 4875992e05
JSON

It is even more potent than resveratrol through PPAR regulation [118,119], NF-B transcription[120–122] and JNK phosphorylation [123,124].

a(CHEBI:pterostilbene) regulates p(HGNC:PPARA) View Subject | View Object

Appears in Networks:

a(CHEBI:pterostilbene) regulates p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:

a(CHEBI:pterostilbene) regulates p(FPLX:JNK, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 69b996c362
JSON

Resveratrol crossed the blood-brain barrier (BBB) [111,112] and down-regulated several inflammatory biomarkers such as TNF-, COX2 and interleukins [113,114].

a(CHEBI:resveratrol) decreases a(MESH:Interleukins) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

Evidence 7a1127b9b6
JSON

It also lowered the expression of NO and iNOS, and prostaglandin E2 (PGE2) and COX2 in A-activated glial cells. All these effects were attributableto their suppression of nuclear NF-B translocation [116].

a(CHEBI:resveratrol) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases a(CHEBI:"prostaglandin E2") View Subject | View Object

Appears in Networks:

Evidence b27068494a
JSON

Besides, it decreased the phosphorylation of IKK and IB through LPS stimulation and subse-quently inhibited the activity of NF-B [115].

a(CHEBI:resveratrol) decreases p(FPLX:"IKK_complex", pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 6fe921c30b
JSON

Resveratrol disrupted the phosphorylation of signal transducer and activator of transcription factor 1 (STAT1) and STAT3 [115].

a(CHEBI:resveratrol) decreases p(HGNC:STAT1, pmod(Ph)) View Subject | View Object

Appears in Networks:

a(CHEBI:resveratrol) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 452e1c6251
JSON

Xanthoceraside alleviated the A 25-35-stimulated spatial memory deficiencies and oxidative stress in mouse models [246].

a(PUBCHEM:102336202) increases path(MESH:"Spatial Memory") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:102336202) decreases path(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence fca81ab6e3
JSON

It down-regulated iNOS expression and nitrotyrosin levels in the hip-pocampus and stimulated the mRNA expression level of IL-4 [247].

a(PUBCHEM:102336202) decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

a(PUBCHEM:102336202) decreases a(CHEBI:nitrotyrosine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

a(PUBCHEM:102336202) increases r(HGNC:IL4) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

Evidence 9a747fb792
JSON

Furthermore, it inhibited pro-inflammatory cytokines, which were induced by A 25-35/IFN- in microglia cells [248].

a(PUBCHEM:102336202) decreases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 492580ef73
JSON

Xanthoceraside decreased the expression of A 25-35/IFN--stimulated NO, IL-1,and TNF- in microglia, which implicated the down-regulation of the activities of MAPK and NF-B pathways [248]

a(PUBCHEM:102336202) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:102336202) decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:102336202) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:102336202) decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:102336202) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 9895cd3058
JSON

Glaucocalyxin B, found in Rabdosia japonica, considerably atten-uated the expression of NO, TNF-, IL-1, COX-2 and iNOS in LPS-induced microglia cells [169–172]. Moreover, the activation of NF-B, p38 MAPK and ROS generation was interrupted by glauco- calyxin B in LPS-induced microglia cells [172].

a(PUBCHEM:14193399) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases p(HGNC:IL1A) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence 39814c9f15
JSON

Beneficial effects of 4-O-methylhonokinol on memory were observed by the reduction of Aaggregation in A 1-42-injected mice and memory-impaired mice with its anti-oxidative and anti-inflammatory qualities [141–143].

a(PUBCHEM:155160) increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases a(HBP:"amyloid-beta aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases path(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence c87a35db39
JSON

LPS-stimulated memory impairments were improved by 4-O-methylhonokinol through the inhibition of A 1-42 expression.

a(PUBCHEM:155160) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:

Evidence 948d8968f2
JSON

It inactivated– and -secretases and astrocytes through the inter-ference of NF-B activation [144

a(PUBCHEM:155160) decreases act(p(FPLX:"Gamma_secretase")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:155160) decreases act(p(HGNC:BACE1)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:155160) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 7da601e75c
JSON

It inhibited the activation of iNOS, matrix metalloproteinase 2 (MMP2), and NF-Bp65 and consequently prevent AD in the brain [229–231].

a(PUBCHEM:164676) decreases act(p(HGNC:NOS2)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:164676) decreases act(p(HGNC:MMP2)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:164676) decreases act(p(HGNC:RELA)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:164676) decreases path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 30e6d13a48
JSON

Moreover, tanshinone IIA inhibited apoptosis in A 25-35-induced cells [232] and exerted anti-inflammatory activity in atherosclerosis and neuroprotective activity in cerebral ischemia/reperfusion impairment [233,234]

a(PUBCHEM:164676) decreases bp(GO:"apoptotic process") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:164676) decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Atherosclerosis

a(PUBCHEM:164676) decreases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain Ischemia

Evidence 47e4ca9ed0
JSON

Tanshinone IIA reduced the glial fibrillary acidic protein (GFAP) and NF-B and induced the expression of neuronal nuclear antigen (NeuN), Nissl bodies, and IB in AD [235,236].

a(PUBCHEM:164676) decreases p(HGNC:GFAP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:164676) decreases p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:164676) increases p(HGNC:RBFOX3) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:164676) increases a(MESH:"Nissl Bodies") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:164676) increases p(FPLX:IKB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence b6096a36ee
JSON

Ginsenoside Rd showed neuro-protective effects with A 40 activated impairments in rat brains [225] and ameliorated learning and memory capability in APP transgenic mice, via reducing the activity of NF-B [226].

a(PUBCHEM:24721561) decreases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

a(PUBCHEM:24721561) increases bp(GO:learning) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:24721561) increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:24721561) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 9a19c17951
JSON

A levels in the brain of mice were consider-ably reduced with treatment of ginsenoside Re\Rg3\Rg1 (25 mg/kg)[224].

a(PUBCHEM:441923) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

a(PUBCHEM:3086007) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

a(PUBCHEM:441921) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

a(PUBCHEM:9918693) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

Evidence b4324931a1
JSON

LPS-activated expression of pro-inflammatory and neurotoxic factors like NO, TNF-, PGE2, NO synthase and COX2 production and LOX activity were inhibited by dihydroasparagusic acid in microglia cells [243].

a(PUBCHEM:440312) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases a(CHEBI:"prostaglandin E2") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases act(p(HGNC:LOX)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell

Evidence f1db942b71
JSON

Besides, it significantly decreased the generation of ROS and affected LPS-induced activation of MAPK, including p38 and NF-B signaling[243].

a(PUBCHEM:440312) decreases a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:

a(PUBCHEM:440312) decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:440312) decreases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:440312) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence f6db7b1359
JSON

The expression of the protein and mRNA of TLR3, TLR4, NF-B and TNF receptor associated factor 6 (TRAF-6) were substantially decreased by ginsenoside Rg1, and it also decreased the expression of TNF- and IFN- [227]

a(PUBCHEM:441923) decreases r(HGNC:TLR3) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:TLR3) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases r(HGNC:TLR4) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases r(HGNC:TRAF6) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:TRAF6) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:IFNB1) View Subject | View Object

Appears in Networks:

Evidence a5fe7228e6
JSON

Paeoniflorin improved memory impairments and lowered A accumulation in APP/PS1 trans-genic mice [1].

a(PUBCHEM:442534) increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:442534) decreases a(HBP:"amyloid-beta aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence ea453d4d5f
JSON

It attenuated the development of AD by inhibiting glycogen synthase kinase 3 (GSK-3) and NF-B activation, and sup-pressing the NLRP3 inflammasome and cytokines such as TNF-and IL-1 [1].

a(PUBCHEM:442534) decreases path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

a(PUBCHEM:442534) decreases act(p(FPLX:GSK3)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:442534) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:442534) decreases bp(GO:"NLRP3 inflammasome complex assembly") View Subject | View Object

Appears in Networks:

a(PUBCHEM:442534) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(PUBCHEM:442534) decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:

Evidence 0573b93716
JSON

Retinoic acid showed anti-inflammatory qualities via suppressing the expression of the inflammatory mediators IL-6, IL-12 and TNF- [216–219] and mod-ulating NF-B signaling [220,221].

a(PUBCHEM:444795) decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

a(PUBCHEM:444795) decreases p(HGNC:IL6) View Subject | View Object

Appears in Networks:

a(PUBCHEM:444795) decreases p(HGNC:IL12B) View Subject | View Object

Appears in Networks:

a(PUBCHEM:444795) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(PUBCHEM:444795) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 92450612c0
JSON

It reduced BACE1 expression and repressed LPS-activated nuclear translocation of NF-B and its binding to the BACE1 promoter [222].

a(PUBCHEM:444795) decreases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:444795) decreases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

Evidence 8b2099f41f
JSON

Punicalagin decreased the expression of COX2 and DNA binding of NF-B in human colon cancer cell line [126].

a(PUBCHEM:44584733) decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

a(PUBCHEM:44584733) decreases complex(a(MESH:DNA), p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 6945c38994
JSON

Inflammation caused by LPS was reduced with treatment of punicalaginin RAW264.7 macrophages, astrocytes and microglial BV-2 cells

a(PUBCHEM:44584733) decreases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Cell Ontology (CL)
macrophage
Cell Ontology (CL)
microglial cell

Evidence d700fd366b
JSON

ICV infusion of impairments by A 1-42 was considerably reduced with the treatment of obovatol [161].

a(PUBCHEM:45270574) decreases act(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Appears in Networks:

Evidence b7f28ce9c9
JSON

Tetrandrine inhibited the activity of NF-B and down-regulated the expression of pro-inflammatory cytokines [178–180].

a(PUBCHEM:73078) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:

Evidence 6e5e3c5a9e
JSON

It ameliorated spatial learning and memory disorder, which was caused by A 1-42 and was associated with the inter-ference of NF-B activity and the inhibition of IL-1 and TNF-expression [183].

a(PUBCHEM:73078) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) increases path(MESH:"Spatial Learning") View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) increases bp(GO:memory) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

Evidence e0ce441710
JSON

It inhibited the degradation of IkBa, a cytoplasmic NF-B inhibitor, and p65translocation to the nucleus by disabling IkBa alpha kinase beta and  activiies [181,182].

a(PUBCHEM:73078) decreases deg(p(HGNC:NFKBIA)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases tloc(p(HGNC:RELA), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases act(p(HGNC:CHUK)) View Subject | View Object

Appears in Networks:

a(PUBCHEM:73078) decreases act(p(HGNC:IKBKB)) View Subject | View Object

Appears in Networks:

p(HGNC:NFKBIA) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 547ccdb436
JSON

Degeneration of neurons in the brain of AD patients is associated with the activation of NF-B [7

act(p(FPLX:NFkappaB)) association path(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(HP:Neurodegeneration) association act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence e29a5d84e3
JSON

NF-B activation mediates the expression of the pro-oxidant NAPDH oxidase, cyclooxygenase 2 (COX2), interleukins and the antioxidant enzyme, superoxide dismutase (SOD) [78]. Additionally, NF-B activity is associated with the expression of BACE1 [79] and the activation of nucleotide-binding oligomerization domain-like receptor (NALP) 3 inflammosome [80].

act(p(FPLX:NFkappaB)) regulates p(FPLX:"NADPH_oxidase") View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) regulates p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) regulates a(MESH:Interleukins) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) regulates p(FPLX:SOD) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) increases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.