Moreover,it reveals promising anti-inflammatory actions through suppress-ing the activation of NF-B [238–240].
The expression of A was lowered by artemisinin through inhibition of the activity of NALP3 inflammasome in APPswe/PS1E9 transgenic mice [241].
The mitochondrial membrane potential, ROS and NO levels were down-regulated by 1,8-cineole in A 25-35-stimulated cells [250].
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].
Further-more, the expression of NOS-2, COX2 and NF-B was reduced by1,8-cineole [250].
It considerably decreased A 1-42-stimulated memory disorders in mice [128].
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].
Besides, extracellular signal-regulated kinase (ERK), p38 MAPK and NF-B pathway were disrupted byL-theanine [128].
It has antiox-idant effects via the interference of reactive components and ROS by redox cycling of quinine, and subsequently generating hydroquinone [209].
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].
Oxidative stress and A expression were suppressed with -tocopherol in mouse model.
Memory defi-ciencies were improved by -tocopherol in transgenic mice.
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]
Glial activation, pro-inflammatory gene expression and elevated secretion of IL-1, IL-6 and TNF- are consequences of high A levels [30,31].
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].
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-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].
Macranthoin G inhibited the NF-B pathway and activated the phosphorylation of IB, p38 and ERK, and thus, min-imized cell damage [131].
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].
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]
Anatabine lowered NF-B activation by inhibiting A production in vitro [195].
It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195].
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]
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].
Berberine suppressed inflammatory events occurring in several inflammation-related diseases [186,187].
Furthermore, berberine decreased the phosphorylation and expression of p65 [188].
Also, berberine inhibited the phosphorylation of IB.
Berberine inhibited the p38,ERK and Akt signaling pathways, which were stimulated by A
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].
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].
It inhibits AChE competitively and reversibly, causing elevated cerebral concen-trations of ACh, and thus, enhancing cholinergic activity.
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].
The protective effects of galantamine in brain microvascular endothelial cells were mediated via protective gene, heme oxygenase-1 induction through NF-B activation [168]
Pretreatment with genistein significantly alleviated A 25-35-stimulated TLR4 and NF-B expres-sion, DNA binding and NF-B activities[159].
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].
It inhibited the activation of NF-B in TNF- induced HepG2 cells [193].
Besides, it attenuated cognitive disorders nd inflam-matory reactions in A 1-42-activated AD mice[194].
It is even more potent than resveratrol through PPAR regulation [118,119], NF-B transcription[120–122] and JNK phosphorylation [123,124].
Resveratrol crossed the blood-brain barrier (BBB) [111,112] and down-regulated several inflammatory biomarkers such as TNF-, COX2 and interleukins [113,114].
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].
Besides, it decreased the phosphorylation of IKK and IB through LPS stimulation and subse-quently inhibited the activity of NF-B [115].
Resveratrol disrupted the phosphorylation of signal transducer and activator of transcription factor 1 (STAT1) and STAT3 [115].
Xanthoceraside alleviated the A 25-35-stimulated spatial memory deficiencies and oxidative stress in mouse models [246].
It down-regulated iNOS expression and nitrotyrosin levels in the hip-pocampus and stimulated the mRNA expression level of IL-4 [247].
Furthermore, it inhibited pro-inflammatory cytokines, which were induced by A 25-35/IFN- in microglia cells [248].
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]
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].
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].
LPS-stimulated memory impairments were improved by 4-O-methylhonokinol through the inhibition of A 1-42 expression.
It inactivated– and -secretases and astrocytes through the inter-ference of NF-B activation [144
It inhibited the activation of iNOS, matrix metalloproteinase 2 (MMP2), and NF-Bp65 and consequently prevent AD in the brain [229–231].
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]
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].
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 levels in the brain of mice were consider-ably reduced with treatment of ginsenoside Re\Rg3\Rg1 (25 mg/kg)[224].
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].
Besides, it significantly decreased the generation of ROS and affected LPS-induced activation of MAPK, including p38 and NF-B signaling[243].
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]
Paeoniflorin improved memory impairments and lowered A accumulation in APP/PS1 trans-genic mice [1].
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].
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].
It reduced BACE1 expression and repressed LPS-activated nuclear translocation of NF-B and its binding to the BACE1 promoter [222].
Punicalagin decreased the expression of COX2 and DNA binding of NF-B in human colon cancer cell line [126].
Inflammation caused by LPS was reduced with treatment of punicalaginin RAW264.7 macrophages, astrocytes and microglial BV-2 cells
ICV infusion of impairments by A 1-42 was considerably reduced with the treatment of obovatol [161].
Tetrandrine inhibited the activity of NF-B and down-regulated the expression of pro-inflammatory cytokines [178–180].
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].
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].
Degeneration of neurons in the brain of AD patients is associated with the activation of NF-B [7
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].
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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.