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

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

Evidence ad2e280756

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

Evidence ed9564e074

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

Evidence e29b75b023

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].

Evidence e8cbf8f866

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

Evidence fd54e77d1e

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

Evidence f465e0e23e

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].

Evidence d37faf5f17

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

Evidence 5b31fa7f01

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

Evidence 86a01eb22a

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].

Evidence 4036caa9dc

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

Evidence 6df3bc0175

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

Evidence bebd9c97ef

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]

Evidence 7e4f4e3848

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

Evidence 9dc8ae74c6

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].

Evidence 5b25b206bc

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].

Evidence 9b389c4bba

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].

Evidence 701073c869

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

Evidence b6f9a7c2ec

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].

Evidence 295a8df1bf

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]

Evidence 7119a2ac1c

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

Evidence b53848c57e

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

Evidence 195cac6b4f

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]

Evidence 5e2292d515

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].

Evidence d2c48a609e

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

Evidence 3843e7e479

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

Evidence a0ebc86fe2

Also, berberine inhibited the phosphorylation of IB.

Evidence 2696be7dae

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

Evidence 477721f6e5

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].

Evidence 87c75a4107

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].

Evidence 0d19fc302f

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

Evidence fce78049a7

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].

Evidence cac13bf3a4

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

Evidence c379fd27a3

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

Evidence 0949ec975a

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].

Evidence 98a1554b9b

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

Evidence a26a1bff51

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

Evidence 4875992e05

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

Evidence 69b996c362

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

Evidence 7a1127b9b6

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].

Evidence b27068494a

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

Evidence 6fe921c30b

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

Evidence 452e1c6251

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

Evidence fca81ab6e3

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

Evidence 9a747fb792

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

Evidence 492580ef73

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]

Evidence 9895cd3058

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].

Evidence 39814c9f15

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].

Evidence c87a35db39

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

Evidence 948d8968f2

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

Evidence 7da601e75c

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

Evidence 30e6d13a48

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]

Evidence 47e4ca9ed0

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].

Evidence b6096a36ee

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].

Evidence 9a19c17951

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

Evidence b4324931a1

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].

Evidence f1db942b71

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

Evidence f6db7b1359

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]

Evidence a5fe7228e6

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

Evidence ea453d4d5f

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].

Evidence 0573b93716

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].

Evidence 92450612c0

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

Evidence 8b2099f41f

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

Evidence 6945c38994

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

Evidence d700fd366b

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

Evidence b7f28ce9c9

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

Evidence 6e5e3c5a9e

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].

Evidence e0ce441710

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].

Evidence 547ccdb436

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

Evidence e29a5d84e3

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.