4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase

Lee, Yong Kyung; Choi, Im Seop; Ban, Jung Ok; Lee, Hwa Jeong; Lee, Ung Soo; Han, Sang Bae; Jung, Jae Kyung; Kim, Young Hee; Kim, Ki Ho; Oh, Ki‐Wan; Hong, Jin Tae

doi:10.1016/j.jnutbio.2010.04.002

Cited by 40 publications

(26 citation statements)

References 66 publications

(84 reference statements)

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“…LPS-treated mice exhibited increases in both the levels of inflammatory products and amyloid formation as well as in secretases activity in the neurons of the mouse brain [64]. We also found that 4- O -methylhonokiol prevented the activation of astrocytes in culture or in the brain of AD-model mice such as Aβ-injected or PS2 mutant transgenic mice [43,44,48]. Moreover, several anti-inflammatory agents have been reported to have anti-amyloidogenic effects.…”

Section: Discussionmentioning

confidence: 94%

“…Dosage (0.5 and 1 mg/kg/day) of 4- O -methylhonokiol in this study was used by referring to our previous studies [43-45,48]. 4- O -methylhonokiol (15 and 30 μg/mouse) was added to drinking water (5 ml of average water consumption of mouse per day) and mice were allowed access for 3 weeks ad libitum before induction of memory impairment as shown in Figure 1B.…”

Section: Methodsmentioning

confidence: 99%

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Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

Lee

Choi

et al. 2012

J Neuroinflammation

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BackgroundNeuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms.MethodsWe investigated whether 4-O-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-O-methylhonkiol (0.5, 1 and 2 μM).ResultsOral administration of 4-O-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-O-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4-O-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-O-methylhonokiol inhibited LPS-induced Aβ1-42 generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.ConclusionThese results suggest that 4-O-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-O-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.

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Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

Lee

Choi

et al. 2012

J Neuroinflammation

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128

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“…Total glutathione levels in brain tissue were determined using a glutathione assay kit (Cayman Chemical) according to the manufacturer's instructions as described elsewhere [22]. Carbonyl protein content and glutathione levels were expressed as nanomole per milligram of protein.…”

Section: Determination Of Carbonyl Protein and Glutathione Levelsmentioning

confidence: 99%

Thiacremonone Potentiates Anti-Oxidant Effects to Improve Memory Dysfunction in an APP/PS1 Transgenic Mice Model

et al. 2015

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Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) peptide. Evidence suggests that amyloid accumulation can be caused by oxidative stress and inflammatory responses. In this study, we examined neuroprotective effects of thiacremonone, an anti-oxidant and anti-inflammatory compound isolated from garlic. Treatment of thiacremonone significantly attenuated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) double-mutant transgenic mice. In addition, activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) pathways in the brain was potently inhibited by thiacremonone. We also observed that thiacremonone significantly inhibited activation of NF-κB and ERK pathways induced by H2O2 and Aβ1-42 in embryonic neuronal cells. Furthermore, thiacremonone augmented peroxiredoxin 6 (PRDX6) expression in vivo and in vitro associated with reduced oxidative stress of macromolecules such as protein and lipids. This study indicates that thiacremonone might exert memory improvement via stimulating anti-oxidant system. These multiple properties could attenuate Aβ accumulation and oxidative stress in Alzheimer's brains. Thus, these results suggest that thiacremonone might be useful to intervene development or progression of neurodegeneration in AD.

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“…infused mice (Lee et al 2011b), and mice with memory impairment induced by injection of lipopolysaccharide (LPS) (Lee et al 2012b) or scopolamine (Lee et al 2009). Overall, the MH-treated mice show low levels of b-secretase, inducible nitric oxide synthase (iNOS), COX, interleukin (IL)-1b and tumor necrosis factor (TNF)-a, high levels of Ab-degrading peptidases neprilysin, and low numbers of activated astrocytes and microglial cells in the brain.…”

Section: Introductionmentioning

confidence: 99%

Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models

et al. 2014

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4-O-methylhonokiol (MH) is known to inhibit inflammation by partially understood mechanisms. Here, the anti-inflammatory mechanisms of MH were examined using enzymatic, cellular, and animal assays. In enzymatic assays, MH inhibited COX-2 activity with an IC50 of 0.062 μM, and also COX-1 with an IC50 of 2.4 μM. In cellular assays, MH was immunotoxic above 10 μM. At non-toxic concentrations (below 3 μM), MH strongly inhibited COX-2-mediated prostaglandin production with an IC50 of 0.1 μM, whereas did not or slightly affect other functions of B cells, T cells, dendritic cells, and macrophages. In an animal model, MH inhibited the increase in footpad thickness and popliteal lymph node weight in zymosan-injected mice. When analyzed the draining pLNs of zymosan-injected mice on day 5, MH inhibited the overall inflammatory responses. However, MH inhibited cyclooxygenase (COX)-2-mediated prostaglandin production without affecting tumor necrosis factor-α production in inflamed tissues within 6 h after zymosan injection. In summary, our data suggest that COX-2 may be a direct anti-inflammatory target of MH in vitro and in vivo.

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4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase

Cited by 40 publications

References 66 publications

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

Thiacremonone Potentiates Anti-Oxidant Effects to Improve Memory Dysfunction in an APP/PS1 Transgenic Mice Model

Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models

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