Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-κB, JNK and p38 MAPK inactivation

Zhou, Hong; Shin, Eun Myoung; Guo, Lian; Youn, Ui Joung; Bae, KiHwan; Kang, Sam Sik; Zou, Li; Kim, Yeong Shik

doi:10.1016/j.ejphar.2008.02.044

Cited by 126 publications

(48 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The information of 4- O -methylhonokiol was previously reported [40,45]. The result was in agreement with previously published data [46,47], and this compound may possibly be the same compound demonstrated by Zhou et al [35]. …”

Section: Methodssupporting

confidence: 92%

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

128

View full text Add to dashboard Cite

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.

show abstract

Section: Methodssupporting

confidence: 92%

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

128

View full text Add to dashboard Cite

show abstract

“…Magnolia extract and its active component MG were found to prevent skin photoaging via inhibition of NF- κ B in mice [36]. Intraperitoneal treatment of MH significantly inhibited acetic acid-induced acute inflammation and carrageenan-induced paw swelling and tissue plasminogen activator induced increase in ear thickness and ear weight [37]. In the study, histological staining showed that mast cells in adipose tissue were obviously reduced in HFD-induced obesity with MH or BL153 treatment (Figure 3(d)).…”

Section: Discussionmentioning

confidence: 99%

TheMagnoliaBioactive Constituent 4-O-Methylhonokiol Protects against High-Fat Diet-Induced Obesity and Systemic Insulin Resistance in Mice

Zhang

Chen

Jiang

et al. 2014

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Obesity is caused by a combination of both genetic and environmental risks. Disruption in energy balance is one of these risk factors. In the present study, the preventive effect on high-fat diet- (HFD-) induced obesity and insulin resistance in mice by Magnolia bioactive constituent 4-O-methylhonokiol (MH) was compared with Magnolia officinalis extract BL153. C57BL/6J mice were fed by normal diet or by HFD with gavage-administered vehicle, BL153, low-dose MH, and high-dose MH simultaneously for 24 weeks, respectively. Either MH or BL153 slightly inhibited body-weight gain of mice by HFD feeding although the food intake had no obvious difference. Body fat mass and the epididymal white adipose tissue weight were also mildly decreased by MH or BL153. Moreover, MH significantly lowered HFD-induced plasma triglyceride, cholesterol levels and activity of alanine transaminase (ALT), liver weight and hepatic triglyceride level, and ameliorated hepatic steatosis. BL153 only significantly reduced ALT and liver triglyceride level. Concurrently, low-dose MH improved HFD-induced hyperinsulinemia and insulin resistance. Furthermore, the infiltration of mast cells in adipose tissue was decreased in MH or in BL153 treatment. These results suggested that Magnolia bioactive constituent MH might exhibit potential benefits for HFD-induced obesity by improvement of lipid metabolism and insulin resistance.

show abstract

“…To mention a few examples, torilin, obtained from Ulmus davidiana japonica, inhibited LPS-induced iNOS, COX-2 and IL-1β in the microglial cell line BV2, via down-regulation of ERK1/2, p38 MAPK, NF-κB and CREB [88]; 4-methoxyhonokiol, an active anti-inflammatory constituent of the bark of Magnolia obovata , significantly inhibited LPS-induced expression of iNOS and COX-2 in RAW 264.7 macrophages, acting on JNK and p38 MAPK signal pathways and NF-κB activation [89]. Finally, studies performed in primary microglial cultures showed that macelignan, a compound extracted from Myristica fragrans , inhibits iNOS expression at the transcriptional level [90] and the production of TNF-α and IL-6.…”

Section: Natural Anti-inflammatory Drugsmentioning

confidence: 99%

Non-Steroidal Anti-Inflammatory Drugs and Brain Inflammation: Effects on Microglial Functions

Ajmone‐Cat¹,

Bernardo²,

Greco³

et al. 2010

Pharmaceuticals

104

View full text Add to dashboard Cite

The term NSAID refers to structurally diverse chemical compounds that share the ability to inhibit the activity of the prostaglandin (PG) biosynthetic enzymes, the cyclooxygenase (COX) isoforms 1 and 2. The suppression of PG synthesis at sites of inflammation has been regarded as primarily responsible for the beneficial properties of NSAIDs, but several COX-independent effects have been described in recent years. Epidemiological studies indicate that NSAIDs are neuroprotective, although the mechanisms underlying their beneficial effect remain largely unknown. Microglial cells play a major role in brain inflammation and are often viewed as major contributors to the neurodegeneration. Therefore, microglia represent a likely target for NSAIDs within the brain. In the present review, we focused on the direct effects of NSAIDs and selective COX-2 inhibitors on microglial functions and discuss the potential efficacy in controlling brain inflammation.

show abstract

Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-κB, JNK and p38 MAPK inactivation

Cited by 126 publications

References 37 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

TheMagnoliaBioactive Constituent 4-O-Methylhonokiol Protects against High-Fat Diet-Induced Obesity and Systemic Insulin Resistance in Mice

Non-Steroidal Anti-Inflammatory Drugs and Brain Inflammation: Effects on Microglial Functions

Contact Info

Product

Resources

About