Effects of resveratrol and its derivatives on lipopolysaccharide-induced microglial activation and their structure–activity relationships

Meng, Xianmin; Yang, Jingyu; Chen, Guoliang; Wei, Lihui; Zhang, Lijia; Shu, Wang; Li, Jie; Wu, Chunfu

doi:10.1016/j.cbi.2008.04.015

Cited by 78 publications

(46 citation statements)

References 34 publications

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“…These findings agree with the previous studies in which resveratrol inhibited LPS-induced production of these three proinflammatory factors in primary microglia or microglial cell lines (Bi et al, 2005;CandelarioJalil et al, 2007;Meng et al, 2008). Of the numerous neurotoxic factors released by activated microglia, the consequences of production of NO, TNF␣, and ROS have been relatively well studied (McGuire et al, 2001).…”

Section: Downloaded Fromsupporting

confidence: 92%

Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

Zhang

Shi²,

Zhou³

et al. 2010

Mol Pharmacol

161

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Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra. Accumulating evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for PD. Resveratrol, a nonflavonoid polyphenol naturally found in red wine and grapes, has been known to possess antioxidant, anticancer, and anti-inflammatory properties. Although recent studies have shown that resveratrol provided neuroprotective effects against ischemia, seizure, and neurodegenerative disorders, the mechanisms underlying its beneficial effects on dopaminergic neurodegeneration are poorly defined. In this study, rat primary midbrain neuron-glia cultures were used to elucidate the molecular mechanisms underlying resveratrolmediated neuroprotection. The results clearly demonstrated that resveratrol protected DA neurons against lipopolysaccharide (LPS)-induced neurotoxicity in concentration-and timedependent manners through the inhibition of microglial activation and the subsequent reduction of proinflammatory factor release. Mechanistically, resveratrol-mediated neuroprotection was attributed to the inhibition of NADPH oxidase. This conclusion is supported by the following observations. First, resveratrol reduced NADPH oxidase-mediated generation of reactive oxygen species. Second, LPS-induced translocation of NADPH oxidase cytosolic subunit p47 to the cell membrane was significantly attenuated by resveratrol. Third and most importantly, resveratrol failed to exhibit neuroprotection in cultures from NADPH oxidase-deficient mice. Furthermore, this neuroprotection was also related to an attenuation of the activation of mitogen-activated protein kinases and nuclear factor-B signaling pathways in microglia. These findings suggest that resveratrol exerts neuroprotection against LPS-induced dopaminergic neurodegeneration, and NADPH oxidase may be a major player in resveratrol-mediated neuroprotection.

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Section: Downloaded Fromsupporting

confidence: 92%

Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

Zhang

Shi²,

Zhou³

et al. 2010

Mol Pharmacol

161

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“…Resveratrol has been found to modulate neuroinflammation in both in vivo and in vitro models, specifically targeting activated micloglial cells [71]. Actually, resveratrol suppresses the activation of the NF-kB pathway in LPS-activated microglia by reducing the phosphorylation and consequent degradation of its inhibitor, IkB [72][73][74][75]. Our results demonstrate that microglial, but not astroglial reactivity, was significantly diminished with resveratrol administration compared to untreated SOD1 G93A mice.…”

Section: Discussionmentioning

confidence: 60%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

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Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1 G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests.We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1 G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1 G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

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“…The phosphorylation of MAPKs (ERK1/2, p38 MAPK, and JNK1/2), which are signaling molecules involved in upstream regulation of several transcription factors, has been observed to increase in LPS-stimulated VSMCs [43] . Meng et al reported that the activation of NF-κB was also partially dependent on the phosphorylation of MAPKs [44] . NF-κB upregulates the expression of various proinflammatory cytokines and enzymes by binding with DNA and controlling the transcription of target genes, but only when NF-κB is activated and translocated into the nucleus.…”

Section: Wwwchinapharcom Meng Z Et Almentioning

confidence: 99%

Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways

et al. 2013

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Aim: To investigate whether curcumin (Cur) suppressed lipopolysaccharide (LPS)-induced inflammation in vascular smooth muscle cells (VSMCs) of rats, and to determine its molecular mechanisms. Methods: Primary rat VSMCs were treated with LPS (1 μg/L) and Cur (5, 10, or 30 μmol/L) for 24 h. The levels of MCP-1, TNF-α, and iNOS were measured using ELISA and real-time RT-PCR. NO level was analyzed with the Griess reaction. Western-blotting was used to detect the activation of TLR4, MAPKs, IκBα, NF-κB p65, and the p47 phox subunit of NADPH oxidase in the cells. Results: Treatment of VSMCs with LPS dramatically increased expression of inflammatory cytokines MCP-1 and TNF-α, expression of TLR4 and iNOS, and NO production. LPS also significantly increased phosphorylation of IκBα, nuclear translocation of NF-κB (p65) and phosphorylation of MAPKs in VSMCs. Furthermore, LPS significantly increased production of intracellular ROS, and decreased expression of p47 phox subunit of NADPH oxidase. Pretreatment with Cur concentration-dependently attenuated all the aberrant changes in LPS-treated VSMCs. The LPS-induced overexpression of MCP-1 and TNF-α, and NO production were attenuated by pretreatment with the ERK inhibitor PD98059, the p38 MAPK inhibitor SB203580, the NF-κB inhibitor PDTC or anti-TLR4 antibody, but not with the JNK inhibitor SP600125. Conclusion: Cur suppresses LPS-induced overexpression of inflammatory mediators in VSMCs in vitro via inhibiting the TLR4-MAPK/ NF-κB pathways, partly due to block of NADPH-mediated intracellular ROS production.

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Effects of resveratrol and its derivatives on lipopolysaccharide-induced microglial activation and their structure–activity relationships

Cited by 78 publications

References 34 publications

Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways

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