A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Hou, Yue; Zhang, Yuchen; Mi, Yan; Wang, Jian; Zhang, Haotian; Xu, Jikai; Yang, Yanqiu; Liu, Jingyu; Ding, Lingling; Yang, Jingyu; Chen, Guoliang; Wu, Chunfu

doi:10.1002/mnfr.201801380

Cited by 38 publications

(22 citation statements)

References 68 publications

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“…MAPK pathways have been known to be involved in the induction of microglial proinflammatory factor production [48]. In agreement with the previous study [69], our results showed that LPS significantly increased the phosphorylation of ERK, p38, and JNK in the microglial cultures compared with the control cultures. SIS3 significantly induced the phosphorylation of ERK and p38, but not JNK, in the cultures.…”

Section: Discussionsupporting

confidence: 93%

Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson’s disease and roles of microglia, proinflammatory factors, and MAPK

Liu

et al. 2020

J Neuroinflammation

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Background Smad3 signaling is indicated to regulate microglia activity. Parkinson’s disease (PD) neurodegeneration is shown to be associated with aging and neuroinflammation. However, it remains unclear about the relationship among Smad3 signaling, aging, neuroinflammation, and PD. Methods Rats were treated with SIS3 (a specific inhibitor of Smad3, intranigal injection) and/or lipopolysaccharide (intraperitoneal injection). We investigated the effect of SIS3 and lipopolysaccharide and their mechanism of action on motor behavior and nigrostriatal dopaminergic system in the rats. Furthermore, we explored the effect of SIS3 and LPS and their potential signaling mechanism of action on inflammatory response by using primary microglial cultures. Finally, we investigated the relationship among aging, Smad3 signaling, and neuroinflammation using animals of different ages. Results Both SIS3 and lipopolysaccharide induced significant behavior deficits and nigrostriatal dopaminergic neurodegeneration in the rats compared with the vehicle-treated (control) rats. Significantly increased behavior deficits and nigrostriatal dopaminergic neurodegeneration were observed in the rats co-treated with SIS3 and lipopolysaccharide compared with the rats treated with vehicle, SIS3, or lipopolysaccharide. Furthermore, both SIS3 and lipopolysaccharide induced significant microglia activation and proinflammatory factor (IL-1β, IL-6, iNOS, and ROS) level increase in the SN of rats compared with the control rats. Significantly enhanced microglial inflammatory response was observed in the rats co-treated with SIS3 and lipopolysaccharide compared with the other three groups. For our in vitro study, both SIS3 and lipopolysaccharide induced significant proinflammatory factor level increase in primary microglia cultures compared with the control cultures. Significantly increased inflammatory response was observed in the cultures co-treated with SIS3 and lipopolysaccharide compared with the other three groups. MAPK (ERK/p38) contributed to microglial inflammatory response induced by co-treatment with SIS3 and lipopolysaccharide. Interestingly, there was decrease in Smad3 and pSmad3 expression (protein) and enhancement of neuroinflammation in the mouse SN with aging. Proinflammatory factor levels were significantly inversely correlated with Smad3 and pSmad3 expression. Conclusion Our study strongly indicates the involvement of SN Smad3 signaling deficiency in aging and PD neurodegeneration and provides a novel molecular mechanism underlying the participation of aging in PD and helps to elucidate the mechanisms for the combined effect of multiple factors in PD.

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Section: Discussionsupporting

confidence: 93%

Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson’s disease and roles of microglia, proinflammatory factors, and MAPK

Liu

et al. 2020

J Neuroinflammation

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“…Additionally, it has been reported that resveratrol preconditioning modulates inflammatory response of hippocampus after global cerebral ischemia in rat [29]. In addition, resveratrol has been documented to be able to suppress neuro-inflammation mediated by microglia, protect neurons from inflammatory damage, and relieve inflammation of the airway caused by asthma and airway remodeling [30,31].…”

Section: The Anti-inflammatory Activity Of Resveratrolmentioning

confidence: 99%

Anti-Inflammatory Action and Mechanisms of Resveratrol

et al. 2021

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Resveratrol (3,4′,5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms or tissue injury. In this review, the anti-inflammatory activity and the mechanism of resveratrol modulates the inflammatory response are examined. Multiple experimental studies that illustrate regulatory mechanisms and the immunomodulatory function of resveratrol both in vivo and in vitro. The data acquired from those studies are discussed.

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“…10 μM was used as the highest concentration of kellerin in our in vitro study according to our previous study (Xing et al, ). Cell viability was examined using the MTT assay as previously reported (Hou et al, ).…”

Section: Methodsmentioning

confidence: 99%

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Zhang

Jiang

et al. 2020

Phytotherapy Research

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Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.

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A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Cited by 38 publications

References 68 publications

Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson’s disease and roles of microglia, proinflammatory factors, and MAPK

Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson’s disease and roles of microglia, proinflammatory factors, and MAPK

Anti-Inflammatory Action and Mechanisms of Resveratrol

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

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