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Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14 Expression and NF-κB and NLRP3 Inflammasome Activation

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Abstract

The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL-6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo. Consistent with these results, the expression levels of TLR4 and CD14 and the phosphorylation of JNK were also reduced. Further study showed that rosmarinic acid suppresses the activation of the NF-κB pathway and NLRP3 inflammasome, which may contribute to its anti-inflammatory effects. These results suggest that rosmarinic acid significantly reduced TLR4 and CD14 expression and NF-κB and NLRP3 inflammasome activation, which is involved in anti-neuroinflammation.

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Acknowledgements

This work was financially supported through grants from the Department of Technology and Science of Fujian Provincial Government (Grant No. 2016Y0055) and the Collaborative Innovation Center for the Rehabilitation Technology of Fujian University of TCM.

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  1. Yicong Wei and Jianxiong Chen contributed equally to this work.

Authors and Affiliations

  1. Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China

    Yicong Wei, Jianxiong Chen, Yonghong Hu, Wei Lu, Xiaoqin Zhang, Ruiguo Wang & Kedan Chu

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  1. Yicong Wei
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Correspondence to Yicong Wei.

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Electronic Supplementary Material

Fig. S1

Rosmarinic acid (RA) does not affect cell viability of BV2 cells. The cytotoxic effect of RA on cultured BV2 cell exposure to LPS. BV2 cells were treated with RA at concentrations of 50, 100, and 200 μM for 24 h in the presence and absence of LPS (100 ng/mL). The cell viability was expressed as the percentage of surviving cells compared with control cells using CKK8 assay. The data are presented as the means ± SEM of three independent experiments (n = 3). (JPEG 220 kb)

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Wei, Y., Chen, J., Hu, Y. et al. Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14 Expression and NF-κB and NLRP3 Inflammasome Activation. Inflammation 41, 732–740 (2018). https://doi.org/10.1007/s10753-017-0728-9

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  • DOI: https://doi.org/10.1007/s10753-017-0728-9

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