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(7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling

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Abstract

(7R,8S)-Dehydrodiconiferyl alcohol (DDA), a lignan isolated from the dried stems of Clematis armandii, has been found to exert potential anti-inflammatory activity in vitro. In the present study, we investigated the effects and possible mechanisms of DDA on lipopolysaccharide (LPS)-mediated inflammatory response in murine BV2 microglia. Our results revealed that non-toxic concentrations (6.25–25 μM) of DDA markedly suppressed LPS-induced production of nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and release of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration dependent manner. In addition, DDA time- and concentration-dependently attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase 1/2 (JNK), but not protein kinase B, p38, or extracellular signal-regulated kinase 1/2. Moreover, DDA significantly suppress LPS-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Collectively, our results demonstrated that DDA inhibited LPS-stimulated inflammatory response in BV2 cell, at least in part, through inhibition of NF-κB activation and modulation of JNK signaling.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (Nos. 81470164, 81573420 and 81330080) and the National Basic Research Program of China (973 Program, No. 2013CB530700).

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    Authors and Affiliations

    1. Department of Pharmacology, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai, 201203, China

      Si-Yu Liu, Peng Xu, Xiao-Ling Luo & Xin-Hua Liu

    2. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China

      Jin-Feng Hu

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    Correspondence to Jin-Feng Hu or Xin-Hua Liu.

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    Si-Yu Liu and Peng Xu have contributed equally to this work.

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    Liu, SY., Xu, P., Luo, XL. et al. (7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling. Neurochem Res 41, 1570–1577 (2016). https://doi.org/10.1007/s11064-016-1870-8

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