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Protective Effect of Silibinin on Learning and Memory Impairment in LPS-Treated Rats via ROS–BDNF–TrkB Pathway

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Abstract

Silibinin, a flavonoid derived from the herb milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1β and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS–BDNF–TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.

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Acknowledgments

This research was supported by National Natural Science Foundation of China (No. 81273517).

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Authors and Affiliations

  1. China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Xiaoyu Song, Biao Zhou, Pingping Zhang, Di Lei, Yubin Wang, Guodong Yao, Toshihiko Hayashi, Mingyu Xia & Takashi Ikejima

  2. Institute for Clinical and Biomedical Sciences, Kyoto, 603-8072, Japan

    Shin-ichi Tashiro

  3. Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan

    Satoshi Onodera

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  1. Xiaoyu Song
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  2. Biao Zhou
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Correspondence to Takashi Ikejima.

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Song, X., Zhou, B., Zhang, P. et al. Protective Effect of Silibinin on Learning and Memory Impairment in LPS-Treated Rats via ROS–BDNF–TrkB Pathway. Neurochem Res 41, 1662–1672 (2016). https://doi.org/10.1007/s11064-016-1881-5

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  • DOI: https://doi.org/10.1007/s11064-016-1881-5

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