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The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice

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Abstract

The purpose of the present study was to evaluate the protective effect of Palmatine on LPS-induced depressive like behavior and explore its potential mechanism. The mice were intragastrically treated with Fluoxetine or Palmatine once daily for 1 week. After the last drug administration, the mice were intraperitoneally challenged with LPS and suffered for Sucrose preference test, Tail suspension test, Forced swimming test and Open field test. The pro-inflammatory biomarkers were measured by ELISA, qPCR, WB and immunofluorescence. As a result, the administration of Palmatine effectively lessened depressive-like behavior. Palmatine could decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, the expressions of CD68, iNOS mRNA, as well as increase the levels of anti-inflammatory cytokines IL-4, IL-10, the expressions of CD206, Arg1 mRNA, Ym1 mRNA both in LPS-induced mice and in LPS-induced BV2 cells. The beneficial effect of Palmatine might be attributed to the suppression of M1 microglia polarization and the promotion of M2 microglia polarization via PDE4B/KLF4 signaling. The similar results were observed in CUMS-induced depressive mice. The transfection with PDE4B SiRNA or KLF4 SiRNA indicated that PDE4B and KLF4 were both involved in the Palmatine-mediated microglia polarization. Molecular docking indicated that Palmatine could interact with PDE4B. In conclusion, this research demonstrated that Palmatine attenuated depressive like behavior by modulating microglia polarization via PDE4B/KLF4 signaling.

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Acknowledgements

The present study was supported by teaching and research project of Jiangsu Health Vocational College(JKA201815, JKC201939, JKA202003), Natural science fund for colleges and universities in Jiangsu Province(21KJB310011) and enterprise practice training project for young teachers in Higher Vocational Colleges of Jiangsu Province(2020QYSJPX115).

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Authors and Affiliations

  1. School of Pharmacy, Jiangsu Health Vocational College, No.69, Huangshanling Road, 211800, Nanjing, China

    Lei Wang, Aiping Qin & Jinchun Wang

  2. Department of pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, 250014, Jinan, China

    Min Li

  3. Pukou branch of Jiangsu Province Hospital, No.166, Shanghe street, 211800, Nanjing, China

    Cuiping Zhu

  4. Department of Pharmacy, Xiamen Haicang Hospital, No. 89, Haiyu Road, 361026, Xiamen, China

    Xianni Wei

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  1. Lei Wang
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Wang, L., Li, M., Zhu, C. et al. The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice. Neurochem Res 47, 3178–3191 (2022). https://doi.org/10.1007/s11064-022-03672-3

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