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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1434652

Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes

Provisionally accepted
Feng Sa Feng Sa 1Linyan Liu Linyan Liu 1Yuelin Cheng Yuelin Cheng 1Zhou Mengmeng Zhou Mengmeng 1Haoqiang Zhu Haoqiang Zhu 1Xinyan Zhao Xinyan Zhao 1Ziyu Chen Ziyu Chen 1Shunli Kan Shunli Kan 1Xuanhao Fu Xuanhao Fu 1Wei Hu Wei Hu 1Rusen Zhu Rusen Zhu 2*
  • 1 Tianjin Union Medical Centre, Nankai University, Tianjin, China
  • 2 Tianjin People's Hospital, Tianjin, China

The final, formatted version of the article will be published soon.

    The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) inhibits reactive astrocytes in spinal cord injury treatment. The research demonstrates that ICA can inhibit reactive astrocyte proliferation in rat post-injury by targeting YAP (Yes-Associated Protein). Furthermore, ICA enhanced functional recovery in female Wistar rats with spinal cord contusion, as evidenced by CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) scores, and electrophysiological measurements. Knocking down PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes inhibits TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through IP-WB (immunoprecipitation-Western Blot) ubiquitination and cytoplasm-nuclear separation. These findings contribute to our understanding of how ICA aids in spinal cord injury repair and offer insights for potential clinical applications.

    Keywords: spinal cord injury, Icariin, reactive astrogliosis, YAP, PPM1B

    Received: 18 May 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Sa, Liu, Cheng, Mengmeng, Zhu, Zhao, Chen, Kan, Fu, Hu and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rusen Zhu, Tianjin People's Hospital, Tianjin, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.