Icariin Mediates Reactive Astrocytes after Spinal Cord Injury via YAP and TGF-beta Signaling.

Abstract

Icariin (ICA) is the main active component of the traditional Chinese medicine Epimedium, which has been confirmed to play a neuroprotective role in spinal cord injury (SCI) models. Astrocyte activation is a key link in “inflammatory storms” after SCI, and eventually form glial scar to inhibit neurological recovery. Studies have shown that icariin can effectively inhibit inflammatory response and promote the recovery of nerve function after SCI, but the specific mechanism is still unclear. This study applied network pharmacology and in vivo experimental verification to explore the molecular mechanism of ICA in the treatment of SCI. A total of 37 targets were screened out, mainly enriched in response to hypoxia, response to abiotic stimulus, regulation of cellular response to stress, and the TGF-beta signaling pathway etc. In the animal experiments, the Basso, Beattie and Bresnahan scores and Hematoxylin Eosin staining revealed that ICA could effectively improve the behavioral and histological recovery of SCI rats. Then ICA was confirmed to reduce astrocyte GFAP, Vimentin, and the expression of Ki-67 after SCI. Furthermore, ICA could inhibit the TGF-beta signaling pathway. ICA could also inhibit the expression of Yap protein. However, when Yap protein was activated, ICA inhibited the TGF-beta signaling pathway and reactive astrocyte activation was reversed. To sum up, the mechanism of ICA treatment for SCI may involve the inhibition of reactive astrocyte activation by inhibiting the expression of Yap protein and down-regulating the TGF-beta signaling pathway.