Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA‑21‑mediated PTEN/AKT/mTOR pathway.

Abstract

Gypenoside XVII (GP-17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP-17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP-17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP-17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP-17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR-21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP-17. The inhibition of miR-21 eliminated the protective effects of GP-17 on SCI-induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR-21, and PTEN expression was downregulated by GP-17 through miR-21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re-activated by GP-17 through the regulation of miR-21 in mice with SCI. On the whole, the findings of the present study suggest that GP-17 plays a protective role in SCI via regulating the miR-21/PTEN/AKT/mTOR pathway.