Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA21mediated PTEN/AKT/mTOR pathway.
Int J Mol Med
; 48(2)2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34132355
ABSTRACT
Gypenoside XVII (GP17), 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 GP17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP17 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 GP17 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 GP17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP17. The inhibition of miR21 eliminated the protective effects of GP17 on SCIinduced 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 miR21, and PTEN expression was downregulated by GP17 through miR21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was reactivated by GP17 through the regulation of miR21 in mice with SCI. On the whole, the findings of the present study suggest that GP17 plays a protective role in SCI via regulating the miR21/PTEN/AKT/mTOR pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saponins
/
Spinal Cord Injuries
/
MicroRNAs
/
PTEN Phosphohydrolase
/
Proto-Oncogene Proteins c-akt
/
TOR Serine-Threonine Kinases
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2021
Document type:
Article