Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects.
J Orthop Translat
; 39: 74-87, 2023 Mar.
Article
en En
| MEDLINE
| ID: mdl-36788965
ABSTRACT
Background:
The incidence of intervertebral disc degeneration (IVDD) is a common degenerative disease with inflammation, decreased autophagy, and progression of fibrosis as its possible pathogenesis. Physalin A (PA) is a widely studied anti-inflammatory drug. However, its therapeutic effects on IVDD remain unexplored. Therefore, we aimed to explore the therapeutic potential of PA in IVDD progression. Materials andmethods:
In vivo, we investigated PA bioactivity using a puncture-induced IVDD rat model. IVDD signals and height changes were detected using X-ray, micro-CT, and MRI, and structural and molecular lesions using histological staining and immunohistochemistry of intervertebral disc sections. In vivo, interleukin-1 beta (IL-1ß) and TGF-ß1 were employed to establish inflammation fibrotic nucleus pulposus (NP) cells. The PA effect duration, concentration, influence pathways, and pathological changes in IVDD treatment were elucidated using western blotting, real-time PCR, and immunofluorescence.Results:
PA exerted significant effects on IVDD remission due to anti-inflammation, fibrosis reduction, and autophagy enhancement. In vitro, PA improved inflammation by blocking the NF-κB and MAPK pathways, whereas it promoted autophagy via the PI3K/AKT/mTOR pathway and affected fibrotic progression by regulating the SMAD2/3 pathway. Moreover, PA improved the disc degeneration process in IVDD model.Conclusions:
PA exhibited significant anti-inflammatory and anti-fibrotic effects and improved autophagy in vivo and in vitro IVDD models, thus effectively relieving IVDD progression, indicating it is a promising agent for IVDD treatment. The translational potential of this article This study successfully reveals that PA, a natural bioactive withanolide, effectively relieved IVDD progression via inflammation inhibition, fibrosis reduction, and autophagy enhancement, indicating it is a promising agent for IVDD treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Orthop Translat
Año:
2023
Tipo del documento:
Article
País de afiliación:
China