Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy

Background: Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.

Methods: In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.

Results: In vitro, API played a crucial role in anti-inflammation and Autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted Autophagy via the phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.

Conclusions: API inhibited degenerative phenotypes and promoted Autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

Apigetrin; MAPK; NF‐κB; PI3K/AKT/mTOR; autophagy; inflammation; intervertebral disk degeneration.