Higenamine mitigates interleukin-1β-induced human nucleus pulposus cell apoptosis by ROS-mediated PI3K/Akt signaling

Intervertebral disc degeneration (IDD) is a natural problem linked to the inflammation. Higenamine exerts multiple pharmacological properties in inflammation-related disorders. Our study aimed to explore the function of higenamine on interleukin (IL)-1 beta-caused apoptosis of human nucleus pulposus cells (HNPCs). Cell apoptosis was investigated by TUNEL and flow cytometry. Apoptosis-related biomarkers were determined by qRT-PCR or Western blotting. The protein in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling was measured by Western blotting. We found that higenamine showed little effect on cell apoptosis, but mitigated IL-1 beta-caused apoptosis in a dose-dependent pattern. Higenamine attenuated IL-1 beta-induced decrease of Bcl-2 and increase of Bax and cleaved caspase-3. Higenamine did not affect the reactive oxygen species (ROS) level and the PI3K/Akt signaling, but attenuated IL-1 beta-induced ROS production and inhibition of the PI3K/Akt signaling. IL-1 beta repressed the activation of the PI3K/Akt pathway, but ROS inhibition using N-acetylcysteine (NAC) rescued this pathway. The PI3K/Akt signaling suppression using LY294002 reversed the inhibitive effect of higenamine on IL-1 beta-caused apoptosis, and this effect was weakened by ROS inhibition. In conclusion, higenamine attenuates IL-1 beta-caused apoptosis of HNPCs via ROS-mediated PI3K/Akt pathway.

Automated summary

Higenamine can alleviate IL-1 beta-induced apoptosis of HNPCs through ROS-mediated PI3K/Akt pathway. Higenamine affects the expression of Bcl-2, Bax, and cleaved caspase-3, but has no impact on ROS levels and PI3K/Akt signaling.