Hyperoside ameliorates TNF-α-induced inflammation, ECM degradation and ER stress-mediated apoptosis via the SIRT1/NF-κB and Nrf2/ARE signaling pathways in vitro

Intervertebral disc degeneration (IDD) is the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinal-related disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits anti-inflammation, anti-oxidation and anti-apoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TNF)-α-induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The activity and apoptosis of NPCs were detected by Cell Counting Kit-8 and flow cytometry analyses, respectively. The expression of interleukin (IL)-6 and IL-1β was detected with ELISA kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively alleviated TNF-α-induced NPC apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, IL-1β and IL-6 in TNF-α-stimulated NPCs. Compared with the findings in the TNF-α group, the intervention of hyperoside attenuated the upregulated expression of aggrecan and collagen II, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5. In addition, hyperoside upregulated sirtuin-1 (SIRT1) and nuclear factor E2-related factor 2 (Nrf2) protein expression, and inhibition of SIRT1 or Nrf2 signaling reversed the protective effect of hyperoside on TNF-α-induced NPCs. In summary, hyperoside ameliorated TNF-α-induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress-mediated apoptosis, which may be associated with the regulation of the SIRT1/NF-κB and Nrf2/antioxidant responsive element signaling pathways by hyperoside.