Hyperoside ameliorates TNFαinduced inflammation, ECM degradation and ER stressmediated apoptosis via the SIRT1/NFκB and Nrf2/ARE signaling pathways in vitro

Abstract

intervertebral disc degeneration (idd) is the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinalrelated disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits antiinflammation, antioxidation and antiapoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TnF)αinduced idd progression in human nucleus pulposus cells (nPcs) and its potential mechanism. The activity and apoptosis of nPcs were detected by cell counting Kit8 and flow cytometry analyses, respectively. The expression of interleukin (il)6 and il1β was detected with eliSa kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively allevi ated TnFαinduced nPc apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase2, il1β and il6 in TnFαstimulated nPcs. Compared with the findings in the TNFα group, the interven tion of hyperoside attenuated the upregulated expression of aggrecan and collagen ii, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disinte grin and metalloproteinase with thrombospondin motifs 5. in addition, hyperoside upregulated sirtuin1 (SirT1) and nuclear factor e2related factor 2 (nrf2) protein expression, and inhibition of SirT1 or nrf2 signaling reversed the protective effect of hyperoside on TnFαinduced nPcs. in summary, hyperoside ameliorated TnFαinduced inflammation, extracellular matrix degradation, and endoplasmic reticulum stressmediated apoptosis, which may be associated with the regulation of the SirT1/nFκB and nrf2/antioxidant respon sive element signaling pathways by hyperoside.