Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence β-galactosidase staining was used to detect the activity levels of β-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1β and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.

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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.