Luteolin suppresses TNF‑α‑induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF‑κB pathway

Abstract

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.

[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

“…A previous investigation indicated that luteolin might act on TNF and medicate the HIF-1 pathway implicated in the treatment of HUA [14]. Recent research has indicated that luteolin can effectively reduce the expression of proinflammatory factors IL1B and IL-6 to mitigate TNF-α-induced cellular inflammatory injury [72]. Rutaecarpine, an alkaloid extracted from the unripe fruit of E. rutaecarpa, possesses an antiinflammatory function [73].…”

Luteolin induces ferroptosis in prostate cancer cells by promoting TFEB nuclear translocation and increasing ferritinophagy

“…Luteolin, a natural plant extract, has demonstrated various biological and anticancer effects. 27 In this study, we treated PCa cells with luteolin in vitro and constructed lentiviral sh-TFEB cell lines to explore the effects of luteolin and TFEB on PCa. Our findings revealed that luteolin-induced ferroptosis in PCa cells by promoting TFEB nuclear translocation and enhancing ferritinophagy.…”

“…Research and development of new antitumor mechanisms and stable drugs are urgently needed. Luteolin, a natural plant extract, has demonstrated various biological and anticancer effects 27 . In this study, we treated PCa cells with luteolin in vitro and constructed lentiviral sh‐TFEB cell lines to explore the effects of luteolin and TFEB on PCa.…”

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

“…In TNF‐α induced NPC inflammatory stress experiment, the nuclear translocation of NF‐κB p‐p65 protein increased, the apoptosis markers Bax, Caspase 3, apoptosis protease activating factor 1 (Apaf1), and aging related proteins p16, p21, and p53 were upregulated, and the expression of antiapoptosis protein Bcl‐2 was downregulated. These changes accelerated cell senescence and apoptosis, and the nuclear translocation of p65 may be mediated by TRIM14 (Chen, Li, et al, 2022; Xie et al, 2022; Zhang, Tong, et al, 2021; Zhu et al, 2019).…”