The antioxidant Glycitin protects against intervertebral disc degeneration through antagonizing inflammation and oxidative stress in nucleus pulposus cells

Abstract

Intervertebral disc degeneration (IVDD) is a kind of typical degenerative disorder of the skeletal muscle system caused by many factors including aging, abnormal mechanical stress and inflammatory responses. Glycitin is a natural isoflavone extracted from legumes. Previous studies have found that it is anti-inflammatory and promotes wound repair. However, the role of Glycitin in IVDD has not been elucidated. In the present research, we were surprised that Glycitin antagonized the NF-κB pathway activity. In addition, we also found that Glycitin alleviated TNF-α-induced metabolic disorders, extracellular matrix degradation, oxidative stress, inflammation responses, and mitochondrial damage. Furthermore, in in vivo experimental study, we discovered Glycitin attenuated IVDD. The results revealed that Glycitin alleviated the degenerative phenotype of IVDD. According to this research, Glycitin has anti-inflammatory properties that might exert a protective function in IVDD, suggesting a prospective therapeutic approach for IVDD.

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

“…Even though in these cases the conferred protective effects have not been tested for their association with a senotherapeutic action in the IVD thus far, anti-oxidant, anti-inflammatory and anti-catabolic properties have been described for them, rendering them ideal candidates in the pursuit of novel senomorphics for the particular tissue. For example, (i) baicalein has been shown to inhibit IL-1β-induced inflammatory response and ECM degradation in rat NP IVD cells in vitro and to attenuate IDD in vivo [ 262 ], as well as to alleviate TNF-α-induced MMP-2 and -9 up-regulation in human NP IVD cells [ 263 ]; (ii) berberine has been shown to inhibit the TBHP-induced production of ECM-degrading enzymes in rat NP IVD cells in vitro and to prevent the development of IDD in a needle puncture-induced rat model [ 264 ]; (iii) celastrol has been reported to suppress IL-1β-stimulated up-regulation of COX-2, IL-6, PEG2 and MMP-13 in rat chondrocytes in vitro and to delay the progression of cartilage damage in an OA rat model [ 265 ], to play an anti-inflammatory role in rheumatoid arthritis and to suppress the expression of MMP-1, -3 and -13, COX-2, iNOS and HSP90β in primary human OA chondrocytes [ 266 , 267 ], to reduce the production of inflammatory mediators preventing the destruction of articular cartilage after intra-articular injection in a MIA-induced knee OA rat model [ 268 ], to reduce IL-1β-induced ECM catabolism, oxidative stress and inflammation in human NP IVD cells and to attenuate rat IDD in vivo [ 269 ] and most importantly to be able to target multiple genes involved in cellular senescence in OA based on a comparative transcriptomics and network pharmacology analysis [ 270 ]; (iv) chlorogenic acid has been reported to mitigate cartilaginous endplate degeneration and to postpone IDD development in a lumbar spine instability IDD mouse model [ 271 ]; (v) glycitin has been reported to antagonize TNF-α-induced cartilage degeneration and inflammation in primary mouse chondrocytes and TNF-α-induced inflammatory response and ECM catabolism in human NP IVD cells in vitro, while its intraperitoneal administration rescued tissue destruction in an anterior cruciate ligament transection OA mouse model and a puncture-induced IDD rat model [ 272 , 273 ]; (vi) higenamine has been shown to attenuate IL-1β-induced elevation of ROS levels, inflammatory mediators and catabolic markers in human NP IVD cells [ 274 , 275 ]; (vii) mangiferin treatment has been shown to decrease proliferation, migration and secretion of inflammatory cytokines and MMPs and to promote apoptosis of fibroblast-like synoviocytes in vitro, as well as to alleviate arthritis index, to down-regulate the production of inflammatory mediators and ECM-degrading enzymes and to ameliorate oxidative stress in the plasma and the synovial tissue in an adjuvant-induced arthritis rat model [ 276 ]. Furthermore, mangiferin has been reported to attenuate ...…”