Sparstolonin B prevents lumbar intervertebral disc degeneration through toll like receptor 4, NADPH oxidase activation and the protein kinase B signaling pathway

Abstract

Intervertebral disc degeneration (IVDD) is the most common pathogeny of lumbago. It is the pathological basis for a series of spinal degenerative diseases. For a long time, the diagnosis and treatment of lumbago have rendered difficult, since the pathogeny has not been identified. Therefore, the present study aimed to investigate the protective effect of Sparstolonin B in preventing lumbar intervertebral disc degeneration, and explored its potential mechanism in rats. Firstly, Sparstolonin B effectively reduced the histological score of disc degeneration and increased endplate porosity of L2 superior endplates in a lumbar IVDD rat model. Sparstolonin B significantly inhibited the IVDD‑induced inflammatory factors tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6, oxidative stress factors (malondialdehyde), and superoxide dismutase and caspase‑3/9 activities. Treatment with Sparstolonin B significantly suppressed toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor (NF)‑κB protein expression, inhibited NAPDH oxidase 2 protein expression and induced phosphoinositide 3‑kinase and phosphorylated protein kinase B protein expression in the IVDD rat model. These results demonstrated that Sparstolonin B prevents lumbar IVDD‑induced inflammation, oxidative stress and apoptosis through TLR4/MyD88/NF‑κB, NADPH oxidase activation and the phosphoinositide 3‑kinase/protein kinase B signaling pathway. These results implicate Sparstolonin B for use as a therapeutic agent for IVDD in clinical applications.

Effects of the NF‑κB/p53 signaling pathway on intervertebral disc nucleus pulposus degeneration

“…Therefore, the present study suggested that the NF-κB signaling pathway regulated the expression of cytokines via p53. A previous study reported that sparstolonin B prevents lumbar IDD-induced inflammation, oxidative stress and apoptosis via the toll-like receptor 4/MyD88/NF-κB signaling pathway ( 52 ). Furthermore, small ubiquitin like modifier 2 gene silencing inhibits nucleus pulposus cell apoptosis and senescence in a rat model of IDD by downregulating the p53 signaling pathway ( 22 ).…”

Toll‐like receptor involvement in adolescent scoliotic facet joint degeneration

“…As TLR expression is elevated and the chondrocytes are strongly responsive to alarmins in scoliotic cartilage blocking their activity could potentially modify disease progression. To assess the effect of blocking TLR activation, two naturally derived compounds that prevent the recruitment of MyD88 to the TIR domain of TLRs, and thus TLR signalling, were used 31,41 . The antagonists did not significantly modulate gene expression in scoliotic chondrocytes challenged with biglycan (Figure 4A,B).…”

“…To assess the effect of blocking TLR activation, two naturally derived compounds that prevent the recruitment of MyD88 to the TIR domain of TLRs, and thus TLR signalling, were used. 31,41 The antagonists did not significantly modulate gene expression in scoliotic chondrocytes challenged with biglycan ( Figure 4A,B).…”

“…Two such molecules are o-Vanillin and Sparstolonin B which interfere with MyD88 recruitment preventing downstream signalling. [29][30][31] This study is focused on evaluating a potential involvement of the TLRs in AIS facet joint OA and evaluating the potential of inhibiting TLRs using small-molecule inhibitors as potential disease-modifying therapeutics. were collected, and samples taken for histology as described below.…”

“…There has been a recent interest in using small‐molecule inhibitors to block TLR activation. Two such molecules are o‐Vanillin and Sparstolonin B which interfere with MyD88 recruitment preventing downstream signalling 29‐31 …”