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.