Sodium Tanshinone IIA Sulfonate Ameliorates Injury‐Induced Oxidative Stress and Intervertebral Disc Degeneration in Rats by Inhibiting p38 MAPK Signaling Pathway

Abstract

Objective. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a representative traditional Chinese medicine. The aim of the study was to investigate the capability of STS to reverse injury-induced intervertebral disc degeneration (IDD) and explore the potential mechanisms. Methods. Forty adult rats were randomly allocated into groups (control, IDD, STS10, and STS20). An IDD model was established by puncturing the Co8-9 disc using a needle. Rats in the STS groups were administered STS by daily intraperitoneal injection (10 or 20 mg/kg body weight) while rats in the control and IDD groups received the same quantity of normal saline. After four weeks, the entire spine from each rat was scanned for X-ray and MRI analysis. Each Co8-9 IVD underwent histological analysis (H&E, Safranin-O Fast green, and alcian blue staining). A tissue was analyzed by immunohistochemical (IHC) staining to determine the expression levels of collagen II (COL2), aggrecan, matrix metalloproteinase-3/13 (MMP-3/13), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Levels of oxidative stress were measured using an ELISA while activity of the p38 MAPK pathway was assessed using Western blot analysis. Results. Compared with the control group, needle puncture significantly decreased IVD volume and T-2 weighted MR signal intensity, confirming disc degeneration. These alterations were significantly attenuated by treatment with 10 or 20 mg/kg STS. Lower COL2 and aggrecan and higher MMP-3/13, IL-1β, IL-6, and TNF-α levels in the IDD group were substantially reversed by STS. In addition, treatment with STS increased antioxidative enzyme activity and decreased levels of oxidative stress induced by needle puncture. Furthermore, STS inhibited the p38 MAPK pathway in the rat model of IDD. Conclusions. STS ameliorated injury-induced intervertebral disc degeneration and displayed anti-inflammatory and antioxidative properties in a rat model of IDD, possibly via inhibition of the p38 MAPK signaling pathway.

The role of oxidative stress in intervertebral disc cellular senescence

“…AQP-3 could inhibit the expression of Bax and caspase-3 genes and alleviate NP cells’ apoptosis under oxidative damage. The inhibition of the p38 MAPK pathway by STS and AQP-3 has implications in further applications for alleviating the development of DDD ( 125 , 126 ).…”

TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo

“…Apoptosis is initiated and executed by the caspase family of cysteine proteases located in the cytosol. The overexpression of Bcl-2 and the knockdown of caspase3 both prevent apoptosis and degenerative changes [ 35 , 36 ]. Following the treatment with TAK-715, Bcl-2 expression significantly increased, but Bax and cleaved-caspase3 expression decreased.…”

Roles of p38 MAPK signalling in intervertebral disc degeneration

“…The expression levels of p38α and p38β were remarkably higher in the IVDD tissue compared with that in the normal NP tissue, while the expression level of p38δ was lower in the IVDD tissue compared with that in the normal NP tissue and could only be detected in half of the IVDD tissue; further, the expression level of p38γ was lower than that of p38δ. In vivo, Dai et al 42 showed that the expression level of the activated p38 MAPK was significantly higher in the rat IVDD groups compared with the control group ( p < 0.01). Cheng et al 43 found a significant increase in the expression level of activated p38 in degenerated rat NP tissues.…”