Salvianolic Acid B Protects Intervertebral Discs from Oxidative Stress‐Induced Degeneration via Activation of the JAK2/STAT3 Signaling Pathway

Abstract

Objective. To evaluate the influence of salvianolic acid B (SAB), an antioxidant derived from Danshen, on intervertebral disc degeneration (IDD) and its possible molecular mechanisms. Methods. Sixty adult rats were randomly grouped (control, IDD, and SAB IDD groups). IDD was induced using needle puncture. The rats received daily administration of SAB (20 mg/kg) in the SAB IDD group while the other two groups received only distilled water. The extent of IDD was evaluated using MRI after 3 and 6 weeks and histology after 6 weeks. Oxidative stress was assessed using the ELISA method. In in vitro experiments, nucleus pulposus cells (NPCs) were treated with H2O2 (100 μM) or SAB+H2O2, and levels of oxidative stress were measured. Cell apoptosis was assessed by flow cytometry, expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins. Cell proliferation rate was assessed by EdU analysis. Pathway involvement was determined by Western blotting while the influence of the pathway on NPCs was explored using the pathway inhibitor AG490. Results. The data demonstrate that SAB attenuated injury-induced IDD and oxidative stress, caused by activation of the JAK2/STAT3 signaling pathway in vivo. Oxidative stress induced by H2O2 was reversed by SAB in vitro. SAB reduced the increased cell apoptosis, cleaved caspase-3 expression, and caspase-3 activity induced by H2O2. Reduced cell proliferation and decreased Bcl-2/Bax ratio induced by H2O2 were rescued by SAB. Additionally, the JAK2/STAT3 pathway was activated by SAB, while AG490 counteracted this effect. Conclusion. The results suggest that SAB protects intervertebral discs from oxidative stress-induced degeneration by enhancing proliferation and attenuating apoptosis via activation of the JAK2/STAT3 signaling pathway.

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

“…GSVA suggested that the gene sets highly correlated with IDD were associated with DNA repair, cell cycle, oxidative phosphorylation, IL-6-JAK-STAT3 signaling, and apoptosis. Among them, DNA repair and JAK-STAT3 signaling have been proved to be highly correlated with IDD ( Nasto et al, 2013 ; Dai et al, 2021 ). Mitochondria are the principal source of energy and ROS production in IVD cells.…”

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

“…Dai et al found that SAB slowed down the process of IDD and reconstructed the structure of IVD through in vivo experimental study. Subsequently, it was also confirmed that the levels of GSH and SOD2 in the degenerative IVD were reduced, and SAB treatment significantly reversed this change ( Dai S. et al, 2021 ). In additional in vitro experiments, SAB was found to reduce the levels of ROS and MDA and increase the levels of GSH and SOD2.…”

Natural Products of Pharmacology and Mechanisms in Nucleus Pulposus Cells and Intervertebral Disc Degeneration

“…Salvianolic acid is the most abundant polyphenolic of Salvia miltiorrhiza ; it exhibits anti-inflammatory, anticancer, antioxidant, and cardioprotective effects [ 78 ]. Dai et al [ 79 ] found that salvianolic acid B activated the JAK2/STAT3 signalling pathway, reduced ROS and MDA production, and upregulated GSH and SOD2 production to maintain mitochondrial function in NP cells. Transformation of the mesenchymal stem cells (MSCs) of IDD patients has attracted considerable attention.…”