Radix Salvia miltiorrhiza for Ankylosing Spondylitis: Determining Potential Inflammatory Molecular Targets and Mechanism Using Network Pharmacology

Abstract

Radix Salvia miltiorrhiza (RSM) is widely used for the clinical improvement of inflammatory diseases. However, the actions of RSM in the treatment of ankylosing spondylitis (AS) have not been fully explored. Therefore, this study was designed to use retrospective clinical data mining approach to understand the effects of RSM on AS-related immuno-inflammatory processes, use network pharmacology to predict therapeutic targets of RSM, and to further investigate the pharmacological molecular mechanism in vitro. RSM treatment has a long-term correlation with the improvement of AS-related immuno-inflammatory indicators through computational models. We established protein-protein interaction networks, conducted KEGG analysis to enrich significant TNF pathways, and finally obtained three core targets of RSM in the treatment of AS, namely, prostaglandin endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Screening of RSM active ingredients with node degree greater than 20 yielded cryptotanshinone and tanshinone IIA, and previous studies have reported their anti-inflammatory effects. In vitro, both cryptotanshinone and tanshinone IIA significantly inhibited the expressions of PTGS2, IL-6, and TNF-α in peripheral blood mononuclear cells in AS patients. In conclusion, cryptotanshinone and tanshinone IIA, which are the active components of RSM, may inhibit the activation of TNF signaling pathway in AS patients by downregulating the expression of PTGS2, IL-6, and TNF-α. These findings illustrate that RSM may be a promising therapeutic candidate for AS, but further validation is required.