Exp Ther Med 2019 May 12;17(5):3299-3306. Epub 2019 Mar 12.
Department of Emergency, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
The current study aimed to investigate the inhibitory effect of tanshinone IIA (Tan IIA) on the inflammatory response in patients with rheumatoid arthritis (RA) and explore its mechanism. A total of 50 patients with RA were randomly separated into the control group (15 cases) and the research group (35 cases). The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in serum were determined, and peripheral blood mononuclear cells (PBMCs) were separated from patients with RA and cultured . The effects of the β-arrestin 2 small interfering (si)RNA incubation, lipopolysaccharide (LPS) stimulation or Tan IIA incubation on TNF-α and IL-6 levels, and the expression levels of β-arrestin 2, NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and transcription factor p65 (p65) proteins were investigated. Prior to treatment, no significant differences in TNF-α and IL-6 levels in serum of patients with RA were identified between the research and control groups. Following treatment, the TNF-α and IL-6 levels in the serum of patients with RA in the research group were significantly lower compared with those in the research group prior to treatment and those in the control group following treatment (P<0.05). Tan IIA inhibited the LPS-induced secretion of TNF-α and IL-6, upregulated the LPS-inhibited expression of the β-arrestin 2 and SIRT1 proteins, and downregulated the LPS-induced expression of the p65 protein in the PBMCs of patients with RA. The β-arrestin 2 small interfering (si)RNA significantly upregulated the secretion of TNF-α and IL-6, inhibited the expression of the SIRT1 protein and upregulated the expression of the p65 protein in PBMCs of patients with RA. Tan II A effectively increased the weight of rats with rheumatoid arthritis, and reduced the circumference of the left posterior ankle, the posterior plantar metatarsal thickness, and the content of serum TNF-α and IL-6. Tan IIA did not significantly reverse these β-arrestin 2 siRNA-induced changes. Tan IIA inhibited the inflammatory response in PBMCs of patients with RA by upregulating β-arrestin 2 expression.