Salvia miltiorrhiza injection restores apoptosis of fibroblast-like synoviocytes cultured with serum from patients with rheumatoid arthritis

Abstract

Salvia miltiorrhiza injection (SMI) is a watersoluble agent, derived from Salvia miltiorrhiza (SM), that is traditionally used to treat cardiovascular and cerebrovascular diseases. Furthermore it has been demonstrated to possess the ability to induce apoptosis of tumor cells. However, it remains unclear whether SMI can induce apoptosis of rheumatoid arthritis (RA) fibroblastlike synoviocytes (FLS), which are hyperplastic in RA due to defective apoptosis. There is also evidence that allogenic serum may be associated with the induction of apoptosis. The aim of the present study was to investigate the involvement of serum during SMIinduced apoptosis in RA FLS. The results demonstrated that SMI could induce apoptosis of RA FLS, cultured with fetal bovine serum (FBS), in a dosedependent manner. In addition, SMI decreased the expression of nuclear factorB in RA FLS nuclear extracts and inhibited the secretion of tumor necrosis factor. Fas ligand expression was not detected in RA FLS, in either the presence or absence of SMI. The proapoptotic genes Bcell lymphoma 2 (Bcl2) associated X protein (Bax) and Fas, were shown to be upregulated following SMI stimulation, whereas the expression levels of the antiapoptotic gene Bcl2, were downregulated. Upon replacement of FBS with normal human serum, the apoptotic rate and Bax mRNA expression levels following SMI stimulation, were unchanged. However, culturing RA FLS with patient' serum (RPS), restored the apoptotic rate and Bax mRNA expression levels following SMI stimulation. There may be numerous mechanisms by which SMI inhibits RA FLS proliferation. The present study demonstrated that SMI can restore apoptosis of RA FLS cultured with RPS. These results indicate that SMI may have a potential role in the treatment of synovial hyperplasia of RA.