Combined treatment with low dose prednisone and escin improves the anti-arthritic effect in experimental arthritis

Abstract

The present study was aimed at investigating whether low dose oral prednisone combined with escin could inhibit the progression of adjuvant-induced arthritis (AIA) in rats. Adjuvant arthritis was induced in SD rats began day 1 for 28 days. Prednisone at doses of 2, 10 mg/kg/day alone or escin at doses of 5, 10 mg/kg/day alone, or prednisone at dose of 2 mg/kg/day with escin at doses of 5 or 10 mg/kg/day were given to different groups of rats intragastrically from day 13 to 28 respectively. Paw swelling, arthritic index, histological and radiographic changes were assessed to evaluate the anti-arthritic effect. Weight growth, spleen and thymus indexes were also calculated. Serum samples were collected for estimation of pro-inflammatory cytokines. Rats developed erosive arthritis of the hind paw when immunized with adjuvant. Prednisone 2 mg/kg combined with escin 5 or 10 mg/kg significantly inhibited the paw swelling. Histopathological and radiographic analysis showed a marked decrease of synovial inflammatory infiltration, synovial hyperplasia and bone erosion by combination therapy, which also markedly suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). No significant changes were found in monotherapy group except prednisone 10 mg/kg group. Furthermore, combined treatment rescued some of GCs' adverse effects evidenced by increase in body weight and decrease in index of spleen compared with untreated AIA rats. In conclusion, the combination therapy possessed synergistic anti-arthritic efficacy and reduced adverse effect, which may play a role in the management of human RA.

Keywords: Adjuvant arthritis; Combined treatment; Escin; Inflammatory cytokine; Low dose prednisone; Synergistic effect.