Ameliorative effect and potential mechanism of Ermiao san on adjuvant-induced arthritis in rats

Abstract

Purpose: To investigate the effect and mechanism of action of Ermiao san (EMS), a traditional Chinese herbal formula, on inflammation development and production of inflammatory mediators in adjuvant induced arthritis (AIA). Methods: AIA was induced by injection of 0.1 ml Freund’s complete adjuvant (FCA, 10 mg/ml) in the left hind footpad of the rats. AIA rats were intragastricly treated with 0.5, 1, 2 g/kg EMS or 0.1 g/kg methotrexate from day 7 to 28 after FCA challenge. Foot volume and histological score were measured. Osteoclast number was calculated by tartrate-resistant acid phosphatase (TRAP) staining assay. Levels of prostaglandin (PG) E2, tumor necrosis factor (TNF) -α and interleukin (IL)-1β in serum were determined by enzyme-linked immunosorbent assay (ELISA) while the level of nitric oxide (NO) in serum was analyzed by Griess reaction method. Results: Foot volume, histological score, osteoclast number and serum levels of TNF-α, IL-1β, PGE2 and NO were all increased in AIA group rats on day 28 after FCA challenge (all p < 0.01) compared with control. EMS (1 and 2 g/kg) significantly decreased the foot volume of AIA rats by 10% (p < 0.05) and 19% (p < 0.01), respectively, compared with AIA group. Furthermore, 1 and 2 g/kg EMS significantly reduced histological score by about 28% (p < 0.05) and 46% (p < 0.01), respectively, as well as osteoclast number by 12% (p < 0.05) and 15% (p < 0.05), respectively, compared with AIA group. In addition, 1 and 2 g/kg EMS significantly decreased the serum levels of TNF-α about 23% (p < 0.05) and 43% (p < 0.01), IL-1β by15% (p < 0.05) and 26% (p < 0.01), NO 13% (p < 0.05) and 26% (p < 0.01) as well as PGE2 by 11% (p < 0.05) and 15% (p < 0.01), respectively, compared with AIA group. Conclusion: These results suggest that EMS probably alleviates arthritis development and joint destruction by decreasing the production of inflammatory mediators in AIA rats.