Puerarin is a major active ingredient extracted from the root of P. lobata, a traditional Chinese herb, and possesses anti-oxidative and anti-inflammatory activities. However, the low oral bioavailability of puerarin limits its further application. Therefore, we synthesized tetraacetyl puerarin (4AC) through acetylation to improve its liposolubility and bioavailability. In the present investigations, we tested the anti-oxidative and TNF-alpha suppressive activity of 4AC in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and bovine type 11 collagen-induced arthritic (CIA) rats. The results showed that 4AC retained the bioactivity of puerarin. And 4AC significantly increased the activity of SOD and reduced the level of MDA both in vitro and in vivo. It also improved the level of GSH-PX and the total antioxidant capacity in vivo. Furthermore, it dramatically decreased TNF-alpha level in the cultured supernatant of RAW264.7 cells treated with LPS and in the serum of CIA rats. These initial results indicated that 4AC had a potential therapeutic effect on CIA rats through an antioxidative and TNF-alpha suppressive activity. In addition, the molecular mechanism of anti-oxidation of 4AC was explored by testing the MAPKs/NF-kappa B signaling pathway. The results showed that 4AC significantly inhibited NF-kappa B expression and down-regulated the levels of p-ERK and p-JNK in LPS-activated RAW264.7 cells. These results indicated that 4AC had bioactive anti-oxidative effects and suggest the potential value of 4AC for the treatment of rheumatoid arthritis. (C) 2011 Elsevier B.V. All rights reserved.