Anti-inflammatory Activity And Mechanism Of A Novel Non-steroidal Anti-inflammatory Drug AC-8

The gastrointestinal adverse reactions and the other side effects of traditional non-steroidal anti-inflammatory drugs limits its application in clinical. Development of new NSAIDs becomes a research focus in the future. Based on the combination principles, we synthesis a new compound AC-8 which has strong anti-tumor effects in preliminary studies. To further evaluate the market potential of AC-8, the experiment explored the effect of gastrointestinal tolerability and anti-inflammatory effect of AC-8 in vivo and explored the anti-inflammatory mechanism of AC-8.We evaluated the gastrointestinal tolerability and anti-inflammatory effect of AC-8 using the rat gavage experiment and the mouse ear swelling model respectively. Elisa kit, PCR and Western Blot experiments were used to determine the expressions of TNF-a, IL-1β, COX-2, NF-κB and MAPK.The results showed that the gastrointestinal adverse effects of AC-8 were minimal and the anti-inflammatory effects were significant in vivo. AC-8 inhibited expressions of COX-2, TNF-a and IL-1β in a concentration-dependent manner in vitro. AC-8 blocked expressions of nuclear transcription factor NF-κB and mitogen-activated protein kinase MAPK. These findings explained the significant anti-inflammatory effect of AC-8 and helped us to assess the market potential of AC-8 too.This study found that AC-8 has minimal gastrointestinal adverse reactions and significant anti-inflammatory effects in vivo. The inhibitions of COX-2, TNF-a and IL-1β may explain the significant anti-inflammatory effect of AC-8 in vivo. And the suppression of NF-κB showed the molecular mechanism under which AC-8 inhibited expressions of COX-2 and Cytokines.The study also prompted the link between MAPK and NF-κB that both play a regulatory role in the initiating and maintaining the process of inflammation.