Important new evidence on the mode of action of APPA

Previous work has shown that the anti-inflammatory effects seen with APPA results from upregulation of Nrf-2 and reduction of NF-kB activity (see news item Summary of Effects of APPA on Neutrophils).

Harmonisation of the molecular cross-talk between these intracellular messengers is known to reduce the levels of COX-1 and COX-2, enzymes that are inhibited by NSAIDs and thought to be involved in NSAIDs’ side effect profiles including heart failure (see news item BMJ: Painkillers linked to increased risk of heart failure) and gastric bleeding (see BMJ: Non-steroidal anti-inflammatory drugs and gastrointestinal damage).

New research with APPA has shown that COX-1 and COX-2 are not inhibited even at levels in excess of those found with high doses of the combination. These findings suggest that APPA would be unlikely to be associated with the GI side effects commonly seen with NSAIDs.