About APPA
APPA is a patented fixed combination of two synthetically produced, synergistic, secondary metabolites of plant origin which exerts its anti-inflammatory effect through modulation of NF-κB and Nrf2 pathways.
Progress in osteoarthritis research has resulted in the identification of signaling pathways with potential mechanistic targets. It is evident that osteoarthritis is not solely a disease caused by ‘wear and tear’ of the joint rather a complex interplay between catabolic and anabolic effects of chondrocytes, which involves the entire joint.
Given the multiple pathways involved in this disorder, it is unlikely that targeting a single molecule by a specific mechanism will be effective at combating the disease. As with other chronic disorders, the future of osteoarthritis treatment may lie in combination therapy.
APPA [AKL4] is an investigational NFkB and Nrf2 modulator.
NF-κB is a key intracellular messenger that plays a central role in inflammation through its ability to induce transcription of proinflammatory genes.
Nrf2 is a factor that regulates gene transcription of anti-oxidants in thereby reducing damage by the reactive oxidant species (ROS) generated during inflammation.
NF-κB and Nrf2 activity is essential for maintaining coordinated cellular responses to resolve the inflammatory status of the cell/tissue.
In chronic pathologic states such as OA where there is an imbalance between the Nrf2 and NF-κB pathways a robust but fine-tuned NF-κB and Nrf2 response is essential for an appropriate inflammatory response and subsequent resolution.
By harmonizing the cross-talk between Nrf2 and NF-κB, APPA regulates rather than blocks the immune response, whilst maintaining host defences.