Most supplements that have effects on our immune system also tend to have positive effects on inflammation, and so not surprisingly, Andrographis also has some fairly pronounced effects on inflammation! These effects extend mostly towards pain management and Andrographis appears to have fairly significant pain management support effects. Unlike other supplements that help promote balanced levels of inflammation and pain management, Andrographis works on more upstream mechanisms. Most inflammation-balancing compounds act on cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. COX-2, in particular, is highly involved in pain because it triggers the synthesis of a compound called Prostaglandin E2 (PGE-2). PGE-2 is involved in the perception of pain. To explain this, we have to take a brief deep dive into a bit of science!
Pain is, in many ways, a warning mechanism to tell us something is not completely right in our bodies. It is a neurological signal that actually makes us perceive this pain. PGE-2 can bind to two different receptors: Prostaglandin E2 receptor 1 (EP1) and Prostaglandin E2 receptor 4 (EP4). When PGE-2 binds to either EP1 or EP4, it increases the excitability of our peripheral nerve endings through cation channels and by slowing the activity of hyperpolarizing potassium channels. This increase in excitability then makes it more likely that our peripheral nerve endings will send out pain signals to the brain, which is what eventually leads to us perceiving a feeling of pain. By regulating the activity of COX-2, we can support lower levels of PGE-2 synthesis, thereby supporting pain management. However, let’s move upstream a bit more!
Upstream from COX-2, we find another enzyme called Interleukin-2 (IL-2). This particular enzyme controls the expression of COX-2. Thus, regulating the activity of IL-2 can also regulate the expression of COX-2. Putting two and two together, this means that lower IL-2 activity is correlated with lower COX-2 activity. Thus, regulating IL-2 may help support pain management. However, let’s move upstream further yet again! From IL-2, we have one other enzyme called nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). NF-κB can be seen as the master regulator here. This is because NF-κB controls the activity of IL-2, COX-2, and PGE-2 synthesis. This is where Andrographis paniculata exerts its effect. Yet, it gets even a little bit more complex!
When compared to other compounds that regulate the activity of NF-κB, Andrographis paniculata had a superior pain management effect. This means that it is likely that Andrographis paniculata also signals through another NF-κB related pathway separate from the IL-2 -> COX-2 -> PGE-2 system. This system has not yet been identified by researchers studying the effects of Andrographis, but it has been proposed and indicates that the pain management effects of Andrographis may be quite comprehensive!