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Researchers have found how aspirin works in the body to target an inflammatory protein linked to a variety of diseases, such as rheumatoid arthritis, heart disease, and certain cancers.
Aspirin is one of the oldest and most commonly used medicines, but many of its beneficial health effects have been hard for scientists and physicians to explain.
The new study conducted by researchers at the Boyce Thompson Institute (BTI) and Rutgers University in US and San Raffaele University and Research Institute in Italy, shows that salicylic acid, an active metabolite of aspirin, blocks HMGB1, which may explain many of the drug's therapeutic properties.
"This protein, HMGB1, is associated with many prevalent, devastating diseases in humans, including rheumatoid arthritis, heart disease, sepsis and inflammation-associated cancers, such as colorectal cancer and mesothelioma," said senior author Daniel Klessig, a professor at BTI and Cornell University.
Aspirin's pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce prostaglandins - hormone-like compounds that cause inflammation and pain.
However, the body rapidly converts aspirin to salicylic acid, which is a much less effective inhibitor of cyclooxygenase 1 and 2 than aspirin.
Nonetheless, it has similar pharmacological effects as aspirin, suggesting that salicylic acid may interact with additional proteins.
In the study, researchers discovered the interaction between salicylic acid and HMGB1 by screening extracts prepared from human tissue culture cells to find proteins that could bind to salicylic acid.
They identified one of these proteins as HMGB1. These screens have also identified a key suspect in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, plus approximately two dozen additional candidates that have yet to be characterised.
In the body, HMGB1 is normally found inside the nucleus, but can enter the blood stream when released from injured tissues or secreted by certain immune or cancer cells.
The protein in the blood stream triggers inflammation by recruiting immune cells involved in preventing infections and repairing damaged tissues.
HMGB1 also activates these recruited immune cells to express genes that code for pro-inflammatory cell-signalling proteins called cytokines.
Using assays that measured the effects of salicylic acid on the recruitment and activation of immune cells, they showed that salicylic acid could block both of these functions at concentrations similar to those found in people on low-dose aspirin.
The study was published in the journal Molecular Medicine.
