Scientists Just Learned Something New About How Aspirin Works

We still have a lot to learn about one of the world’s oldest medicine: aspirin. To research out this week, researchers said they have discovered more about how the drug reduces inflammation. The findings may plead to the creation of similar but safer treatments for inflammation and possibly cancer, according to the team.

Also known as acetylsalicylic acid, aspirin is first synthesized by the end of the 20th century, even a precursor of it—derived from willow plants—became used by humans for thousands of years. It is a type of nonsteroidal anti-inflammatory drug (NSAID), and, llike other NSAIDs, it can treat fever, inflammation, and pain. This there is also a unique effect of reducing blood.

Aspirin remains one of the most widely used drugs in the world, both as a short-term option for various ailments and as a preventive treatment for people at high risk of cardiovascular disease. But it is not without side effects—especially an increased risk of gastrointestinal bleeding. Last year, even the experts in the US stop recommending a daily dose of baby aspirin for adults without a history of heart attack or stroke, citing evidence that any modest benefit for the average person would be outweighed by known risks.

Importantly because aspirin has been around for over a century, we still don’t understand much about what it does inside our bodies. So scientists at the University of Texas at Arlington wanted to better study its mechanics. Their findings were presented Tuesday at the annual meeting of the American Society for Biochemistry and Molecular Biology (ASBMB), which will be held this week.

“Aspirin is a magic drug, but its long-term use can cause adverse effects such as internal bleeding and organ damage,” said study author Subhrangsu Mandal, a professor of chemistry and biochemistry, in a statement from ASBMB. “It’s important that we understand how it works so we can make safer drugs with fewer side effects.”

Aspirin is known to inhibit enzymes called cyclooxygenase, or COX. These enzymes play an important role in the production of other chemicals that cause inflammation. The researchers say they have discovered several ways that aspirin influences this process, from controlling transcription factors that allow the expression of cytokines (proteins involved in inflammation and our immune response) to slowing down the breakdown of amino acid tryptophan, another important player in inflammation. It also seems to do the latter by inhibiting the production of indoleamine dioxygenases (IDOs), particularly IDO1, during the inflammatory process.

“Since aspirin is a COX inhibitor, this suggests a potential interplay between COX and IDO1 during inflammation,” Mandel said.

This interplay could be important for treating other types of pain beyond the usual indications for aspirin, the researchers said. They note that some immunotherapy treatments, which try to boost the immune system’s response to cancer, also target IDO1. It is therefore possible that future COX/IDO1 inhibitors may become feasible as immunotherapy drugs.

This kind of basic research is important for drug development, but still the very beginning of the road. Mandel and his team say they are now trying to create small molecules in the lab that both inhibit COX/IDO1, which they will test as potential anti-inflammatory and immunotherapy drugs.