Our old faithful wonder drug

How does Aspirin work its miracles?

From: Rutgers University

A research team that includes a Rutgers professor has found that the main ingredient in aspirin targets the activities of an inflammatory protein associated with a wide variety of diseases. The discovery offers hope for the development of more powerful aspirin-like drugs. 

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.

A recent study led by researchers at the Cornell University-affiliated Boyce Thompson Institute (BTI) in collaboration with colleagues at Rutgers and Italy’s San Raffaele University and Research Institute, shows that aspirin’s main breakdown product, salicylic acid, blocks the protein, HMGB1, which could explain many of the drug’s therapeutic properties.

The findings appear Sept. 23, 2015, in the journal Molecular Medicine.

“We’ve identified what we believe is a key target of aspirin’s active form in the body, salicylic acid, which is responsible for some of the many therapeutic effects that aspirin has,” said senior author Daniel Klessig, a professor at BTI and Cornell University. “The protein, HMGB1, is associated with many prevalent, devastating diseases, including rheumatoid arthritis, heart disease, sepsis and inflammation-associated cancers, such as colorectal cancer and mesothelioma,” he said.

Aspirin’s pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce hormone-like compounds that cause inflammation and pain—a discovery that netted its discoverer, John Vane, a Nobel prize. 

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 effects as aspirin, suggesting that salicylic acid may interact with additional proteins.

“Some scientists have suggested that salicylic acid should be called ‘vitamin S’, due to its tremendous beneficial effects on human health, and I concur,” said lead author Hyong Woo Choi, a research associate at BTI.

In the current 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 characterized.

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.

Read more at Rutgers University.