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.

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

A recent study conducted by researchers shows that aspirin’s main breakdown product, salicylic acid, blocks HMGB1, which may explain many of the drug’s therapeutic properties. The findings appear in the journal Molecular Medicine.

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.

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-signaling proteins called cytokines.

Researchers not only confirmed that salicylic acid can bind to HMGB1, but also to identify the salicylic acid binding sites.The group identified two derivatives of salicylic acid, which are far more effective than salicylic acid in blocking HMBG1’s pro-inflammatory activities. They synthesized one compound in the lab, while a second was isolated from a licorice plant used as a Chinese medicinal herb.

“We’ve identified both synthetic and natural derivatives of salicylic acid which are 50 to 1000 times more potent than salicylic acid or aspirin in suppressing the pro-inflammatory activity of extracellular HMGB1,” said the author, “thereby providing proof of concept that more effective salicylic acid-based drugs are attainable.”

http://bti.cornell.edu/news/new-study-provides-key-insights-into-aspirins-disease-fighting-abilities/