Exploitable Potential for Many Treatments

Newswise — People have used aspirin to treat pain, fever and inflammation for more than a century, and the drug is also used to reduce the risk of strokes, heart attacks and some cancers. An estimated 100 billion aspirin tablets are taken worldwide each year, but how it works is still only partially understood.

Dan Klessig, a faculty member at Boyce Thompson Institute, has long suspected that aspirin’s broad effects are due in part to its primary metabolite, salicylic acid (SA). He reached this conclusion because humans metabolize aspirin into SA within minutes, and for nearly 50 years synthetic SA was used to treat pain, fever and inflammation before the advent of aspirin.

Moreover, for millennia many cultures throughout the world have treated pain, fever and inflammation with SA-rich plants — such as willow, meadowsweet and poplar — and continue to do so today.

In order to find clues as to how the compound works, Klessig led a group of researchers to identify human proteins that bind to SA and have their activity altered as a result. The BTI team also created a detailed network that links the newly discovered SA-binding proteins to dozens of human diseases, such as Alzheimer’s disease, Type II diabetes and arthritis.

The results, published in Scientific Reports in September, offer drug and nutraceutical developers a roadmap with multiple avenues for future research on new targets of aspirin and SA, and on novel, more potent synthetic or natural plant-derived SA derivatives.

“There are more potent derivatives of SA that could be made, as well as some present in medicinal plants such as licorice, that have the potential to treat a host of diseases,” Klessig said. “I think there is such untapped wealth here.”

First author Hyong Woo Choi agrees. “Based on our current research, SA might have effects on several developmental, neurological, psychiatric, ophthalmological and muscular diseases, as well as on cancer,” he said.

The team’s research was an outgrowth of three decades of work by Klessig, beginning with his 1990 Science paper describing how plants produce SA to protect themselves from viral infections and other pathogens.

“All plants contain SA, and plant-based diets result in almost as much SA in the body as taking a baby aspirin each day,” says Klessig. “We evolved eating plants, so it’s not surprising that SA affects our physiology.”

 

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