Beyond Headache Relief

A team from USC Dornsife and Harvard University has uncovered a key biological mechanism that makes aspirin and omega-3 fatty acids effective at reducing inflammation.

Doctors have long prescribed aspirin together with a diet rich in omega-3s as a way to reduce inflammation caused by the body’s own immune system, which can exacerbate heart disease, lung and kidney disease, as well as arthritis and cancer, among other ailments.

Thanks to research led by Nicos Petasis, the Harold and Lillian Moulton Chair in Chemistry and professor of chemistry and pharmacology in USC Dornsife, and Charles Serhan of Harvard, now they know why.

Studying inflammation in mice, the team determined that aspirin triggers the production of a new form of molecules called resolvins, which are naturally made by the body from omega-3 fatty acids to shut off inflammation. In particular, Serhan found that one type of resolvin — resolvin D3 — lingers at the site of inflammation, suggesting that it plays a particular role in helping to conclude this immune process.

After making its discovery, the team explored the structure of resolvin D3 to better understand why and how it works to shut off inflammation.

“Aspirin is able to modify an inflammatory enzyme to stop forming molecules that propagate inflammation and instead produce molecules from omega-3 fatty acids, like resolvin D3, that help inflammation to end,” said Petasis, who has joint appointments at the USC School of Pharmacy and the USC Norris Comprehensive Cancer Center. “We were able to produce by chemical synthesis both resolvin D3 and aspirin-triggered resolvin D3 in pure form that allowed us to establish their complete structures and biological activities.”

Serhan, of Brigham and Women’s Hospital and Harvard Medical School, added: “We also identified the human receptor that is activated by resolvin D3, which is critical in understanding how resolvin D3 works in the body to resolve inflammation. With this information, other investigators will now also be able to study the pro-resolving actions and anti-inflammatory properties of resolvin D3.”

Nicos Petasis, the Harold and Lillian Moulton Chair in Chemistry and professor of chemistry and pharmacology in USC Dornsife, led the research with a collaborator from Harvard Medical School. Photo by Alexandra Bissonnette.

The research by Petasis and Serhan was recently published in Chemistry & Biology. Other co-authors of the paper included Jeremy Winkler, a Ph.D. student in USC Dornsife; and Jesmond Dalli, Romain Colas, Hildur Arnardottir, Chien-Yee Cheng and Nan Chiang of Harvard.

Now that the mechanism behind omega-3s and aspirin treatment is better understood, future research by the teams of Petasis and Serhan will focus on determining which other diseases might best be treated by natural anti-inflammatory molecules.

The research was funded by the National Institutes of Health (grant P01GM095467). It is the latest joint effort of a 20-year research collaboration among the research teams.

Serhan and Petasis are inventors on patents (resolvins) assigned, respectively, to Brigham and Women’s Hospital and USC, and licensed for clinical development to Resolvyx Pharmaceuticals. As scientific co-founders of Resolvyx, the researchers own equity in the company.