Tweaking aspirin’s ability to block a disease-linked protein could help treat devastating diseases.
Aspirin has been sold over-the-counter for more than a century, and millions of people have gulped it down to relieve headaches, muscle pains, and fever. In recent years, even more health benefits for this drug, technically known as acetylsalicylic acid, have been documented — including aspirin’s ability to lower the risk of heart disease when taken daily in small doses. A National Cancer Institute study suggests a daily aspirin could slash the risk of ovarian cancer by 20 percent, too. And a University of Oxford study of over 17,000 cancer patients found evidence daily aspirin lowers the risk malignancies will spread to other parts of the body.
Now there’s research from investigators at Cornell’s Boyce Thompson Institute (BTI), Rutgers University, and San Raffaele University and Research Institute, indicating aspirin could play an important role in not only preventing but also treating some of the most dreaded diseases of the 21st century.
Many of the recognized effects of aspirin on health haven’t been easy to explain. Doctors and scientists have mostly assumed the drug’s benefits are due to its ability to soothe inflammation and pain by blocking enzymes (known as cyclooxygenase 1 and 2) that produce prostaglandins, fatty acid compounds that have diverse hormone-like effects on the body.
However, when you take aspirin, your body rapidly breaks down the drug into salicylic acid, which doesn’t inhibit cyclooxygenase 1 and 2 as strongly as the acetylsalicylic acid form of the drug. So the Cornell-led research team reasoned salicylic acid was probably interacting with other additional substances in the body to produce the myriad therapeutic effects associated with aspirin.
By screening extracts prepared from human tissue culture cells to find proteins that bind to salicylic acid, the researchers found salicylic acid blocks a specific inflammatory protein, known as HMGB1. And, it turns out, HMGB1 is believed to play a role in devastating diseases including Alzheimer's and Parkinson's, colorectal cancer, mesothelioma, rheumatoid arthritis, heart disease, sepsis (a complication of an infection that triggers potentially life-threatening inflammatory responses), and a host of other serious conditions.
Tweaking salicylic acid’s power to block HMGB1 could potentially create powerful aspirin-like drugs to treat these serious health problems, according to the researchers.
Although HMGB1 is normally found inside the nucleus of cells, injured cells release it into the bloodstream, and it’s also secreted by certain immune and cancer cells. The result is inflammation and the triggering of more inflammation-causing proteins called cytokines.
Daniel Klessig, PhD, a professor at BTI and Cornell University, and Marco Bianchi of San Raffaele University and Research Institute used assays to show that salicylic acid in concentrations about the same as you’d get in a low-dose aspirin can block HMGBI, putting the brakes on the protein’s activation of inflammation.
"We've found that HMGB1 is involved in countless situations where the body confronts damage to its own cells, which occur in many disease conditions. In retrospect, it's almost obvious that a very general anti-inflammatory compound blocks a very general inflammation trigger," said Bianchi, who originally discovered that HMGB1 triggers inflammation.
"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 BTI researcher Hyong Woo Choi, PhD.
Although taking aspirin can be appropriate for many people, it does have potential side effects. For example, aspirin can cause gastrointestinal bleeding, Reye syndrome in children and, in high doses, liver injury, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Talk to your healthcare provider before starting a regular aspirin regime.
December 30, 2015
Christopher Nystuen, MD, MBA