Researchers from University of Glasgow, Scotland, have identified that a compound naturally found in grapefruit, orange and tomatos can eventually be used in therapies for chronic inflammation, a pathological hyperactivity of the immune system which can cause heart diseases, diabetis and even cancer. The results were published in the Biochemical Journal and can lead to the production of new anti-inflammatory drugs.
The sleepless guardian, the immune system, protects us from anything foreign that enters our body. When a germ or virus enters your blood stream, when you injure your skin, the immune system responds immediately to fight and fix the damage. This is the acute immune response producing pro-inflammatory substances and later is turned off when there danger vanishes. However, if the immune response remains active, it can cause chronic inflammation which will eventually cause damage in healthy areas in our bodies. Chronic inflammation, like a slow-burning fire, will deteriorate the inner lining of blood vessels (and cause atherosclerosis) or the joints (and cause arthritis). Chronic inflammation is also associated with cancer and several other pathological conditions.
Scientists are studying what happens at the molecular level during chronic inflammation. For example, previous studies have shown that STAT3, a multifunctional enzyme, is hyper active in chronic inflammation and cancer when pro-inflammatory compounds, such as interleukin-6 (IL-6), are constantly produced in the blood. What is also known is that SOCS3, a transcription factor (a protein which regulates the expression of genes to proteins), keeps STAT3 on a short leash in normal conditions.
Dr Stephen Yarwood, Senior Lecturer in the Institute of Molecular Cell and Systems Biology, University of Glasgow, and his colleagues searched for a drug to produce more SOCS3 in the heart cells, which would eventually decrease STAT3 activity and inflammation.
They tested more than 1,000 compounds, approved by FDA, whether they can activate the SOCS3 gene. One compound among them, naringenin, caused a noticeable increase in SOCS3. Naringenin is a known free radical antioxidant found in grapefruits, oranges as well as the skin of tomatos. Naringenin is a type of flavonoid with anti-inflammatory function, immune system modulation and has anti-cancer and anti-viral properties. But since details on its molecular function are scarce, the researchers set out to elucidate naringenin’s function in human cells using as a model vascular endothelial cells (HUVEC).
So what does it do in the cell? Since previous studies have shown the cytotoxic levels of this compound, Jolanta Wiejak and Julia Dunlop, researchers in the Yarwood group, added a concentration of naringenin which is not toxic to the cells. They found that SOCS3 is increased concomitant to STAT3 activity being blocked. So, naringenin, has a double role by activating protective genes and protected the heart cells from chronic inflammation.
The authors will now look for protein targets of this compound in heart cells and will investigate their use as drug targets in therapies against chronic inflammatory diseases.