Weizmann Institute of Science researchers have found a way to trigger a natural defense mechanism to alleviate inflammatory diseases of the bowel.

A study in mice, published in Cell Reports and led by veterinarian Noa Stettner, a student in the lab of Ayelet Erez, focused on nitric oxide, a signaling molecule in many biological processes. Scientists have long wondered what role NO plays in such inflammatory conditions as Crohn’s disease and ulcerative colitis, with NO alleviating intestinal inflammation in some circumstances and promoting it in others.

The Weizmann researchers hypothesized that NO has different effects in different types of cells in the gut, so the team genetically engineered mice to block NO production exclusively in cells making up the inner lining of the gut or in immune cells.

Colitislike disease got worse when NO synthesis was blocked in the gut cells but improved when NO was blocked in the immune cells.

The next step was to find a way to increase the production of NO in mice only in the lining of the gut.

Using Erez’s earlier finding that an enzyme called ASL makes the raw material for NO, the researchers combined two natural ASL-boosting supplements: fisetin, present in apples, persimmons and strawberries, and citrulline, found in watermelon, beets and spinach.

Weizmann Institute graphic

When used together, the enzymes promoted NO manufacture only in the inner lining of the gut. The symptoms of the inflammatory disease then improved, and, in mice with colon cancer, the number and size of tumors decreased.

If this approach is shown to raise NO levels in the cells in the inner lining of the gut of humans, it could be a natural way to treat inflammatory bowel diseases and even colon cancer. The fact that it makes use of over-the-counter nutritional supplements should facilitate its implementation.