Plant extract may be effective against inflammatory bowel disease

The ongoing study by associate professor Moul Dey in SDSU's Department of Health and Nutritional Sciences -- funded by the National Institutes of Health -- moves on now to examine the potential use of the plant extract against colon cancer.

"There is an established link between ulcerative colitis and colon cancer. People who have ulcerative colitis are at significantly higher risk to have colon cancer," Dey said. "Whether this plant extract might help with colon cancer symptoms directly or perhaps delay the onset of colon cancer in ulcerative colitis patients, we don't know the answers to those questions, but it is something we would like to look into."

Dey and her team will carry out that research over the next two and a half years as she continues her work on a Pathway to Independence award for promising young scientists. That National Institutes of Health grant of nearly $900,000 over five years was awarded to Dey for work she began as a researcher at Rutgers University.

As a researcher at Rutgers starting in 2004, Dey developed a mammalian cell-based screening platform and screened nearly 3,000 plant extracts for potential anti-inflammatory activity. A plant-derived compound called Phenethylisothiocyanate, or PEITC, was one among others that showed potential anti-inflammatory activities. The NIH funded Dey's proposal to study it further.

PEITC is found in the Brassica genus of plants, which includes cabbage, cauliflower, watercress and broccoli. Barbarea verna, also known as upland cress or early wintercress, a herb that is used in salads, soups, and garnishes, is one of the richest sources of dietary PEITC in Dey's study.

Scientists had already studied the compound for its anticarcinogenic properties prior to Dey's investigation on its anti-inflammatory activities.

"I tested this substance in a mouse model that is already established and widely used. What we found is that it not only alleviates several clinical signs of ulcerative colitis -- for example, it attenuates the damage that occurs in the colon tissues and colon epithelium, as well as the clinical signs like diarrhea and blood in stool. The weight loss is a major sign in colitis and that was alleviated, too." However, she noted that although mammalian animal models are routinely used for an initial test of biological effects of compounds targeted for potential human use, obtained results may not always repeat in humans.

Inflammatory bowel disease, or IBD, is a set of chronic and relapsing inflammatory disorders of the intestine that affects an estimated 2 million people annually in the United States. Two common forms of IBD are Crohn's disease and ulcerative colitis.

When Dey and her colleagues looked into the mechanism by which the compound might be working against IBD, they found that it downregulates many of the genes that are known to be upregulated in human patients with colitis. That means the compound acts on cells to decrease the quantity of cellular components such as specific proteins that are produced abundantly in colitis patients. One such protein is a novel transcription factor. Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA.

"We are excited about these findings and our next step would be to see how this plant and the compounds from this plant may be effective against colon cancer, alleviating colon cancer or preventing the onset of colon cancer," Dey said.

"I am not a cancer biologist per se. My interests are really in cellular mechanisms of inflammatory diseases. The only reason we are going to study colon cancer in this particular project is because ulcerative colitis is very closely linked to colon cancer."

Colon carcinogenesis is highly preventable, yet colon cancer has one of the highest death rates among all cancers due to typical late diagnosis.

Since people already eat vegetables containing PEITC, there is a long history of human consumption with no adverse effects.

"Obviously the dose we are testing is significantly higher than what we eat in a vegetable, but we have done multiple safety tests and found that this dose is safe in animals," Dey said.

Dey has no plans to test the extract in humans as part of the current project, but said additional tests would be required if the extract leads to new drugs or treatments in humans.

Dey's co-authors are Peter Kuhn of Phytomedics Inc., of Jamesburg, N.J.; David Ribnicky, Kenneth Reuhl and Ilya Raskin of Rutgers University, and VummidiGiridhar Premkumar, who is currently at University of Cincinnati.