eNews August 24, 2010

Herbal medicine alleviates inflammatory bowel disease (IBD) in mice

Inflammatory bowel disease (IBD) is a complex heterogeneous group of gastrointestinal diseases that affects some 2,000,000 Americans yearly (Dey et al. 2010). Its two most common forms are Crohn's disease and ulcerative colitis. It is likely due to a complex interaction of genetic and environmental factors that prevent the immune system from suppressing inflammatory responses to normal enteric flora (Farmer et al. 2001). The drugs currently used to treat IBD are few, not very effective and can have negative side effects. The development of new therapies, including plant derivatives, is being actively pursued. A research team led by Dr. Ilya Raskin of Rutgers University, Biotechnology Center, New Brunswick, NJ, has found that a naturally occurring compound in cole crops may be particularly effective in treating ulcerative colitis (Dey et al. 2010).

DSS-induced IBD

Among the more common animal models of IBD is the dextran sodium sulfate (DSS)-induced model. It can be modified to simulate either acute or chronic colitis and presents some important human IBD phenotypes. The acute model requires a higher DSS concentration and a shorter induction time; in addition, it produces earlier and more severe symptoms. The chronic model produces later but longer-lasting symptoms that may flare-up and remit in cycles.

An herbal compound outperforms a conventional IBD treatment

JAX® Mice strain C57BL/6J can be used in the DSS-induced model of IBD.

One of the promising plant-derived IBD therapies might involve the use of phenethylisothiocyanate (PEITC), a well-studied substance belonging to a group of naturally occurring sulfur-containing compounds called isothiocyanates, commonly found in cole crop family (Brassicaceae) vegetables, such as cabbage, cauliflower, watercress and broccoli. One of the richest sources of PEITC is the seeds from land cress (Barbarea verna), an herb used in salads, soups and garnishes. Although PEITC has been shown to have anti-cancer, anti-oxidant, and anti-inflammatory properties, its therapeutic effects in IBD were unknown.

Dr. Raskin and his colleagues compared the efficacy of PEITC essential oil (PEO), which is more than 95% natural PEITC, and mesalamine, a standard therapy for mild-to-moderate ulcerative colitis, to mitigate DSS-induced acute and chronic IBD in C57BL/6J mice (B6J, 000664). They found that, in virtually all instances, PEO outperforms (often significantly) mesalamine in remitting acute and chronic DSS-induced ulcerative colitis. PEO-treated mice weigh more, have a healthier colon and bowel, have better stool consistency, exhibit less infiltration of inflammatory cells and produce less of the inflammatory cytokine IL1B in the colon than either diseased mice or mesalamine-treated mice. In the acute model, PEO-treated mice are almost as healthy as normal B6J mice. In the chronic model, PEO-treated mice fare significantly better and continue to improve during the treatment course, but mesalamine-treated mice do not show any significant remission.

PEO suppresses key inflammatory cytokines

Dr. Raskin's team also compared the expression patterns of immune function-related genes, transcription factors, and cytokines in PEO-treated and diseased mice. They found that PEO affects an intricate network of immune-signaling genes. Twenty-one of 84 genes activated by lipopolysaccharide (LPS – an agonist of toll-like receptor 4 signaling, which plays a critical role in colitis) are suppressed three-fold or more by PEO. These 21 genes are key transcription factors and inflammatory mediators. Seven of the 21 genes, including IL6, had not been known to be affected by PEO. Changes in the expression levels of three of these seven genes (Il6, Cxcl10, and Stat1) depend on PEO concentrations, and all three are activated in human ulcerative colitis.

The findings by Dr. Raskin and his colleagues indicated that PEO likely mitigates ulcerative colitis by suppressing STAT1 transcription and inhibiting proinflammatory cytokines. Importantly, they suggest that PEO might be a promising therapy for ulcerative colitis.

References

Dey M, Kuhn P, Ribnicky D, Premkumar VG, Reuhl K, Raskin I. 2010. Dietary lephenethylisothiocyanate attenuates bowel inflammation in mice. BMC Chemical Biology 10:4-16.

Farmer MA, Sundberg JP, Bristol IJ, Churchill GA, Li R, Elson CO, Leiter EH. 2001. A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice. Proc Natl Acad Sci U S A 98:13820-5.