Original Article An old herbal medicine with a potentially new therapeutic application in inflammatory bowel disease

Inflammatory Bowel Disease (IBD) is a chronic and frequently disabling inflammatory disorder of the intes- tine. New developments in IBD therapy are primarily focused on biologic treatments; however, they are both expen- sive and associated with significant side effects. Here, we provide the first preclinical evidence that YunNan BaiYao (YNBY), a well-known traditional Chinese herbal remedy frequently used for treating hemorrhages and wounds, can effectively alleviate experimental colitis. Oral administration of YNBY in drinking water significantly reduced the dis- ease activities of both DSS- and TNBS-induced experimental colitis. Mechanistic studies revealed that the effective- ness of YNBY was not due to an anti-bacterial function since YNBY had no effect on E. coli growth. Rather, it exhibited an anti-inflammatory or immunosuppressive function: In the DSS colitis model, YNBY treatment decreased the levels of several pro-inflammatory cytokines in colonic mucosa, including TNFα, IL-12p40, and IL-17. Similar cytokine changes were also observed in mouse serum, suggesting that systemic changes in general reflect the changes in the affected colon. Significant down-regulation of IL-12p40 and IL-17, in addition to IFNγ, was also seen in TNBS-colitis model. Another potential mechanism for the anti-inflammatory effects of YNBY involves the selective suppression of pro-inflammatory immune cells: YNBY effectively suppressed the growth of multiple T- and B-lymphocytes, including Molt-4, Jurkat, and EBV-transformed human B-lymphocytes, more potently than 6-mecaptopurine (6-MP) and 5- aminosalicylic acid (5-ASA), two of the most commonly used first-line drugs in IBD therapy. In sharp contrast, YNBY exhibited no cytotoxicity to colonic epithelial cells (Caco-2 cells), even at the concentration 10-fold higher than that used in the lymphocyte model; and instead promoted cell spreading and wound healing. These results strongly sug- gest that YNBY not only has effective anti-inflammatory properties through suppressing lymphocyte growth and pro- inflammatory cytokine expression, but also can promote intestinal epithelial wound-healing and repair. Therefore, YNBY demonstrates strong potential as an alternative herbal therapy for IBD.