Design, synthesis and evaluation of a baicalin and berberine hybrid compound as therapeutic agent for ulcerative colitis

Structural modification of active natural compounds which were originated from Traditional Chinese Medicine (TCM) have showed great advantages in the development of new drugs. In TCM, “Huangqin - Huanglian” is a classic “medicine couple” that has been used to treat intestinal diseases for thousands of years, while baicalin and berberine are the major active compounds of Huangqin and Huanglian respectively. Based on this “medicine couple”, we designed and synthesized a new baicalin and berberine hybrid compound (BBH). Its molecular structure was confirmed by spectroscopy. The antibacterial activity of BBH was detected in vitro. Results indicated that the new hybrid compound exhibited the best antibacterial activity for proteobacteria as compared with its original synthetic materials (baicalin and berberine). In vivo, the effect of BBH on ulcerative colitis was also investigated. BBH treatment significantly ameliorated the disease symptoms and prevented the colon damage of ulcerative colitis. Furthermore, BBH showed a significant anti-inflammatory effect through regulating activities of SOD, MPO and expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in colon tissue. Data also suggested that BBH was more superior than baicalin and berberine in ameliorating colonic damage. This indicated that the new hybrid compound BBH showed enhanced efficacy in treating ulcerative colitis.