No abstract

With the increasing incidence of ulcerative colitis (UC) in China, Chinese medicinal herbs or relatively active compounds are widely applied in treating UC. These medicines may be combined with other therapeutic agents such as vitamin D3. Nevertheless, the efficacy of these combinations for UC is unclear. Geniposide is an active component in many Chinese herbal medicines. It could ameliorate dextran sulfate sodium (DSS)–induced colitis in mice. This study was designed to determine the efficacy and mechanism of the single use and combination of geniposide and vitamin D3 on a mouse model of acute colitis. Data showed that a single administration of geniposide (2 mg/kg) or vitamin D3 (4 IU/day) could significantly improve the symptoms of UC and relieve colon damage. Geniposide and vitamin D could significantly decrease the levels of TNF-α and IL-6 in serum and colon, and increase the level of IL-10 in the colon. However, the combined treatment of geniposide (2 mg/kg) and vitamin D3 (4 IU/day) exerted less beneficial effects on UC in mice, indicating by less improvement of UC symptoms, colon damage, and inflammatory infiltration. The combination only downregulated the level of TNF-α in serum and IL-6 in the colon. Our data further demonstrated that geniposide could inhibit the activation of p38 MAPK and then restrict the vitamin D receptor signaling stimulated by vitamin D3. These results implied that the combination of geniposide and vitamin D3 might not be an ideal combined treatment for acute colitis, and the combination of vitamin D supplementary and geniposide (or herbal medicines rich in geniposide) need more evaluation before being applied to treat UC in clinic.

Due to the complexity and diverse causes, the pathological mechanism of diet-induced colonic injury and colitis remains unclear. In this study, we studied the effects of the combination of a high-fat diet (HFD) plus alcohol on colonic injury in mice. We found HFD plus alcohol treatment induced disturbance of the gut microbiota; increased the production of intestinal toxins lipopolysaccharide (LPS), indole, and skatole; destroyed the stability of the intestinal mucosa; and caused the colonic epithelial cells damage through the activation of nuclear factor (NF)-κB and aromatic hydrocarbon receptors (AhR) signaling pathways. To mimic the effect of HFD plus alcohol in vivo, NCM460 cells were stimulated with alcohol and oleic acid with/without intestinal toxins (LPS, indole, and skatole) in vitro. Combinative treatment of alcohol and oleic acid caused moderate damage on NCM460 cells, while combination with intestinal toxins induced serious cell apoptosis. Western blot data indicated that the activation of NF-κB and AhR pathways further augmented after intestinal toxins treatment in alcohol- and oleic acid-treated colonic cells. This study provided new evidence for the relationship between diet pattern and colonic inflammation, which might partly reveal the pathological development of diet-induced colon disease and the involvement of intestinal toxins.