Main Active Component Of Pogostemon Cablin Or Coptis Chinensis Protects Against Dextran Sulfate Sodium-Induced Colitis In Mice: Effect And Mechanism Research

ObjectiveInflammatory bowel diseases (IBD) is a chronic and relapsing intestinal tract inflammatory disease, characterized by diarrhea, abdominal pain, and rectal bleeding due to aberrant intestinal inflammation. These bowel-inflammatory symptoms greatly decreased the quality of life. During the development procedure of IBD, the intestinal epithelial and mucosal immune system barrier is the first line of defense which can resist bacteria, virus and food antigen invades. So it is very important to maintain its integrity. Moreover, the imbalance of proinflammatory and anti-inflammatory factor cause the normal intestinal tissue unduly mucosal immune response which lead to intestinal mucosal damage. Therefore, it is of great significance to further understand the pathogenesis of IBD and seek effective drugs for the treatment of IBD via the anti-inflammatory and restoration of intestinal barrier.Pogostemon cablin (Blanco) Benth and Coptis chinensis were Chinese traditional Chinese medicines which have a long history for treatments of gastrointestinal disease including colitis. Previous studies shown that treatment with patchouli oil and pogostone, mian volatile components of Pogostemon cablin, and berberine, one of the major alkaloid compositions of Coptis, minimized the symptoms of IBD. Patchouli alcohol (PA) was selected as the index component used to evaluate the quality of patchouli medicinal materials. Moreover, palmatine (PMT) and berberubine (BB), which structure was similar to the berberine, were the alkaloid components in coptidis. Hence, we deduced that PA and alkaloid which including PMT and BB may have a potential therapeutic effect of IBD. In this study, the potential effect of them against IBD was investigated in the view of protective effect on intestinal mucous membrane barrier and regulation effect on the balance of inflammatory cytokines, for a better illumination of the etiology of TBD.MethodsBalb/C Mice with DSS (30 mg/mL, drink freely) induced colitis were oral treated with PA (10,20 and 40 mg/kg) or BB (10,20 mg/kg) or PMT (50,100 mg/kg) or BBR (50mg/kg, control drug for BB and PMT) or SASP (200 mg/kg, positive drug) once daily for 7 days. Disease activity index (DAI), the degree of colonic injuries (macroscopic colon length, and histopathology and microscopic colonic damage scores, colonic mucin mRNA expression) and colonic inflammation parameters [myeloperoxidase activity and inflammation factors (TNF-α, IL-1β, IL-6, IFN-y, IL-12, IL-17, IL-10, IL-4)] were analyzed. In addition, the expression of colonic tight junctions (Z0-1, ZO-2, occludin and claudin-1) and classical apoptosis related proteins (Bax and Bcl-2) were detected by western blot method in alkaloids (BB, PMT and BBR) group and the corresponding control (DSS and positive drug) group.ResultsThis research found that PA, BB, and PMT significantly reduced DAI, restored the colon length, repaired colonic pathology variation, decreased histological scores and down-regulated the MPO activity, as well as increased the expression of mucin-1 and mucin-2 mRNA in DSS-treated mice. In addition, the level of inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ, IL-10 and IL-4) in DSS group were remarkable inhibited after treated with PA (40 mg/kg),BB(20 mg/kg) or PMT(100 mg/kg). When compare with DSS-treated mice, the expression of colonic tight junctions (Z0-1, ZO-2, occludin and claudin-1), as well as the concentration of proteins Bcl-2 were up-regulated in group. Furthermore, the expression of Bax was observably down-regulated after treated with BB (20 mg/kg) or PMT (100 mg/kg).ConclusionPA, BB and PMT have therapeutic effect, which closely related to maintain intestinal barrier function and inhibit the inflammatory response, on DSS induced colitis. Evidences presented that PA increased colonic adhesion protein expression, while BB and PMT preserved the structural integrity of the tight junctions, as well as suppressed apoptosis, then repaired intestinal barrier function. Besides, they all alleviated intestinal inflammation by supressing the expression of inflammatory markers and the infiltration, of inflammatory cells. The effect of them appeared to be by maintaing the normal intestinal tissue structure, whether after promoting the intestinal digestion and absorption of nutrients and improving adverse symptoms such as abdominal pain, diarrhea, bloody.