The Effect And Mechanism Of Baweixileisan And Alpha Linolenic Acid For Inflammatory Bowel Disease

Genetically based interactions between the human intestinal microbiome and the mucosal immune system and the manner by which environmental factors modify these relationships appear particularly relevant in the development of inflammatory bowel disease(IBD).The incidence of this disease in Asia is rapidly increasing,which may link to increased contact with the West countries,especially westernization of diet.Over the last few years,the complementary and alternative medicine(CAM),such as traditional Chinese medicine and omega-3 polyunsaturated fatty acids(n3-PUFA),has attracted more and more attention among IBD patients.However,their effectiveness is inconsistent,at the same time,the precise mechanisms behind its anti-inflammatory effects remain largely unknownBawei Xileisan(BXS)is a traditional Chinese medicine formula,which has been used for many years to clinically treat conditions associated with ulcerative colitis.However,the underlying mechanism of BXS is covered.The study was undertaken to evaluate the therapeutic effect of BXS on dextran sulfate sodium(DSS)-induced mouse colitis model and further to elucidated the possible underlying molecular mechanisms.Experimental colitis was induced in female C57BL/6 mice by dissolving 3%DSS in their drinking water for 5 days.BXS treatment(200 or 400 mg/kg)was administered daily through rectally administered for 7 days.Body weight,colon length,histological changes,serum Th17 cytokine levels,Th17 and Treg in Splenocytes mononuclear cells(SPMNC),as well as the absolute number of Bacteroides and Lactobacillus in feces were all measured after treatment.BXS administration(200 or 400 mg/kg)profoundly ameliorated DSS induced clinical manifestations,body weight loss,colon shortening and histological damage.In addition,BXS also significantly and dose-dependently reduced the expression of Th17-related cytokines IL-17A,IL-17F,and IL-22,along with the restored Th17/Treg balance.Moreover,the treatment can also improve the Lactobacillus levels and demonstrated beneficial effects on Bacteroides.Taken together,our findings suggest that the major mechanism of BXS efficacy is associated with the intervention of Th17 pathway and Th17/Treg imbalance,on the other hand,by partially change the gut microbiota.Aipha linolenic acid(ALA),one of the n3-PUFA,is synthesized by plants.Mammals do not possess the enzyme △-15 desaturase,thus they have to obtain this fatty acid from the diet.The study was undertaken to evaluate the relationship between high fat high sugar diet(HFHSD)and IBD,the therapeutic effect of alpha linolenic acid(ALA)on trinitrobenzene sulfonic acid(TNBS)-induced mouse colitis model and further to elucidated the possible underlying molecular mechanisms.Female BABL/c mice were fed normal diet(ND)or high fat high sugar diet(HFHSD)for 9 weeks.At the same time,ALA treatment(150 or 200 mg/kg)was administered daily for 9 weeks.Experimental colitis was induced by the intracolonic administration of TNBS(1mg in 50%ethanol)to mice in day 0.Mice were euthanized in day 3.Body weight,spleen weight,colon length,disease activity index(DAI),histological changes,T cell related cytokine levels,as well as lipid distribution were all measured after treatment.HFHSD induced severe colitis induced clinical manifestations,colon shortening and histological damage.ALA(150 mg/kg)administration profoundly ameliorated TNBS-induced clinical manifestations,body weight loss,spleen weight loss,colon shortening and histological damage.On the contrary,ALA(300 mg/kg)administration did not ameliorate colitis,or even exacerbated disease.HFHSD consumption was associated with assisting TNBS in changing IL-12,IFN-γ,IL-2 and IL-17A lever.As expectation these changes were recovered by ALA(150 mg/kg).At the same time,HFHSD had a significant impact on total cholesterol(TC),triglyceride(TG)and high density lipoprotein cholesterol(HDL-C).In conclusion,HFHSD contributed to exacerbate TNBS-induced colitis via Th1/Th17 pathway.ALA(150 mg/kg)showed ALA(150 mg/kg)showed protective effects against TNBS-induced colitis via Thl/Th2/Th17 pathway.What is more these results support the need to establish a tolerable upper limit for ALA intake particularly in the context of chronic inflammatory conditions such as IBD.