Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance

BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper(mTh)cells and memory follicular T helper(mTfh)cells is a potential therapeutic strategy against ulcerative colitis(UC).Because of its anti-inflammatory and immunomodulatory properties,curcumin(Cur)is a promising drug for UC treatment.However,fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.AIM To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium(DSS)in mice by regulating the mTh and mTfh immune homeostasis.METHODS Balb/c mice were administered 3%and 2%DSS to establish the UC model and treated with Cur(200 mg/kg/d)by gavage on days 11-17.On the 18th d,all mice were anesthetized and euthanized,and the colonic length,colonic weight,and colonic weight index were evaluated.Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining.Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry.Western blotting was performed to detect SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in colon tissues.RESULTS Cur effectively mitigates DSS-induced colitis,facilitates the restoration of mouse weight and colonic length,and diminishes the colonic weight and colonic weight index.Simultaneously,it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane.While the percentage of Th1,mTh1,Th7,mTh7,Th17,mTh17,Tfh1,mTfh1,Tfh7,mTfh7,Tfh17,and mTfh17 cells decreased after Cur treatment of the mice for 7 d,and the frequency of mTh10,Th10,mTfh10,and Tfh10 cells in the mouse spleen increased.Further studies revealed that Cur administration prominently decreased the SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in the colon tissue.CONCLUSION Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage,potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling

BACKGROUND Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease(IBD),which is mainly related to lymphocytes(T or B cells,including memory B cells),mast cells,activated neutrophils,and macrophages.As the precursor of B cells,the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells,whose dysfunction can easily lead to autoimmune diseases,including IBD.AIM To investigate whether or not curcumin(Cur)can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.METHODS Colitis was induced in mice with a dextran sulphate sodium(DSS)solution in drinking water.Colitis mice were given Cur(100 mg/kg/d)orally for 14 consecutive days.The colonic weight,colonic length,intestinal weight index,occult blood scores,and histological scores of mice were examined to evaluate the curative effect.The levels of memory B cells in peripheral blood of mice were measured by flow cytometry,and IL-1β,IL-6,IL-10,IL-7A,and TNF-αexpression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay.Western blot was used to measure the expression of Bcl-6,BLNK,Syk,and other signaling pathway related proteins.RESULTS After Cur treatment for 14 d,the body weight,colonic weight,colonic length,colonic weight index,and colonic pathological injury of mice with colitis were ameliorated.The secretion of IL-1β,IL-6,TNF-α,and IL-7A was statistically decreased,while the IL-35 and IL-10 levels were considerably increased.Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM,IgG,IgA,FCRL5,CD103,FasL,PD-1,CD38,and CXCR3 on the surface of CD19^(+)CD27^(+)B cells,while the number of CD19^(+)CD27^(+)IL-10^(+)and CD19^(+)CD27^(+)Tim-3^(+)B cells increased significantly.In addition,Cur significantly inhibited the protein levels of Syk,p-Syk,Bcl-6,and CIN85,and increased BLNK and p-BLNK expression in colitis mice.CONCLUSION Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism

BACKGROUND Studies have shown that a high-fat diet(HFD) can alter gut microbiota(GM)homeostasis and participate in lipid metabolism disorders associated with obesity.Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract(Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases.AIM To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism.METHODS Obesity was induced in rats with an HFD for 7 wk, and Sal(0.675 g/1.35 g/2.70g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors(cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNAbased microbiota analysis and untargeted lipidomic analysis(LC-MS/MS),respectively.RESULTS Sal treatment markedly reduced weight, body fat index, serum triglycerides(TG), total cholesterol(TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein(HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as c AMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs(TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs(DG14:0/22:6, DG22:6/22:6), CL(18:2/18:1/18:1/20:0), and increased ceramides(Cers;Cer d16:0/21:0, Cer d16:1/24:1),(O-acyl)-ω-hydroxy fatty acids(OAHFAs;OAHFA18:0/14:0) in the feces of rats. Spearman’s correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite.CONCLUSION Sal has an anti-obesity effect by regulating the GM and lipid metabolism.