Objective To study the effects of ethanol extract of the root of anacyclus pyrethrum(EEAP)on blood glucose and gut microbiota in mice induced by high-fat diet.Methods Forty-eight male C57BL/6N mice were randomly allocated into groups using a random number table:control group,model group,low-,medium-,and high-dose EEAP groups,as well as a metformin group,with each group consisting of 8mice.Mice in the low,medium,and high dose EEAP groups were administered EEAP at 100,200 and 400mg/kg,respectively.The metformin group was given metformin at 280mg/kg.Both the control and model groups were given an equivalent a-mount of distilled water.Gavage was performed once daily for 12 consecutive weeks.Except the control group mice were fed normal diet,the other groups were fed high-fat diet.Fasting and random blood glucose were detected by blood glucose test strips.The levels of in-flammatory factors in mice were detected by enzyme-linked immunosorbent assay kit.Gut microbiota was detected by 16S rDNA real-time quantitative polymerase chain reaction.Results At 12th weeks,compared with the model group,the body mass of mice in low-dose,medium-dose and high-dose EEAP groups and metformin group were decreased significantly.Compared with the model group,the fasting blood glucose and random blood glucose in high-dose EEAP group and metformin group were significantly decreased.Com-pared with the model group,the abundations of Akkermansia muciniphila and Faecalibacterium prausnitzii in the intestinal tracts of mice in medium-dose and high-dose EEAP groups and metformin group were significantly increased,while the abundations of desulfovibrio were significantly decreased.Conclusion EEAP can improve dysglycemia induced by high-fat diet in mice,and its mechanism may be related to regulating gut microbiota and inhibiting inflammatory reaction.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

Objective To study the effects of ethanol extract of the root of anacyclus pyrethrum(EEAP)on blood glucose and gut microbiota in mice induced by high-fat diet.Methods Forty-eight male C57BL/6N mice were randomly allocated into groups using a random number table:control group,model group,low-,medium-,and high-dose EEAP groups,as well as a metformin group,with each group consisting of 8mice.Mice in the low,medium,and high dose EEAP groups were administered EEAP at 100,200 and 400mg/kg,respectively.The metformin group was given metformin at 280mg/kg.Both the control and model groups were given an equivalent a-mount of distilled water.Gavage was performed once daily for 12 consecutive weeks.Except the control group mice were fed normal diet,the other groups were fed high-fat diet.Fasting and random blood glucose were detected by blood glucose test strips.The levels of in-flammatory factors in mice were detected by enzyme-linked immunosorbent assay kit.Gut microbiota was detected by 16S rDNA real-time quantitative polymerase chain reaction.Results At 12th weeks,compared with the model group,the body mass of mice in low-dose,medium-dose and high-dose EEAP groups and metformin group were decreased significantly.Compared with the model group,the fasting blood glucose and random blood glucose in high-dose EEAP group and metformin group were significantly decreased.Com-pared with the model group,the abundations of Akkermansia muciniphila and Faecalibacterium prausnitzii in the intestinal tracts of mice in medium-dose and high-dose EEAP groups and metformin group were significantly increased,while the abundations of desulfovibrio were significantly decreased.Conclusion EEAP can improve dysglycemia induced by high-fat diet in mice,and its mechanism may be related to regulating gut microbiota and inhibiting inflammatory reaction.

ObjectiveTo preliminarily predict the targets and signaling pathways of indole-3-methanol in the treatment of obesity based on molecular docking technology and network pharmacology， and then verify the prediction results by the experiment in vitro. MethodThe pharmacological targets of indole-3-methanol were obtained from SwissTargetPrediction and literature review. Obesity-related targets were obtained from Online Mendelian Inheritance in Man （OMIM）， GeneCards， and Comparative Toxicogenomics Database （CTD）. The protein-protein interaction network of the targets of indole-3-methanol and obesity was built by STRING. Cytoscape 3.8.2 was used for target screening. Gene ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the common targets shared by obesity and indole-3-methanol in DAVID 6.8. AutoDock Vina 1.1.2 was employed to perform the molecular docking between indole-3-methanol and disease targets. Finally， the in vitro experiment was carried out to verify the anti-obesity effect of indole-3-methanol. ResultIndole-3-methanol and obesity shared 80 common targets， which included matrix metalloproteinase （MMP）-9， Janus kinase （JAK） 2， etc. KEGG enrichment predicted that indole-3-methanol mainly acted on tumor necrosis factor （TNF）， vascular endothelial growth factor （VEGF）， tyrosine kinase receptor 2 （ErbB2）， and epidermal growth factor receptor （EGFR） signaling pathways in the treatment of obesity. Molecular docking showed that indole-3-methanol had good binding activity with fat mass and obesity-associated protein （FTO）. The results of Western blot， MTT assay， and oil-red O staining showed that indole-3-methanol down-regulated the expression of FTO in 3T3-L1 cells （P<0.05）. ConclusionIndole-3-methanol may treat obesity by down-regulating the expression of FTO protein and further inhibiting adipocyte proliferation. This study provides an experimental basis for deciphering the anti-obesity mechanism of indole-3-methanol.