Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objective To investigate the effect and mechanism of Taxilli Herba decoction in preventing miscarriage in rats with threatened abortion.Methods Seventy-two SPF-grade SD rats were co-housed at a male-to-female ratio of 2∶1.Forty-eight pregnant rats were subsequently divided into a normal group,a threatened abortion model group,a positive control group,as well as Taxilli Herba decoction low/medium/high dose groups(n=8 rats per group).Rats in the positive control group received 3.02 mg/kg dydrogesterone intragastrically,and rats in the low-,medium-,and high-dose Taxilli Herba decoction groups received 2.5,5,and 10 g/kg Taxilli Herba decoction intragastrically,respectively.The normal and model groups received intragastric distilled water once a day for 10 consecutive days.On day 10 after administration of the corresponding treatment,rats in all groups except the normal group received intragastric administration of 3.75 mg/kg mifepristone suspension.The effects of Taxilli Herba on the vaginal bleeding rate and abortion rate were observed.Serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E),progesterone(P),vascular endothelial growth factor(VEGF),testosterone(T),and aromatase and E and P levels in the ovary in pregnant rats were detected by enzyme-linked immunosorbent assay.Expression levels of E receptor(ER),P receptor(PR),VEGF receptor 2(VEGFR2),and platelet endothelial cell adhesion molecule-1(CD31)in the uterine decidua in pregnant rats were detected by immunofluorescence staining,and semi-quantitative analysis was performed.Results Mifepristone significantly increased the vaginal bleeding rate and abortion rate in pregnant rats,but these were effectively reduced by treatment with Taxilli Herba water decoction.Taxilli Herba water decoction also increased serum E,P,and VEGF,and ovary levels of E and P(P＜0.05).The treatment also decreased serum LH,maintained the secretion of FSH,and enhanced ER,PR,VEGFR2,and CD31 expression in decidual tissue.Conclusions Taxilli Herba demonstrated effective miscarriage-prevention effects in a rat model of threatened abortion.Its mechanism of action involves regulating the normal physiological function of the hypothalamic-pituitary-gonadal axis upstream of the uterus,and enhancing the expression of the downstream P/PR/VEGF/VEGFR2 and E/ER/VEGF/VEGFR2 pathways.

Objective To investigate the effect and mechanism of Taxilli Herba decoction in preventing miscarriage in rats with threatened abortion.Methods Seventy-two SPF-grade SD rats were co-housed at a male-to-female ratio of 2∶1.Forty-eight pregnant rats were subsequently divided into a normal group,a threatened abortion model group,a positive control group,as well as Taxilli Herba decoction low/medium/high dose groups(n=8 rats per group).Rats in the positive control group received 3.02 mg/kg dydrogesterone intragastrically,and rats in the low-,medium-,and high-dose Taxilli Herba decoction groups received 2.5,5,and 10 g/kg Taxilli Herba decoction intragastrically,respectively.The normal and model groups received intragastric distilled water once a day for 10 consecutive days.On day 10 after administration of the corresponding treatment,rats in all groups except the normal group received intragastric administration of 3.75 mg/kg mifepristone suspension.The effects of Taxilli Herba on the vaginal bleeding rate and abortion rate were observed.Serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen(E),progesterone(P),vascular endothelial growth factor(VEGF),testosterone(T),and aromatase and E and P levels in the ovary in pregnant rats were detected by enzyme-linked immunosorbent assay.Expression levels of E receptor(ER),P receptor(PR),VEGF receptor 2(VEGFR2),and platelet endothelial cell adhesion molecule-1(CD31)in the uterine decidua in pregnant rats were detected by immunofluorescence staining,and semi-quantitative analysis was performed.Results Mifepristone significantly increased the vaginal bleeding rate and abortion rate in pregnant rats,but these were effectively reduced by treatment with Taxilli Herba water decoction.Taxilli Herba water decoction also increased serum E,P,and VEGF,and ovary levels of E and P(P＜0.05).The treatment also decreased serum LH,maintained the secretion of FSH,and enhanced ER,PR,VEGFR2,and CD31 expression in decidual tissue.Conclusions Taxilli Herba demonstrated effective miscarriage-prevention effects in a rat model of threatened abortion.Its mechanism of action involves regulating the normal physiological function of the hypothalamic-pituitary-gonadal axis upstream of the uterus,and enhancing the expression of the downstream P/PR/VEGF/VEGFR2 and E/ER/VEGF/VEGFR2 pathways.