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ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan （ZSS） on constipation-predominant irritable bowel syndrome （C-IBS） rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank， model， positive drug （pinaverium bromide， 15.625 mg·kg-1）， raw ZSS， stir-fried ZSS， bran-fried ZSS， charcoal-fried ZSS and finished ZSS groups （3.75 g·kg-1）， with 10 rats in each group. Except for the blank group， which received intragastric administration of 0.9% sodium chloride solution at room temperature， all other groups were administered the ice solution at 0 to 4 ℃ （2 mL·d-1， for a total of 14 d） to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， neuro-peptide Y （NPY）， calcitonin gene-related peptide （CGRP）， substance P （SP）， diamine oxidase （DAO） and D-lactic acid （D-LA） were detected by enzyme linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate （cAMP）， protein kinase A （PKA） and aquaporin-3 （AQP3） mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids （SCFAs） was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group， the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased （P<0.01）， and the levels of 5-HT， VIP， CGRP and SP in serum were significantly increased. Simultaneously， the NPY levels significantly decreased （P<0.01）， the levels of DAO and D-LA in plasma were significantly increased （P<0.01）， and the mucosal epithelium of colon tissue was slightly damaged， with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3， cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased （P<0.05， P<0.01）. The total amount of SCFAs in feces showed an obvious decreasing trend， with the contents of acetic acid， isobutyric acid， isovaleric acid， valeric acid and caproic acid decreased significantly， while the contents of propionic acid and butyric acid increased significantly （P<0.05， P<0.01）. Compared with the model group， the treatment groups increased the intestinal propulsion rate， improved the intestinal mucosal barrier function， and adjusted the level of serum brain-gut peptide in C-IBS rats （P<0.05， P<0.01）. The expression levels of AQP3， cAMP， PKA mRNA and VIP， AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces， and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.
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OBJECTIVE To investigate the effects of Cistanches Herba polysaccharides （abbreviated as CDPS） on rats with constipation-predominant irritable bowel syndrome （IBS-C）. METHODS SD rats were divided into control group （20 rats） and modeling group. The modeling group was given 2 mL of normal saline at 0-4 ℃ intragastrically （once a day， for 14 consecutive days） to induce IBS-C model. After modeling， model rats were grouped into model group， positive control group （mosapride citrate， 1.35 mg/kg）， CDPS low-dose group （50 mg/kg） and CDPS high-dose group （100 mg/kg）， with 20 rats in each group. Administration groups were given corresponding drug solution intragastrically， and control group and model group were given a constant volume of water intragastrically， once a day， for 28 consecutive days. The fecal water content， serum content of 5-hydroxytryptamine （5-HT）， and charcoal powder propulsion rate of rats were determined in each group；the pathological morphology of colon tissue was observed， and mRNA and protein expressions of nerve growth factor （NGF） and tropomyosin receptor kinase A （TrkA） in colon tissue were detected. RESULTS Compared with control group， the fecal water content and carbon powder propulsion rate in the model group were decreased significantly （P＜0.05）； the rupture of mucosal muscle layer in colon tissue， significant infiltration of inflammatory cells and cellular edema were observed； the content of 5-HT in serum， and relative mRNA and protein expressions of NGF and TrkA were increased significantly （P＜0.05）. Compared with model group， the fecal water content and carbon powder propulsion rate of rats were increased significantly in administration groups （P＜0.05）， and pathological changes of colon tissue were relieved significantly， while the content of 5-HT in serum， the mRNA and protein expressions of NGF and TrkA in colon tissue were decreased significantly （P＜0.05）； among them， the above indicators inthe positive control group and CDPS high-dose group were generally close to those in the control group （P＞0.05）. CONCLUSIONS CDPS can alleviate the symptoms of IBS-C rats， which may be related to the inhibition of NGF/TrkA signaling pathway.
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Objective:To explore the potential mechanism of Bianketong tablet （BKT） in the treatment of constipation-predominant irritable bowel syndrome （C-IBS） based on network pharmacology and bioinformatics. Method:The BKT-meridian network was constructed for analyzing the combined effect of the nine Chinese herbs in BKT. The active components and targets of BKT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and then screened according to the oral bioavailability （OB） and drug likeness （DL） criteria. Following the acquisition of C-IBS target set from GeneCards， Online Mendelian Inheritance in Man （OMIM）， Drugbank and DisGeNet， the protein-protein interaction （PPI） network was constructed. Cytoscape 3.7.2 was utilized for network visualization. The screened key targets were subjected to gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID platform. The C-IBS mouse model was established via intragastric administration of ice water， and the key targets of BKT against C-IBS were verified by enzyme linked immunosorbent assay （ELISA） and immunohistochemistry. Result:The large intestinal meridian was the main site where BKT acted. There were 70 potential active components in BKT， which acted on 227 intersection targets. Through T helper cell 17（Th17） differentiation， Toll-like receptor （TLR）， tumor necrosis factor and other signaling pathways， BKT participated in inflammatory response， immune regulation， intestinal nerve regulation， hormonal regulation， and oxidative stress response， thus exerting the therapeutic effects against C-IBS. As reveled by <italic>in vivo</italic> experiments， BKT significantly improved the small intestinal propulsion rate， up-regulated the expression of vasoactive intestinal peptide （VIP） in serum and colon tissue of C-IBS mice， and down-regulated the expression of nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， interleukin（IL）-6， and TLR2 in serum and colon tissue， which confirmed the reliability of integration analysis. Conclusion:BKT inhibits C-IBS via multiple components， multiple targets， and multiple pathways. This study has provided ideas for further clinical research and experimental verification of BKT in the treatment of C-IBS.
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Objective To compare the differences of lifestyle factors between patients with functional constipation (FC)and constipation-predominant irritable bowel syndrome (IBS-C).Methods From February 2011 to December 2014,255 patients with chronic constipation were enrolled.Among them,there were 170 FC patients and 85 IBS-C patients.At the same period,170 healthy volunteers without symptoms of digestive diseases within one year were recruited as control.The data of demographic information and lifestyle factors were collected.First,single variant analysis was performed for statistical analysis and then the statistically significant variants were analyzed by multivariate logistic regression. Then the factors of FC and IBS-C patients were analyzed by decision tree model and the effects of factors under different categories were analyzed.Results The results of single variant analysis indicated that there was no difference in lifestyle factors between FC group and IBS-C group (all P >0.05).The results of multivariate logistic regression analysis showed that no independent protective or risk factors were found in IBS-C group compared with FC group.According to decision tree model analysis,body mass index (BMI),water intake per day and constipation family history were finally enrolled.The incidence of FC was higher in patients with BMI (66.67%).The incidence of FC was highest in patients with BMI≥23.56 kg/m2 and family history of constipation (70.00%).The total prediction accuracy of this model was 64.6% (42/65 )and area under curve (AUC)value was 0.688.Conclusions FC and IBS-C are related with many lifestyle factors.Low BMI and less water intake per day are influence factors of FC,while higher BMI and family history of constipation are influence factors of IBS-C.
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Objective To investigate the clinical effects of biofeedback therapy on constipation-predominant irritable bowel syndrome(IBS-C).Methods 30 patients with IBS-C were given to biofeedback therapy,5 times every treatment course.and then their clinical symptoms,mental state and quality of life before the treatment and at the end of treatment with biofeedback therapy were respectively evaluated by symptom scores,self-rating anxiety scale (SAS),self-rating depression scale (SDS),and short form 36 health survey questionnaire (SF-36).Results Post-treatment with biofeedback therapy,there were very significant decrease in total and subscales scores of bowel symptom including abdominal pain/discomfort,abdominal distension,abnormal appearance of defecation,abnormal process of defecation((12.31±2.01) vs (19.16±2.17),(2.95±0.57) vs (5.04±1.04),(2.64±0.92) vs (4.25±1.09),(3.66±1.09) vs (5.10±0.57),(3.06±1.08) vs (4.77±0.95) respectively,P＜0.01).The integration of SAS and SDS were obviously decreased after treatment((39.53±6.39) vs (44.43±7.89),P＜0.05;(40.70±8.38) vs (46.46±8.74),P＜0.05),the SF-36 scores were also improved in five dimensions including rolephysical,social-functioning,vitality,role-emotional and mental health((74.16±21.25) vs (57.0±39.40),(86.21±13.54) vs (75.54±20.96),(75.16±13.42) vs (64.66±20.54),(78.87±28.36) vs (57.76±46.26),(81.60±16.08) vs (71.20±22.04) respectively,P＜0.05).Conclusion Biofeedback therapy can improve the clinical symptoms,alleviate the moods of anxiety and depression,and improve the quality of life in patients with IBS-C.