peoniflorin and Irritable-Bowel-Syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD).. To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats.. Sixty male Sprague-Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing.. In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration. Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (. PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.

Topics: Animals; Irritable Bowel Syndrome; Lactates; Male; NF-kappa B; Occludin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Rodent Diseases; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

SiNiSan (SNS) is an ancient Chinese herbal prescription, and the current clinical treatment of irritable bowel syndrome (IBS) is effective. In the previous study of the research team, the multi-functional co-synergism of SNS against IBS was presented. Some potential drug targets and candidate ligands were predicted.. This study attempts to explore the crucial ingredient combinations from SNS formula and reveal their synergistic mechanism for IBS therapy.. In present study, a comprehensive strategy was performed to reveal IBS related pathways and biological modules, and explore synergistic effects of the ingredients, including ADME (absorption, distribution, metabolism, excretion) screening, Text mining, Venn analysis, Gene ontology (GO) analysis, Pathway cluster analysis, Molecular docking, Network construction and Experimental verification in visceral hypersensitivity (VHS) rats.. Three compressed IBS signal pathways were derived from ClueGO KEGG analysis of 63 IBS genes, including Neuroactive ligand-receptor interaction, Inflammatory mediator regulation of TRP (transient receptor potential) channels and Serotonergic synapse. A multi-module network, composed of four IBS therapeutic modules (psychological, inflammation, neuroendocrine and cross-talk modules), was revealed by Target-Pathway network. Nine kernel targets were considered closely associated with the IBS pathways, including ADRA2A, HTR2A, F2RL1, F2RL3, TRPV1, PKC, PKA, IL-1Β and NGF. In silico analysis revealed that three crucial ingredients (synephrine, paeoniflorin and naringin) were assumed to coordinate the network of those IBS therapeutic modules by acting on these kernel targets in the important pathways. In vivo experimental results showed that the crucial ingredient combinations synergistically affected the expressions of the kernel biological molecules, and improved the minimum capacity threshold of AWR in VHS rats.. The study proposes the important IBS associated pathways and the network regulation mechanisms of the crucial ingredients. It reveals the multi-target synergistic effect of the crucial ingredient combinations for the novel therapy on IBS.

Topics: Animals; Data Mining; Drugs, Chinese Herbal; Flavanones; Glucosides; Humans; Inflammation; Interleukin-6; Irritable Bowel Syndrome; Male; Molecular Docking Simulation; Monoterpenes; Proto-Oncogene Proteins c-raf; Rats, Sprague-Dawley; Signal Transduction; Synephrine; Transient Receptor Potential Channels

SiNiSan (SNS) is a traditional Chinese medicine (TCM) prescription that has been widely used in the clinical treatment of irritable bowel syndrome (IBS). However, the underlying active substances and molecular mechanisms remain obscure.. A bioinformatics/topology based strategy was proposed for identification of the drug targets, therapeutic agents and molecular mechanisms of SiNiSan against irritable bowel syndrome.. In this work, a bioinformatics/network topology based strategy was employed by integrating ADME filtering, text mining, bioinformatics, network topology, Venn analysis and molecular docking to uncover systematically the multicomponent synergy mechanisms. In vivo experimental validation was executed in a Visceral Hypersensitivity (VHS) rat model.. 76 protein targets and 109 active components of SNS were identified. Bioinformatics analysis revealed that 116 disease pathways associated with IBS therapy could be classified into the 19 statistically enriched functional sub-groups. The multi-functional co-synergism of SNS against IBS were predicted, including inflammatory reaction regulation, oxidative-stress depression regulation and hormone and immune regulation. The multi-component synergetic effects were also revealed on the herbal combination of SNS. The hub-bottleneck genes of the protein networks including PTGS2, CALM2, NOS2, SLC6A3 and MAOB, MAOA, CREB1 could become potential drug targets and Paeoniflorin, Naringin, Glycyrrhizic acid may be candidate agents. Experimental results showed that the potential mechanisms of SiNiSan treatment involved in the suppression of activation of Dopaminergic synapse and Amphetamine addiction signaling pathways, which are congruent with the prediction by the systematic approach.. The integrative investigation based on bioinformatics/network topology strategy may elaborate the multicomponent synergy mechanisms of SNS against IBS and provide the way out to develop new combination medicines for IBS.

Topics: Animals; Computational Biology; Data Mining; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Synergism; Drugs, Chinese Herbal; Flavanones; Glucosides; Humans; Irritable Bowel Syndrome; Male; Medicine, Chinese Traditional; Molecular Docking Simulation; Monoterpenes; Protein Interaction Maps; Proteins; Rats, Sprague-Dawley; Signal Transduction

Zhi-Shao-San (ZSS), a traditional Chinese medicinal prescription, has been clinically used for the treatment of irritable bowel syndrome (IBS) for centuries. A comparative study was designed and conducted to compare the pharmacokinetic differences between paeoniflorin naringin, hesperidin and neohesperidin after oral administration of ZSS decoction to normal rats and IBS rats induced by acetic acid and restraint stress. Further, an efficient, sensitive and selective liquid chromatography/tandem mass spectrometry for the simultaneous determination of four analytes of ZSS decoction in rat plasma was developed and validated. The validated method was successfully applied to comparison of pharmacokinetic profiles of analytes in rat plasma. The results showed that the absorptions of naringin, hesperidin and neohesperidin in IBS group were all significantly higher than those in normal group and no obvious difference was seen for paeoniflorin between the two groups, which is helpful for improving clinical therapeutic efficacy and further pharmacological studies of ZSS.

Topics: Animals; Chromatography, Liquid; Drug Stability; Drugs, Chinese Herbal; Flavanones; Glucosides; Irritable Bowel Syndrome; Linear Models; Male; Monoterpenes; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry