QingChang-XiaoPi decoction ameliorates intestinal inflammation of ulcerative colitis by regulating the pathogenicity of Th17 cells.

BACKGROUND: QingChang-XiaoPi Decoction (QCXPY), a Chinese herbal prescription, has been employed in the treatment of ulcerative colitis (UC) in China. However, its molecular mechanism of action in UC remains unclear. PURPOSE: To elucidate the therapeutic effects of QCXPY against UC and reveal its mechanism of action. STUDY DESIGN: We conducted a single-arm observation to evaluate the clinical efficacy of QCXPY in patients with mild-to-moderate UC. Inclusion and exclusion criteria were established to ensure the eligibility of participants, with a focus on excluding patients with specific conditions or complications that could confound the results. METHODS: The expression of inflammatory factors in patients' serum was detected using a Luminex assay. The main components of QCXPY were identified using UHPLC-Q-TOF-MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. The efficacy of QCXPY was evaluated using a dextran sulfate sodium (DSS)-induced mouse model. Disease activity index (DAI), histopathological score, cytokine detection by ELISA, T-helper 17 (Th17) cell proportion by flow cytometry, expression of the IL-23/IL-17 axis, and changes in the levels of its downstream effectors were detected by immunohistochemistry, immunofluorescence, and western blotting. RESULTS: QCXPY could alleviate the symptoms of diarrhea, abdominal pain, abdominal distension, and purulent stool in patients with mild-to-moderate UC. Moreover, it reduced the expression of IL-6, IL-17, and IL-23 in serum; alleviated DSS-induced experimental colitis in mice; reduced DAI, pathological scores, and the expressions of IL-6, IL-17, and IL-23 in colon tissue; and decreased the proportion of pathogenic Th17 cells and the expression of STAT3 and phospho-STAT3. CONCLUSION: This study confirmed for the first time that QCXPY could alleviate intestinal symptoms, reduce the levels of serum inflammatory factors, and improve the quality of life of patients with mild-to-moderate UC. Its mechanism of action may involve reducing the secretion of inflammatory cytokines, moderating the pathogenicity of Th17 cells, and inhibiting STAT3 phosphorylation, thereby alleviating intestinal inflammation in UC.

The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.

Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D. IMPORTANCE: Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.

Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis.

Evidence of the advantages of Coptidis Rhizoma (CR) for the treatment of ulcerative colitis (UC) is accumulating. However, research revealing the targets and molecular mechanisms of CR against UC is scarce. In this research, a bioinformatics analysis was performed to carry out the physicochemical properties and biological activities of phytochemicals in CR and analyze the binding activities, targets, biological functions and mechanisms of CR against UC. This research shows that the CR's key phytochemicals, which are named Coptisine, Berberrubine, Berlambine, Berberine, Epiberberine, Obacunone, Worenine, Quercetin, (R)-Canadine, Magnograndiolide, Palmatine and Moupinamide, have ideal physicochemical properties and bioactivity. A total of 1,904 potential phytochemical targets and 17,995 UC-related targets are identified, and we finally acquire 233 intersection targets between key phytochemicals and disease. A protein-protein interaction network of 233 common targets was constructed; and six hub targets were acquired with a degree greater than or equal to median, namely TP53, HSP90AA1, STAT3, ESR1, MYC, and RELA. The enrichment analysis suggested that the core targets may exert an impact on anti-inflammatory, immunoregulatory, anti-oxidant and anti-fibrosis functions mainly through the PI3K/ART signaling pathway, Th17 differentiation signaling pathway, inflammatory bowel disease signaling pathway, etcetera. Also, a molecular docking analysis shows that the key phytochemicals have strong affinity for binding to the core targets. Finally, the interaction network of CR, phytochemicals, targets, GO functions, KEGG pathways and UC is constructed. This study indicates that the key phytochemicals in CR have superior drug likeness and bioactivity, and the molecular mechanism of key phytochemicals against UC may be via the signaling pathway mentioned above. The potential and critical pharmacological mechanisms provide a direction for future research.

Genomic constitution and intergenomic translocations in the Elymus dahuricus complex revealed by multicolor GISH.

Multicolor genomic in situ hybridization was used to investigate the genomic constitution and intergenomic translocations in the Elymus dahuricus complex. The genomic constitution of species of the E. dahuricus complex was confirmed as StYH. H/Y and H/St intergenomic translocations were identified in the present study, with 7H and 1Y chromosomes involved in reciprocal translocations for all the accessions investigated in the complex. We propose that the translocations in the E. dahuricus complex are species-specific, associated with allopolyploidy, and may serve as important structural alterations for allopolyploid stability. Furthermore, they may help to restore fertility and nucleocytoplasmic compatibility in a newly formed polyploid and facilitate the successful establishment of E. dahuricus as a stable species. It was found that more chromosomes were involved in translocations and more types of intergenomic translocations were observed in the high altitude (4150 m) population Y 2228 than in populations from relatively lower altitudes (2600-3800 m). We speculate that more complicated genomic changes were associated with escalating altitudes in the Tibetan Plateau. These genomic changes contribute to promote the genetic variability and enable the newly formed allopolyploids to adapt to more changeable and harsher environments during the evolution of a polyploid species, thus facilitating their rapid and successful establishment in nature.

[The study of the pro-nucleating activity of bacteria identified in cholesterol gallstones in model bile systems].

OBJECTIVE: To explore the relationship of bacteria identified in cholesterol gallstones and gallstone formation. METHODS: Observe the bacteria activity in model bile and the influence of bacteria on the cholesterol nucleation time (NT). RESULTS: (1) Model bile were suitable for the growth of E. coli, Pseudomonas aeruginosa, staphylococcus aureus, enterococcus faecalis, clostridium difficile and Clostridium. Propionibacterium acne grew weakly and the growth of Bacteroides fragilis was restrained in model bile. (2) Only pseudomonas aeruginosa and enTerococcus faecalis could ly shorten the cholesterol nucleation time. (3) With pseudomonas aeruginosa or enTerococcus faecalis added in model bile, the formation of cholesterol crystals presented a progressive course of evolution. CONCLUSIONS: Pseudomonas aeruginosa and enterococcus faecalis, not propionibacterium acne, have pro-nucleating ability in model bile.