Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/ß-catenin signaling pathway.

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis.

Ulcerative colitis (UC) is a chronic and immune-mediated inflammatory disorder characterized by abdominal pain, diarrhoea, and haematochezia. The goal of clinical therapy for UC is mucosal healing, accomplished by regenerating and repairing the intestinal epithelium. Paeoniflorin (PF) is a natural ingredient extracted from Paeonia lactiflora that has significant anti-inflammatory and immunoregulatory efficacy. In this study, we investigated how PF could regulate the renewal and differentiation of intestinal stem cells (ISCs) to improve the regeneration and repair of the intestinal epithelium in UC. Our experimental results showed that PF significantly alleviated colitis induced by dextran sulfate sodium (DSS) and ameliorated intestinal mucosal injury by regulating the renewal and differentiation of ISCs. The mechanism by which PF regulates ISCs was confirmed to be through PI3K-AKT-mTOR signalling. In vitro, we found that PF not only improved the growth of TNF-α-induced colon organoids but also increased the expression of genes and proteins related to the differentiation and regeneration of ISCs. Furthermore, PF promoted the repair ability of lipopolysaccharide (LPS)-induced IEC-6 cells. The mechanism by which PF regulates ISCs was further confirmed and was consistent with the in vivo results. Overall, these findings demonstrate that PF accelerates epithelial regeneration and repair by promoting the renewal and differentiation of ISCs, suggesting that PF treatment may be beneficial to mucosal healing in UC patients.

[Study on medication regularity of chronic atrophic gastritis in Beijing-Tianjin-Hebei region based on latent structure model].

To explore the etiology, pathogenesis, distribution of syndromes and the rule of medication of chronic atrophic gastritis(CAG) in Beijing-Tianjin-Hebei region based on the latent structure model. Chronic atrophic gastritis of 279 cases in Beijing-Tianjin-Hebei region were extracted from the established database of spleen and stomach diseases of famous veteran Chinese medicine experts. The latent structure models of symptoms and drugs of chronic atrophic gastritis were constructed by using Lantern 3.1.2 software, and the latent structure models were interpreted. SAS 10.0 software was used to mine association rules of drugs and symptoms. The constitutional characteristics of patients with chronic atrophic gastritis in Beijing-Tianjin-Hebei region were "turbid toxin and damaging Yin". The common syndromes were turbid toxin, deficiency of stomach Yin, stagnation of liver and stomach, stagnation of liver and stomach Qi, obstruction of stomach collaterals and blood stasis, and weakness of spleen and stomach. Common medicines are Lobeliae Chinensis Herba, Scutellariae Barbatae Herba, Amomi Fructus Rotundus, Amomi Fructus, Poria, Isatidis Radix, Artemisiae Scopariae Herba, Scorpio, Coptidis Rhizoma, Lilii Bulbus, Linderae Radix, Phragmitis Rhizoma, Ophiopogonis Radix, Pogostemonis Herba, Eupatorii Herba, Magnoliae Officinalis Cortex, Aurantii Fructus Immaturus. Common prescriptions are Baihe Wuyao Powder, Danggui Shaoyao Powder, Xiaoyao Pills, Xiangsu Powder, Dachengqi Decoction, Zuojin Pills, Qingzhong Decoction, Zhishi Daozhi Pills, etc. The application of latent structure model and correlation analysis in the empirical study of famous and veteran Chinese medicine experts is in line with the research direction of modern Chinese medicine "traditional Chinese medicine + X". The conclusions obtained effectively tap the experience of famous and veteran TCM experts, and provide a data and visual clinical reference and prescription compatibility for young TCM physicians in the treatment of chronic atrophic gastritis based on syndrome differentiation.

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis.

AIM: To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 µg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ. CONCLUSION: Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.

Identification and characterization of an anti-fibrotic benzopyran compound isolated from mangrove-derived Streptomyces xiamenensis.

An anti-fibrotic compound produced by Streptomycesn xiamenensis, found in mangrove sediments, was investigated for possible therapeutic effects against fibrosis. The compound, N-[[3,4-dihydro-3S-hydroxy-2S-methyl-2-(4'R-methyl-3'S-pentenyl)-2H-1-benzopyran-6-yl]carbonyl]-threonine (1), was isolated from crude extracts and its structure, including the absolute configuration was determined by extensive spectroscopic data analyses, Mosher's method, Marfey's reagent and quantum mechanical calculations. In terms of biological effects, this compound inhibits the proliferation of human lung fibroblasts (WI26), blocks adhesion of human acute monocytic leukemia cells (THP-1) to a monolayer of WI26 cells, and reduces the contractile capacity of WI26 cells in three-dimensional free-floating collagen gels. Altogether, these data indicate that we have identified a bioactive alkaloid (1) with multiple inhibitory biological effects on lung excessive fibrotic characteristics, that are likely involved in fibrosis, suggesting that this molecule might indeed have therapeutic potential against fibrosis.