lignans and Colitis--Ulcerative

Although magnolol (Mag), an anti-inflammatory natural compound, has been demonstrated to play protective effects on ulcerative colitis (UC), its application as an alternative therapeutic reagent for UC treatment is still greatly impeded due to its poor stability in the gastrointestinal tract and insufficient accumulation in the inflamed colon lesion. Nano-/microsized drug delivery systems can potentially overcome some challenges regarding the oral administration of phytochemicals, which still confront premature early drug release, degradation of NPs, or the sustained drug release of MPs. In this study, we primarily loaded Mag into the core-shell zein-based nanoparticles with chondroitin sulfate coating (Mag@CS-Zein NPs) with an average size of 142.27 ± 5.11 nm, showing significant macrophage-targeting and enhanced colon epithelial cellular uptake capacity. Then, we embedded Mag@CS-Zein NPs into hydrogel microspheres via an electrospraying technology. The Mag@CS-Zein NPsinMPs presented a uniform-sized sphere with an average size of 164.36 ± 6.29 μm and sustained drug-release profiles. Compared to CS-Zein NPs, the developed CS-Zein NPsinMPs exhibited prolonged colon retention on the inflammatory surface, as seen from

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Cell Line, Tumor; Chondroitin Sulfates; Colitis, Ulcerative; Colon; Dextran Sulfate; Drug Carriers; Drug Liberation; Humans; Hydrogels; Lignans; Male; Mice, Inbred ICR; Microspheres; Nanoparticles; Occludin; Zein; Zonula Occludens-1 Protein

Colitis-associated cancer (CAC) has a close relationship with ulcerative colitis (UC). Therapeutic effect of Schisandrin B (SchB) on UC and CAC remains largely unknown. We investigated the preventative effect of SchB on the dextran sulphate sodium (DSS) model of UC and azoxymethane (AOM)/DSS model of CAC. Furthermore, focal adhesion kinase (FAK) activation and influence on commensal microbiota are important for UC treatment. Impact on FAK activation by SchB in UC development was evaluated in vivo and vitro. We also conducted 16S rRNA sequencing to detect regulation of gut microbiota by SchB. Enhanced protection of intestinal epithelial barrier by SchB through activating FAK contributed to protective effect on colon for the fact that protection of SchB can be reversed by inhibition of FAK phosphorylation. Furthermore, influence on gut microbiota by SchB also played a significant role in UC prevention. Our results revealed that SchB was potent to prevent UC by enhancing protection of intestinal epithelial barrier and influence on gut microbiota, which led to inhibition of CAC. SchB was potential to become a new treatment for UC and prevention of CAC.

Topics: Animals; Caco-2 Cells; Colitis, Ulcerative; Colonic Neoplasms; Cyclooctanes; Cytoprotection; Enzyme Activation; Focal Adhesion Protein-Tyrosine Kinases; Gastrointestinal Microbiome; HCT116 Cells; Humans; Intestinal Mucosa; Lignans; Male; Mice; Mice, Inbred C57BL; Permeability; Polycyclic Compounds; Signal Transduction

Magnolol, the main and active ingredient of the Magnolia officinalis, has been widely used in traditional prescription to the human disorders. Magnolol has been proved to have several pharmacological properties including anti-bacterial, anti-oxidant and anti-inflammatory activities. However, the effects of magnolol on ulcerative colitis (UC) have not been reported. The aim of this study was to investigate the protective effects and mechanisms of magnolol on dextran sulphate sodium (DSS)-induced colitis in mice. The results showed that magnolol significantly alleviated DSS-induced body weight loss, disease activities index (DAI), colon length shortening and colonic pathological damage. In addition, magnolol restrained the expression of TNF-α, IL-1β and IL-12 via the regulation of nuclear factor-κB (NF-κB) and Peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways. Magnolol also enhanced the expression of ZO-1 and occludin in DSS-induced mice colonic tissues. These results showed that magnolol played protective effects on DSS-induced colitis and may be an alternative therapeutic reagent for colitis treatment.

Topics: Animals; Biphenyl Compounds; Cecum; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Gastrointestinal Agents; Inflammation; Inflammation Mediators; Intestinal Mucosa; Lignans; Male; Mice; Mice, Inbred C57BL; Occludin; PPAR gamma; Weight Loss

Deoxyschizandrin as one of the most important component of Schisandra chinensis (Turcz.) Baill plays an immunomodulatory role in a variety of diseases, yet its role in ulcerative colitis remains to be elucidated. We aimed to investigate the role of deoxyschizandrin in DSS-induced ulcerative colitis in mice.. In the present study, an inflammation model of cells was constructed to confirm the anti-inflammatory effect of deoxyschizandrin. Then a mouse model with Dextran sulfate sodium sulfate (DSS)-induced ulcerative colitis was constructed, and the effects of deoxyschizandrin on mouse colon inflammation, apoptosis, and CD4 T lymphocyte infiltration in ulcerative colitis were examined.. Deoxyschizandrin could improve the symptoms of ulcerative colitis, determined by hematoxylin-eosin (HE) staining and histopathological scores. Moreover, deoxyschizandrin reduced the levels of inflammatory cytokines, suppressed CD4 T cell infiltration, and effectively inhibited apoptosis in the colon of DSS-induced ulcerative colitis mice.. In summary, deoxyschizandrin can effectively rescue the symptoms of DSS-induced ulcerative colitis in mice by inhibiting inflammation. T cell infiltration and apoptosis in the colon, suggesting that deoxyschizandrin could be a potential drug in treating ulcerative colitis.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; CD4-Positive T-Lymphocytes; Cell Line; Colitis, Ulcerative; Cyclooctanes; Cytokines; Dextran Sulfate; Disease Models, Animal; Female; Gene Expression Regulation; Inflammation; Lignans; Mice; Mice, Inbred C57BL; Polycyclic Compounds

In the colonic mucosa with ulcerative colitis (UC), it has been suggested that L-selectin-peripheral lymph node addressin (PNAd) interaction plays a role in lymphocyte recruitment, which requires PNAd induction on high endothelial venule (HEV)-like vessels. The present study was undertaken to elucidate how these HEV-like vessels participate in the pathogenesis of UC and also to determine whether the presence of such vessels is correlated with clinical outcomes.. Biopsy specimens composed of active (N = 32) and remission (N = 12) phases of UC were subjected to immunohistochemistry for CD34, MECA-79, and HECA-452, and the immunostained sections were quantitatively analyzed. An in vitro binding assay with L-selectin*IgM chimeric protein was carried out to determine whether PNAd on HEV-like vessels formed in UC functions as an L-selectin ligand. RT-PCR was carried out to determine which enzyme is upregulated for PNAd biosynthesis on HEV-like vessels induced in the active phase of UC. Triple immunostaining for MECA-79 together with CD3 and CD20/CD79alpha, CD4 and CD8, or CXCR3 and ST2L was carried out to determine which lymphocyte population closely associates with these vessels.. PNAd-expressing HEV-like vessels were preferentially induced in the active phase of UC with increased transcription of the gene encoding N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1, which directs expression of the MECA-79 epitope. Moreover, T cells, particularly CD4(+) T cells, were more closely associated with these HEV-like vessels than B cells.. T-cell recruitment via PNAd-expressing HEV-like vessels induced by expression of GlcNAc6ST-1 may play a role in UC pathogenesis.

Topics: Antigens, CD34; Antigens, Surface; Biopsy; Carbohydrate Sulfotransferases; Colitis, Ulcerative; Disease Progression; Endothelium, Vascular; Humans; Intestinal Mucosa; L-Selectin; Lignans; Lymphocyte Activation; Membrane Proteins; Receptors, Lymphocyte Homing; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sulfotransferases; T-Lymphocytes; Transcription, Genetic; Up-Regulation; Venules