OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan/adverse effects* ; Aspartic Acid ; Dextrans/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Colitis/drug therapy* ; Biomarkers/metabolism* ; Amino Acids/adverse effects* ; Glycerophospholipids/therapeutic use* ; Sphingolipids/adverse effects* ; Bile Acids and Salts/adverse effects* ; Glutamates/adverse effects* ; Alanine/adverse effects* ; Arachidonic Acids/adverse effects* ; Linoleic Acids/adverse effects* ; Terpenes

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and polyethylene glycol (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possesses super hydrophilicity with hydrogel grafting. The evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.
Allyl Compounds ; Animals ; Biocompatible Materials ; Catheters ; Dextrans ; Hydrogel, Polyethylene Glycol Dimethacrylate ; Hydrogels ; Hydrophobic and Hydrophilic Interactions ; Isocyanates ; Polyethylene Glycols ; Rats ; Water

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.
Angelica ; Cell Culture Techniques ; Colitis ; Colitis, Ulcerative ; Colon ; Dextrans ; Interleukin-17 ; Medicine, Korean Traditional ; Neutrophils ; Plants ; Sodium ; T-Lymphocytes ; Th17 Cells ; Weight Loss

BACKGROUND/AIMS: The current study aims to investigate the protective effects of Bifidobacterium infantis on the abnormal immune response to inflammatory bowel disease (IBD) in dextran sodium sulfate (DSS)-induced colitis. METHODS: Eight-week-old BALB/c mice were separated into five groups at random (control, DSS, DSS+B9 [B. infantis 1×10⁹ CFU], DSS+B8 [B. infantis 1×10⁸ CFU], and DSS+B7 [B. infantis 1×10⁷ CFU]). Colitis was induced by 5% DSS ad libitum for 7 days, at which time we assessed weight, the disease activity index (DAI) score, and the histological damage score. The nuclear transcription factor Foxp3 (a marker of Treg cells), cytokines interleukin-10 (IL-10) and transforming growth factor β1 (TGF-β1), and related proteins (programmed cell death ligand 1 [PD-L1] and programmed cell death 1 [PD-1]) were detected by an immunohistochemical method and Western blot. RESULTS: B. infantis increased weight, decreased DAI scores and histological damage scores, increased the protein expression of Foxp3 (p<0.05) and cytokines IL-10 and TGF-β1 in mouse colon tissue (p<0.05), and increased the expression of PD-L1 in the treatment groups relative to that in the DSS group (p<0.05). The effect of B. infantis on Foxp3 and PD-L1 was dose dependent in the treatment groups (p<0.05). PD-L1 was positively correlated with Foxp3, IL-10, and TGF-β1. CONCLUSIONS: In a mouse model of IBD, B. infantis can alleviate intestinal epithelial injury and maintain intestinal immune tolerance and thus may have potential therapeutic value for the treatment of immune damage in IBD.
Animals ; Bifidobacterium ; Blotting, Western ; Cell Death ; Colitis ; Colon ; Cytokines ; Dextrans ; Immune Tolerance ; Inflammatory Bowel Diseases ; Interleukin-10 ; Methods ; Mice ; Models, Theoretical ; Sodium ; T-Lymphocytes, Regulatory ; Transcription Factors ; Transforming Growth Factors

BACKGROUND: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized. METHODS: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured. RESULTS: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric. CONCLUSIONS: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.
Adenosine Triphosphate ; Animals ; Asian Continental Ancestry Group ; Blotting, Western ; Carcinogenesis ; Colitis ; Colon ; Curcuma ; Curcumin ; Cyclin D1 ; Cyclooxygenase 2 ; Dextran Sulfate ; Dextrans ; DNA ; Drinking Water ; Herbal Medicine ; Humans ; Inflammatory Bowel Diseases ; Mice ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Plants ; Scutellaria baicalensis

BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
Animals ; Blotting, Western ; Chloride Channels ; Colitis ; Colon ; Dextrans ; Down-Regulation ; In Vitro Techniques ; Interstitial Cells of Cajal ; Mice ; Muscle, Smooth ; Myoelectric Complex, Migrating ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Polymerase Chain Reaction ; RNA, Messenger ; Sodium

Tetrodes, consisting of four twisted micro-wires can simultaneously record the number of neurons in the brain. To improve the quality of neuronal activity detection, the tetrode tips should be modified to increase the surface area and lower the impedance properties. In this study, tetrode tips were modified by the electrodeposition of Au nanoparticles (AuNPs) and dextran (Dex) doped poly (3,4-ethylenedioxythiophene) (PEDOT). The electrochemical properties were measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A decrease in the impedance value from 4.3 MΩ to 13 kΩ at 1 kHz was achieved by the modified tetrodes. The cathodic charge storage capacity (CSC(C)) of AuNPs-PEDOT deposited tetrodes was 4.5 mC/cm², as determined by CV measurements. The tetrodes that were electroplated with AuNPs and PEDOT exhibited an increased surface area, which reduced the tetrode impedance. In vivo recording in the ventral posterior medial (VPM) nucleus of the thalamus was performed to investigate the single-unit activity in normal rats. To evaluate the recording performance of modified tetrodes, spontaneous spike signals were recorded. The values of the L-ratio, isolation distance and signal-to-noise (SNR) confirmed that electroplating the tetrode surface with AuNPs and PEDOT improved the recording performance, and these parameters could be used to effectively quantify the spikes of each cluster.
Animals ; Brain ; Dextrans ; Dielectric Spectroscopy ; Electric Impedance ; Electrodes ; Electroplating ; Microelectrodes ; Nanoparticles* ; Neurons ; Rats ; Thalamus

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines TNF-α and IL-6 and inflammatory lipid mediators, prostaglandin E₂ and leukotriene B₄. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed IκB phosphorylation, nuclear translocation of nuclear factor κB (NF-κB), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of TNF-α, IL-6 and IL-13 and also hindered phosphorylation of NF-κB and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF-α and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.
Adenine Nucleotides ; Adenine* ; Animals ; Bone Marrow ; Cell Line ; Cell Wall ; Colitis ; Cytokines ; Dextrans ; Gram-Negative Bacteria ; Hypersensitivity ; Inflammation ; Interleukin-13 ; Interleukin-6 ; Lymphocytes ; Macrophages ; Mammals ; Mast Cells ; Mice ; Mitogen-Activated Protein Kinases ; Nucleic Acids ; Peritoneal Cavity ; Phosphorylation ; Protein Kinases ; Sodium ; Toll-Like Receptor 4

Chronic inflammation is a major etiology of cancer. Accumulating epidemiological and experimental evidences suggest that intake of high protein diet (HPD) is associated with colitis-associated colon cancer, however, most of the studies were confined in colon. Systemic influence of HPD on inflammation indices in different tissues of an organism has never been studied. We therefore investigated the effect of HPD on mouse skin and colonic inflammation using the well characterized inflammation induction protocol in both tissues (12-O-tetradecanoylphorbol-13-acetate [TPA] for skin and dextran sodium sulfate [DSS] for colon). ICR mice were grouped to normal diet (ND, 20% casein) or HPD (50% casein) groups. In each diet group, mice were treated with either vehicle (acetone or H₂O), TPA, TPA and DSS, or DSS. Experimental diet was fed for total 4 weeks. After 1 week of diet feeding, 6.5 nmol of TPA was topically applied twice a week for 2 weeks on the shaved mouse dorsal skin. Drinking water containing 2% DSS was administered for 7 days at the final week of experiment. The results showed that TPA-induced skin hyperplasia, epidermal cell proliferation, and cyclooxygenase-2 (COX-2) expression were reduced in HPD group compared to ND group. In contrast, HPD increased DSS-induced colon mucosal hyperplasia, colonocyte proliferation, COX-2 expression, and plasma nitric oxide compared to ND group. This suggests that HPD exerts differential effect on different tissue inflammation which implies efficacy of protein intervention to human also should be monitored more thoroughly.
Animals ; Cell Proliferation ; Colon ; Colonic Neoplasms ; Cyclooxygenase 2 ; Dextrans ; Diet ; Dietary Proteins ; Drinking Water ; Humans ; Hyperplasia ; Inflammation ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; Plasma ; Skin ; Sodium

BACKGROUND: Curcumin, a yellow ingredient of turmeric (Curcuma longa Linn, Zingiberaceae), has long been used in traditional folk medicine in the management of inflammatory disorders. Although curcumin has been reported to inhibit experimentally-induced colitis and carcinogenesis, the underlying molecular mechanisms remain largely unresolved. METHODS: Murine colitis was induced by dextran sulfate sodium (DSS) which mimics inflammatory bowel disease. Curcumin or tetrahydrocurcumin was given orally (0.1 or 0.25 mmol/kg body weight daily) for 7 days before and together with DSS administration (3% in tap water). Collected colon tissue was used for histologic and biochemical analyses. RESULTS: Administration of curcumin significantly attenuated the severity of DSS-induced colitis and the activation of NF-κB and STAT3 as well as expression of COX-2 and inducible nitric oxide synthase. In contrast to curcumin, its non-electrophilic analogue, tetrahydrocurcumin has much weaker inhibitory effects. CONCLUSIONS: Intragastric administration of curcumin inhibited the experimentally induced murine colitis, which was associated with inhibition of pro-inflammatory signaling mediated by NF-κB and STAT3.
Animals ; Body Weight ; Carcinogenesis ; Colitis ; Colon ; Curcuma ; Curcumin ; Dextran Sulfate ; Dextrans ; Inflammatory Bowel Diseases ; Medicine, Traditional ; Mice ; Nitric Oxide Synthase Type II