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      Investigation on Spectrum-Effect Correlation between Constituents Absorbed into Blood and Bioactivities of Baizhu Shaoyao San before and after Processing on Ulcerative Colitis Rats by UHPLC/Q-TOF-MS/MS Coupled with Gray Correlation Analysis

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          Abstract

          Baizhu Shaoyao San (BSS) is a crucial traditional Chinese medicinal formula widely applied for the treatment of painful diarrhea, diarrhea-predominant irritable bowel syndrome, ulcerative colitis, and some other gastrointestinal diseases. Corresponding to the clinical medication, the three medicinal herbs (Atractylodis Macrocephalae Rhizoma, Paeoniae Radix Alba, and Citri Reticulatae Pericarpium) included in BSS should be processed using some specific methods of stir-frying. To find the underlying correlations between serum chemical profiles and curative effects of crude and processed BSS on ulcerative colitis rats, and further explore for the effective material basis of processing, an UHPLC/Q-TOF-MS/MS technique coupled with gray correlation analysis (GCA) was developed. A total of 134 compounds were identified in rat sera after oral administration of BSS, among which 24 compounds were prototypes and 110 compounds were metabolites. Meanwhile, an ulcerative colitis model was established in rats by enema with 2,4,6-trinitrobenzene sulfonic acid, and the pharmacodynamic indicators for drug efficacies were evaluated as well. According to the results, processed BSS showed better efficacy than crude BSS. The top 10 potential effective components with high degree of correlation were identified based on GCA results, which were thought to be the crucial compounds that contributed to the enhancement of therapeutic effects in BSS after processing.

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          Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis.

          Cytokines such as IL-1, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor kappaB (NF-kappaB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NF-kappaB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-alpha concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-kappaB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-kappaB antisense oligonucleotide may be effective in ulcerative colitis.
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            Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology.

            Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate statistical analyses have been employed on mucosal colonic biopsies, colonocytes, lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in order to explore the diagnostic possibilities, define new potential biomarkers, and generate a better understanding of the pathophysiology. Samples were collected from patients with active UC (n = 41), quiescent UC (n = 33), and from controls (n = 25) and analyzed by NMR spectroscopy. Data analysis was carried out by principal component analysis and orthogonal-projection to latent structure-discriminant analysis using the SIMCA P+11 software package (Umetrics, Umea, Sweden) and Matlab environment. Significant differences between controls and active UC were discovered in the metabolic profiles of biopsies and colonocytes. In the biopsies from patients with active UC higher levels of antioxidants and of a range of amino acids, but lower levels of lipid, glycerophosphocholine (GPC), myo-inositol, and betaine were found, whereas the colonocytes only displayed low levels of GPC, myo-inositol and choline. Interestingly, 20% of inactive UC patients had similar profiles to those who were in an active state. This study demonstrates the possibilities of metabonomics as a diagnostic tool in active and quiescent UC and provides new insight into pathophysiologic mechanisms.
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              Anti-inflammatory effects of iridoid glycosides fraction of Folium syringae leaves on TNBS-induced colitis in rats.

              To investigate the effects and the protective mechanism of iridoid glycosides (IG) enriched from Folium syringae leaves on ulcerative colitis (UC) model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. UC in rats was induced by colonic administration with TNBS. IG (80, 160 and 240 mg/kg) was administered for 2 weeks to experimental colitis rats. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured with biochemical methods. The protein expressions of nuclear factor-kappaBp65 (NF-κBp65) and mRNA expressions of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and NF-κBp65, were determined by immunohistochemistry and real-time quantitative PCR, respectively. IG significantly ameliorated macroscopic damage and histological changes, reduced the activity of MPO, depressed MDA and NO levels and effectively inhibited the protein and mRNA expressions of NF-κBp65, TNF-α and IL-6 in the colon tissues of experimental colitis in a dose-dependent manner. Moreover, the effects of IG (160 mg/kg and 240 mg/kg) were superior to salicylazosulfapyridine (150 mg/kg). We demonstrated for the first time that IG possessed marked protective effects on experimental colitis through its antioxidation and inhibiting inflammatory mediators by down-regulation of the expressions of NF-κBp65. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                07 March 2019
                March 2019
                : 24
                : 5
                : 940
                Affiliations
                [1 ]School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; yangyangxu92@ 123456126.com (Y.X.); xl20160806@ 123456126.com (L.X.); duanyu1681@ 123456sina.com (Y.D.); zhoujia19931005@ 123456126.com (J.Z.); 15951921665@ 123456163.com (J.L.); someonearis@ 123456163.com (M.N.); zhangyatingzyt@ 123456126.com (Y.Z.); sonesunfany@ 123456sina.cn (L.S.)
                [2 ]Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China
                [3 ]Institute of Pharmaceutical and Food Engineering, Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China; peike_pk@ 123456126.com
                [4 ]School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China
                Author notes
                [* ]Correspondence: haocai_98@ 123456126.com (H.C.); caogang33@ 123456163.com (G.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-4979-6727
                Article
                molecules-24-00940
                10.3390/molecules24050940
                6429276
                30866532
                0b95ac0d-ec49-4c84-8f5d-72feb7daaf6c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 January 2019
                : 04 March 2019
                Categories
                Article

                baizhu shaoyao san,spectrum-effect correlation,uhplc/q-tof-ms/ms,ulcerative colitis,gray correlation analysis

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