title: Protective effect of total alkaloids of Sophora alopecuroides on dextran sulfate sodium-induced chronic colitis.
abstract: OBJECTIVE
  To investigate the effect of total alkaloids of Sophora alopecuroides (TASA) on dextran sulfate sodium (DSS)-induced colitis in mice.
  
  
  METHODS
  Chronic experimental colitis was induced by administration of 4 cycles of 4% DSS. Fifty mice were randomly distributed into 4 groups (normal, DSS, DSS/high-dose TASA, and DSS/low-dose TASA groups) by a random number table with body weight stratification. Mice in the normal group (n=11) and DSS-induced colitis control group (n=15) received control treatment of 20 mL/kg distilled water; DSS plus TASA high- and low-dose groups (n=12 each) were treated with TASA solution (20 mL/kg) at the doses of 60 mg/kg and 30 mg/kg, respectively. The severity of colitis was assessed on the basis of clinical signs, colon length, and histology scores. Moreover, secretory immunoglobulin A (sIgA) and haptoglobin (HP) were analyzed by enzyme linked immunosorbent assay; intercellular adhesion molecule 1 (ICAM-1) and macrophage-migration inhibitory factor (MIF) gene expressions were analyzed by quantitative reverse transcriptase realtime polymerase chain reaction (qRT-PCR) using SYBA green I; and nuclear factor κ B (NF-κ B) expression and activation and p65 interaction with the promoter of ICAM-1 gene were assessed by Western blotting and chromatin immunoprecipitation assay.
  
  
  RESULTS
  TASA administration significantly attenuated the damage and substantially reduced HP elevation and maintained the level of cecum sIgA. TASA inhibited the ICAM-1 gene expression and had no effect on MIF gene expression. Also, TASA was able to reduce phospho-I κ B α (p-I κ B α) protein expression; however, it had no effect on the activation of I κ B kinase α (IKK α) and inhibitor of NF-κ B α (I κ B α). Moreover, TASA inhibited the p65 recruitment to the ICAM-1 gene promoter.
  
  
  CONCLUSIONS
  TASA had a protective effect on DSS-induced colitis. Such effect may be associated with its inhibition of NF-κ B activation and blockade of NF-κ B-regulated transcription activation of proinflammatory mediator gene.
authors.affiliation: School of Pharmacy, Guangdong Medical College, Dongguan, Guangdong Province, China.
authors.forename: Wen-chang
authors.initials: WC
authors.lastname: Zhao
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Song
authors.forename: Hong-zhu
authors.initials: HZ
authors.lastname: Deng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000473:pathology / Q000648:ultrastructure; D016264:Dextran Sulfate; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D011401:Promoter Regions, Genetic / Q000235:genetics; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000737:chemistry*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000470:Alkaloids; D006242:Haptoglobins; D020672:I-kappa B Proteins; D007071:Immunoglobulin A, Secretory; D008263:Macrophage Migration-Inhibitory Factors; C000606205:Nfkbia protein, mouse; D020011:Protective Agents; D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D016264:Dextran Sulfate