title: Effectiveness of a hydroxynaphthoquinone fraction from Arnebia euchroma in rats with experimental colitis.
abstract: OBJECTIVE
  To evaluate the potential effectiveness of hydroxynaphthoquinone mixture (HM) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.
  
  
  METHODS
  Colitis was induced by intracolonic administration of TNBS (80 mg/kg, dissolved in 50% ethanol). Rats were treated daily for 7 d with HM (2.5, 5, 10 mg/kg) and mesalazine 100 mg/kg 24 h after TNBS instillation. Disease progression was monitored daily by observation of clinical signs and body weight change. At the end of the experiment, macroscopic and histopathologic lesions of rats were scored, and myeloperoxidase (MPO) activity was determined. We also determined inflammatory cytokine tumor necrosis factor (TNF)-α level by ELISA, Western blotting and immunochemistry to explore the potential mechanisms of HM.
  
  
  RESULTS
  After intracolonic instillation of TNBS, animals developed colitis associated with soft stool, diarrhea and marked colonic destruction. Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner. It abrogated body weight loss, diarrhea and inflammation, decreased macroscopic damage score, and improved histological signs, with a significant reduction of inflammatory infiltration, ulcer size and the severity of goblet cell depletion (all P < 0.05 vs TNBS alone group). HM could reduce MPO activity. In addition, it also decreased serum TNF-α level and down-regulated TNF-α expression in colonic tissue. This reduction was statistically significant when the dose of HM was 10 mg/kg (P < 0.05 vs TNBS alone group), and the effect was comparable to that of mesalazine and showed no apparent adverse effect. The underlying mechanism may be associated with TNF-α inhibition.
  
  
  CONCLUSIONS
  These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application.
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Zi-Liang
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Yang
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Lv
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Che
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Hua-Ying Fan, Wei-Wei Song, Ke Liu, Ming-Yan Yang, Xin Che, Hui Xu, School of Pharmacy, Yantai University, Yantai 264005, Shandong Province, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Song
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D028082:Boraginaceae; D003093:Colitis, Ulcerative / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D019804:Mesalamine / Q000494:pharmacology; D009285:Naphthoquinones / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D009285:Naphthoquinones; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase
keywords: 2,4,6-trinitrobenzene sulfonic acid-induced colitis; Arnebia euchroma (Royle) Johnst; Hydroxynaphthoquinones; Inflammatory bowel disease; Tumor necrosis factor