title: Active components alignment of Gegenqinlian decoction protects ulcerative colitis by attenuating inflammatory and oxidative stress.
abstract: BACKGROUND
  Gegenqinlian Decoction (GQD) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. It has significant treatment efficacy for patients with inflammatory bowel disease (IBD). We analyzed and showed that the active components alignment of Gegenqinlian Decoction (ACAG) possesses broad pharmacological effects including analgesic, antipyretic, anti-inflammatory, antibacterial, antiviral and antidiarrhea, as well as the effect of adjusting gastrointestinal function in our preliminary experiments. However, the exact molecular mechanisms on how ACAG exerts these pharmacological effects still remain elusive. In the present study, the plausible pharmacological effects of ACAG on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated.
  
  
  METHODS
  Male Sprague-Dawley (SD) rats with TNBS/ethanol-induced colitis were used. The colonic wet weight, macroscopic and histological colon injury, superoxide dismutase (SOD), malonyldialdehyde (MDA), and inducible nitric oxide synthase (iNOS) activity were observed. Pro-inflammation cytokines were determined by ELISA methods, semi-quantitative RT-PCR and Immuno-histochemistry.
  
  
  RESULTS
  We showed administration of ACAG was able to improve colitis. This was manifested by a decreased in the score of macroscopic and histological colonic injury, by lowered colonic wet weight, accompanied by significant increased of SOD activity, and decreased of MDA and iNOS activities. The treatment also significantly reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels in colon and serum as well as the colonic mRNA levels for several inflammatory cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), macrophage inflammatory protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1) and toll-like receptor 2, 4 (TLR2, TLR4). In addition, we also showed that ACAG was able to inhibit the activation and translocation of transcription factors, nuclear factor kappaBp65 (NF-κBp65) in colon.
  
  
  CONCLUSIONS
  Our results suggest that ACAG exhibits protective effect in TNBS-induced ulcerative colitis. We postulate that this might be due to its modulation of oxidant/anti-oxidant balance, downregulation of productions, expressions of pro-inflammatory cytokines and inhibition of NF-κBp65 signal transduction pathways.
authors.affiliation: Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, Heilongjiang, PR China; School of Pharmacy, Harbin University of Commerce, Harbin 150076, Heilongjiang, PR China.
authors.forename: Bei-Lei
authors.initials: BL
authors.lastname: Xu
authors.affiliation: School of Chinese Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, Beijing, PR China. Electronic address: guijunzhang@163.com.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: Zhang
authors.affiliation: Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, Heilongjiang, PR China.
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Ji
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D004365:Drugs, Chinese Herbal; C542794:gegenqinlian; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase
keywords: Active components alignment of Gegenqinlian Decoction (ACAG); ELISA; Immuno-histochemistry; Nuclear factor-kappa B; Semi-quantitative RT-PCR; TNBS-induced colitis