title: Combined Therapy with Rheum tanguticum Polysaccharide and Low-dose 5-ASA Ameliorates TNBS-Induced Colitis in Rats by Suppression of NF-κB.
abstract: The most common conventional therapy for inflammatory bowel disease in clinical practice involves the use of nonsteroidal anti-inflammatory drugs, such as 5-amino salicylic acid. However, a high dose of 5-amino salicylic acid may bring about severe side effects. Chinese people have used Rheum tanguticum as a folk remedy for gastrointestinal disease for two thousand years. Our group has isolated R. tanguticum polysaccharide 1 from R. tanguticum and verified that it can attenuate 2,4,6-trinitrobenzene sulfonic acid-induced colitis in murines/rats. The present study aims to evaluate whether the addition of R. tanguticum polysaccharide 1 can improve efficacy and limit subsequent side effects of conventional treatment (5-amino salicylic acid) in rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Sixty Sprague-Dawley male rats were randomized into five groups and treated with (1) saline (saline, 0.2 mL/day × 5, p. o.), (2) 2,4,6-trinitrobenzene sulfonic acid alone (saline, 0.2 mL/day × 5, p. o.), (3) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid (5-amino salicylic acid, 75 mg/kg/day × 5, p.o), (4) 2,4,6-trinitrobenzene sulfonic acid + R. tanguticum polysaccharide 1 (R. tanguticum polysaccharide 1, 200 mg/kg/day × 5, p. o.), and (5) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 (5-amino salicylic acid, 25 mg/kg/day × 5, p.o; R. tanguticum polysaccharide 1, 200 mg/kg/day × 5, p. o.). All the rats were sacrificed on the 6th day after treatment using an overdose of anesthesia. A histological assessment was performed using semiquantitative scores; nuclear factor-kappa B and tumor necrosis factor-α were measured with Western blot, cyclooxygenase 1 and cyclooxygenase 2 protein expressions were investigated by RT-polymerase chain reaction, and prostoglandin E2 and inducible nitric oxide synthase productions were investigated by ELISA. The extent and severity of histological signs were attenuated significantly in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group. Treatment with R. tanguticum polysaccharide 1 plus 5-amino salicylic acid markedly decreased nuclear factor-kappa Bp65 and tumor necrosis factor-α protein expressions. R. tanguticum polysaccharide 1 and 5-amino salicylic acid had no effect on cyclooxygenase 1 protein expression, but inhibited the overexpression of the cyclooxygenase 2 protein. After treatment with 5-amino salicylic acid and R. tanguticum polysaccharide 1, the prostoglandin E2 level increased significantly and the inducible nitric oxide synthase level decreased considerably in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group compared with the 2,4,6-trinitrobenzene sulfonic acid alone group. These results demonstrate that combined therapy with R. tanguticum polysaccharide 1 and low-dose 5-amino salicylic acid had more favorable effects on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats, and its effects may be associated with inhibiting nuclear factor-kappa Bp65 protein expression and tumor necrosis factor-α production, resulting in a decrease of cyclooxygenase 2 and inducible nitric oxide synthase protein expressions.
authors.affiliation: Department of Pharmaceutical, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Linna
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhenxiong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry*; D014301:Trinitrobenzenes / Q000009:adverse effects; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D011134:Polysaccharides; D014301:Trinitrobenzenes; D014409:Tumor Necrosis Factor-alpha; C029222:sym-trinitrobenzene; D014302:Trinitrobenzenesulfonic Acid; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2