Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9318
Revised: October 16, 2013
Accepted: November 1, 2013
Published online: December 28, 2013
AIM: 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.
CONCLUSION: These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application.
Core tip: Current therapies for inflammatory bowel disease are limited by lack of effectiveness, drug refractoriness or severe adverse effects. Therefore, there is an urgent need for more effective and safe therapeutic approaches. Due to their favourable effect and less side effects, looking for novel agents from herbal and natural products has been a research focus for a long time. Previous studies demonstrate that hydroxynaphthoquinones exert therapeutic action on chronic inflammatory disease. In this study, hydroxynaphthoquinones showed beneficial effect on 2,4,6-trinitrobenzene sulfonic acid-induced colitis via tumor necrosis factor-α inhibition, and the effect was comparable to that of mesalazine. This provides pharmacological evidence for its clinical application.