The correlation between NF-κB inhibition and disease activity by coadministration of silibinin and ursodeoxycholic acid in experimental colitis.

Abstract

NF-κB is one of the most important nuclear factors responsible for overexpression of proinflammatory cytokines. This is demonstrated by increased NF-κB activity and other dependent immune factors in inflammatory bowel disease (IBD). Anti-inflammatory effects of silibinin and ursodeoxycholic acid (UDCA) along with their NF-κB inhibitory property are thought to be beneficial in colitis. Trinitrobenzene sulfonic acid was used to induce colitis rat models. After instillation, 48 rats were treated with oral silibinin, UDCA alone or a combination of both. Intraperitoneal dexamethasone was used in the control group. After 12 days of treatment, colonic samples were tested for the severity of mucosal damage macroscopically and microscopically. The levels of activated NF-κB, IL-1β, TNF-α, myeloperoxidase, thiobarbituric acid reactive substances (TBARS), protein carbonyl, and the antioxidant power of the bowel homogenates were determined. The results indicated a significant reduction in NF-κB activity as well as the levels of IL-1β, TNF-α, TBARS, protein carbonyl, myeloperoxidase activity, and an improvement in antioxidant power of colitis in treated rats. Combination therapy resulted in a more prominent improvement in bowel antioxidant power and myeloperoxidase activity. In conclusion, combination of silibinin and UDCA by inhibition of NF-κB and other relevant inflammatory factors of colitis is a good candidate for management of Crohn's disease.

• Authors: Hadi Esmaily, Amanollah Vaziri-Bami, Amir Ebrahim Miroliaee, Maryam Baeeri, Mohammad Abdollahi
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 25 Issue 6 Pg. 723-33 (Dec 2011) ISSN: 1472-8206 [Electronic] England
• PMID: 21077947 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 The Authors Fundamental and Clinical Pharmacology. 2010 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Antioxidants
• Cholagogues and Choleretics
• NF-kappa B
• Silymarin
• Silybin
• Ursodeoxycholic Acid
• Dexamethasone
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Antioxidants (administration & dosage, metabolism, pharmacology)
• Cholagogues and Choleretics (administration & dosage, pharmacology)
• Colitis (drug therapy, pathology)
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Drug Therapy, Combination
• Male
• NF-kappa B (antagonists & inhibitors)
• Rats
• Rats, Wistar
• Silybin
• Silymarin (administration & dosage, pharmacology)
• Trinitrobenzenesulfonic Acid (toxicity)
• Ursodeoxycholic Acid (administration & dosage, pharmacology)