Coloprotective effects of chebulic myrobalan extract by regulation of AMPK-SIRT1 signaling: A pharmacological and histopathological evaluation

Abstract

Ulcerative colitis is a chronic, refractory disease caused by dysregulation of mucosal immune responses to the indigenous bacterial flora as well as genetic and environmental variables. Recently, there has been increasing interest towards the use of herbal medicines for the treatment of ulcerative colitis and the potential benefits could lie in their high patient acceptability, effectiveness, safety, and relatively low cost. It has been reported that Chebulic myrobalan (Terminalia chebula) exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. The present study was designed to evaluate the protective potential of extract of dried fruit pulp of T. chebula against Dextran sulphate sodium (DSS)-induced ulcerative colitis in male BALB/c mice. Three cycles of DSS (3 % w/v in drinking water), each followed by a seven-day remission phase were used to induce ulcerative colitis in mice. Animals were treated with T. chebula (300 mg/kg and 600 mg/kg) starting from I^st remission period to the end of the study. Different biochemical assays, histological evaluation and molecular analysis were performed to evaluate the protective effects of T. chebula extract in DSS induced colitis. T. chebula modulates the expression of nuclear factor kappa B, adenosine monophosphate kinase, tumour necrosis factor-alpha, sirtuin 1 and interleukin-1β. Furthermore, it also accorded coloprotective effects against DNA damage, apoptosis, inflammation and nitrosative stress. Finally, it was found that the high dose of the T. chebula extract (600 mg/kg) was found to be more effective than a low dose (300 mg/kg) in restoring the ulcerative colitis induced colonic damage.