Beneficial role of Terminalia arjuna hydro-alcoholic extract in colitis and its possible mechanism

Ethnopharmacological relevance: Terminalia arjuna Roxb. (Combretaceae) is traditionally used in Ayurveda medicine and holds ethnomedicinal importance for treatment of gastrointestinal disorders. In view of its antiinflammatory, antidiarrheal and antioxidant potential, it could be beneficial for the treatment of inflammatory bowel disease (IBD), which is associated with interaction between genetic, environmental factors and intestinal microbiome leading to dysregulated immune responses. This study evaluates the effect of hydroalcoholic extract of Terminalia arjuna bark (TAHA) in trinitrobenzenesulfonic acid (TNBS) model of rat colitis which resembles human IBD. Materials and methods: TAHA (500, 250, 125 mg/kg) was administered orally for 28 days in TNBS induced rats. Response to treatment was assessed by comparing observations in diseased and treated groups using disease activity index (DAD; macroscopic/histological damage; determining oxidative stress indicators: myeloperoxidase, malondialdehyde, nitric oxide, catalase, superoxide dismutase, and reduced glutathione; gene expression of pro-inflammatory cytokines such as IL-6, IL-1D, TNF-alpha and chemokine: MCP-1. Furthermore, the role of TAHA in altering the gut microbiota profile in rat feces and plasma zinc was also studied. Results: TAHA treatment in colitic rats directed decreased DAI scores, macroscopic and histologic damage. It also reduced myeloperoxidase, malondialdehyde and nitric oxide level. Whereas, prevented depletion of plasma catalase, superoxide dismutase and glutathione level. In addition, TAHA treatment down-regulated the gene expression of pro-inflammatory mediators and displayed altered beneficial effect on fecal microbiota. Furthermore, enhanced plasma zinc level supported the beneficial effect of TAHA in colitic rats. The dose of TAHA that produced most significant beneficial effect was 500 mg/kg. Conclusion: TAHA administration relieved the disease activity in TNBS induced colitis by reducing expression of pro-inflammatory cytokines and chemokine, decreasing oxidative stress, and improving plasma zinc level and structure of gut microbiota.