Arjunarishta alleviates experimental colitis via suppressing proinflammatory cytokine expression, modulating gut microbiota and enhancing antioxidant effect.

Traditional ayurvedic medicine, Arjunarishta (AA) is used to treat several inflammatory conditions including dysentery associated with blood. The formulation is a decoction of Terminalia arjuna (Roxb.) Wight and Arn. (TA), Madhuca indica J.F.Gmel., Vitis vinifera L., Woodfordia fruticosa (L.) Kurz., and Saccharum officinarum L. Terminalia arjuna, a major constituent of this formulation has been recognized for anti-inflammatory effects. This study aimed at evaluating beneficial effects of AA and probable mechanism of action in Trinitrobenzenesulphonicacid (TNBS) induced colitis model. Response to AA treatment was explored through determination of disease activity index (DAI), histological assessment and damage scores, colonic pro-inflammatory cytokine/chemokine expression and estimation of oxidative stress biomarkers. Improvement in gut microbiome and plasma zinc level was also assessed. Study findings directed therapeutic effects of AA treatment in colitis model by attenuating the colitis symptoms such as weight loss, diarrhoea, blood in stool; histological damage; and downregulated expression of pro-inflammatory cytokines/chemokine (TNF-α, IL-1ß, IL-6) and MCP-1). Similarly reduced oxidative stress by decreased level of Nitric Oxide (NO), Myeloperoxidase (MPO), Malondialdehyde (MDA) and enhanced level of Catalase (CAT), Superoxide dismutase (SOD) and Reduced Glutathione (GSH) was also witnessed. In addition, an improved beneficial fecal microbiome profile and restored plasma zinc status was revealed compared to the TNBS control group. The present study directs that downregulated pro-inflammatory cytokines/chemokine expression, enhancement of antioxidant effect, increased plasma zinc status and promising role in modulating fecal microbiome might be potential mechanisms for the therapeutic effect of AA treatment against colitis.

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 anti-inflammatory, 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 (DAI); 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-1ß, TNF-α 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.