Ameliorative effects of combination therapy with metformin and crocin in experimental colitis in rats

Abstract

Background and purpose:Inflammatory bowel disease (IBD) is characterized by aberrant immune responses in the colon, leading to the inflammatory cascades. Metformin (MTF) and crocin demonstrated beneficial effects in reducing inflammation and oxidative stress, as the main triggers of IBD. Considering the coloprotective properties of MTF and crocin alone, the present study aims to investigate the possible therapeutic effects of combination therapy with MTF and crocin on the acetic acid-induced colitis model.Experimental approach:Acute colitis was induced in Wistar rats by intrarectal administration of acetic acid. Nine study groups were assessed, including normal group received normal saline, control group received normal saline after colitis induction, dexamethasone as reference (1 mg/kg), MTF-treated groups received 100, 150, 200 mg/kg of drug, crocin-treated received 20 and 30 mg/kg of crocin, and combination therapy received MTF (150 mg/kg) + crocin (20 mg/kg). Colon tissues were collected to assess macroscopic, microscopic, and biochemical parameters.Findings/Results:Our data revealed that the combination therapy, crocin-treated and MTF-treated (at the higher dose) groups, ameliorated disease severity by decreasing myeloperoxidase activity and malondialdehyde level, compared to the control group. Combination therapy was also effective in attenuating macroscopic parameters, including ulcer index as well as wet weight of the colon. Histopathological scores considerably decreased in all groups.Conclusion and implications:MTF, crocin, and their combined administration exerted ameliorative effects in the colons of acetic acid-induced colitis rats, which is probably due to their anti-inflammatory and antioxidant properties. Further experimental studies are required to elucidate the underlying mechanisms.