The protective effects of betanin against experimental gastric ulcer by reduction of ROS and suppression of inflammatory genes via NF-κB, iNOS, COX-2 and TNF-α pathways

Abstract

Betanin, a prominent compound found in beetroot, however, the potential protective effects of this compound against gastric damage and ulceration have yet to be explored. This study aims to investigate the impact of purified beetroot betanin (Bet) on the activities of inflammatory enzymes and gene expressions associated with inflammation in gastric tissues. Gastric ulcer rats were induced by ethanol at dose 5ml/kg body weight. Ulcerated rats were treated by purified betanin or omeprazole; from which some inflammation-related genes and gastric-inflammation enzymes were investigated using RT-PCR and biochemical analysis, respectively. Bet effectively suppressed the activities of key enzymes involved in gastric mucosal inflammation, including 5-Lipoxygenase (5-LO), Hyaluronidase (HAase), and myeloperoxidase (MPO), by 58%, 50%, and 45%, respectively. Docking studies showed Bet binding to catalytic sites or key regions for enzymes’ activities, thus explaining the inhibitory capacity. Bet ingestion decreased the expression levels of inflammation-related genes, factor-kappa B (NF-ϰB) by 57%. This down-regulation subsequently led to a reduction in the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α). Bet ingestion supressed thiobarbituric acid reactive substance (TBARS) rates by 59%, augmented nitric oxide (NO) level by 107% and protected gastric tissues from damage and ulceration. Bet revealed gastro-protective effects as confirmed by a reduction in the ulceration surface area and the acidity by 75.9% and 40%, respectively, and a significant increase in the weight of mucus and the curative index by 117% and 74.5%, respectively. In conclusion, these outcomes of physiological and molecular-based investigations are indicative of potential use of Bet as a functional food additive for the prevention of gastric ulcer.