Antidiabetic and anti-obesogenic potential of some artificial sweeteners; and their modulatory effects on iron-induced hepatic oxidative stress

The excessive consumption of simple carbohydrates, such as sucrose and fructose, has been identified as one of the most significant risk factors contributing to the development of type 2 diabetes and obesity. Consequently, the use of artificial sweeteners (AS) as sugar alternatives has surged. Present study was intended to examine the antioxidant, anti-obesogenic, and anti-diabetic potential of commonly used AS, namely saccharin, sucralose, aspartame, and acesulfame potassium, using in vitro, ex vivo, and in silico experimental models. The in vitro antioxidant activity was determined using the DPPH, NO, and OH^• radical scavenging activities. The effects of the sweeteners on α-amylase, α-glucosidase, pancreatic lipase inhibitions, and glucose uptake using yeast cells were also evaluated. Computational molecular docking was further conducted to examine their mode of enzyme inhibitory activity. Additionally, their protective effect against Fe²⁺-induced oxidative hepatic injury was investigated ex vivo. Saccharin showed the most significant (p < 0.05) in vitro antioxidant activity among the other sweeteners. Sucralose showed the most potent inhibitory effects against carbohydrate digestive enzymes, α-amylase (IC₅₀= 0.2%), and α-glucosidase (IC₅₀= 0.60%). Furthermore, it exhibited the most pronounced enhancement of glucose uptake in yeast cells (IC₅₀= 0.06%). While aspartame was most effective against pancreatic lipase (p < 0.05), molecular docking results revealed that all sweeteners have appreciably strong binding affinity for the enzymes studied. Further, treatment with AS reversed oxidative stress, as evident by a reduction in nitric oxide (NO) and increased glutathione (GSH) level, catalase, and superoxide dismutase (SOD) activities, with saccharin being the most effective in terms of antioxidative effects. Overall, the results of this study suggest that all studied AS have some level of antioxidant, anti-diabetic, and anti-obesogenic effects with saccharin found to be the most beneficial sweetener followed by sucralose, at least in this experimental condition. Hence, it is recommended that saccharin and sucralose may be used as a supplement in antidiabetic and anti-obesity food products.