South African marine algae are a prevalent traditional medicine utilized by indigenous populations. There has been recent attention on the health advantages of South African marine algae and its bioactive compounds, which have been associated with favourable health outcomes such as diabetes and obesity. This study investigated the antioxidant, anti-obesogenic and anti-diabetic potentials of three South African marine algal species or seaweeds, namely Codium fragile, Radicilingua thysanorhizans and Mazzaella capensis using a variety of in vitro and in silico experiments. The crude extracts, obtained using different solvents (aqueous and ethanol), were examined to assess their total phenolic and total flavonoid content as well as their antioxidant properties by means of 2,2-diphenyl-β-picrylhydrazyl (DPPH), non-site-specific hydroxyl radical (OH•), and nitric oxide (NO) radical scavenging assays. Thereafter, the extracts were subjected to carbohydrate digestive enzyme inhibitory assays, including α-glucosidase and α-amylase, and a lipid digestive enzyme inhibitory assay, such as pancreatic lipase. The glucose uptake by yeast cells was also evaluated in vitro. The subjection of the marine algal extracts to LC-MS analysis revealed several beneficial compounds. These compounds were further docked against α-glucosidase and α-amylase, and a lipid digestive enzyme, pancreatic lipase. The results of this study indicate that the selected South African marine algae possess potent antioxidant capacity while also exhibiting anti-obesogenic and anti-diabetic activities by inhibiting carbohydrate and lipid digesting enzyme activity as well as by increasing glucose uptake in yeast cells. Evaluated ADME profiles revealed that the compounds of these plants have excellent bioavailability and are considered safe for consumption. Overall, the results of this study suggest that all studied seaweeds have potential antioxidant, anti-diabetic, and anti-obesogenic potentials with Codium fragile found to be the most promising among them. The current work serves as a validation of the data currently available regarding the antioxidant, anti-obesogenic and anti-diabetic potential of C. fragile. The study will also serve as a first-report of the aforementioned activities for R. thysanorhizans and M. capensis.
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