Senna petersiana (Bolle) leaf extract modulates glycemic homeostasis and improves dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats

Ethnopharmacological relevance: Senna petersiana (Bolle) is a native South African medicinal shrub combined locally with other plant products to manage diabetes or used as a single therapy for several other ailing conditions. Aim of the study: This study evaluated the antidiabetic and antilipidemic effects of S. petersiana leaf ethanol extract and its modulatory effects on dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats. Materials and methods: Six groups of 6-weeks old male Sprague Dawley rats were used in this study. Diabetes was induced in four of the groups by injecting (i.p.) 40 mg/kg of streptozotocin after a two-weeks feeding of 10% fructose via drinking water, while animals in the two normal groups were given similar volume of vehicle buffer and normal drinking water, respectively. After the confirmation of diabetes, treatment with 150 and 300 mg/kg body weight of the ethanolic leaf extract of S. petersiana proceeded for a period of 6 weeks. Results: Oral administration of S. petersiana leaf extract significantly lowered blood glucose, food and liquid intake, glycosylhaemoglobin in blood, liver and cardiac biomarkers, and lipid profile in serum and atherogenic index (AIP) in both the low and high-dose treated animal groups. This was accompanied by a simultaneous increase in Homeostatic Model Assessment-beta (HOMA-β) score, serum high-density lipoproteins cholesterol (HDL-c), and insulin levels. It also improved pancreatic and serum-reduced glutathione (GSH) levels, catalase, and superoxide dismutase (SOD) enzymes activities with a simultaneous reduction in malondialdehyde (MDA) and nitric oxide (NO) concentrations. Moreover, the extract modulated dysregulated α-amylase, lipase, cholinesterase, and 5′ nucleotidase enzyme activities in pancreatic tissue as well as glycogen metabolism in the liver. Analysis of the phytochemicals in the S. petersiana extract showed the presence of phytol, 4a,7,7,10a-tetramethyldodecahydrobenzo[f]-chromen-3-ol, phytol acetate, solasodine glucoside, cassine, veratramine and solasodine acetate. Amongst these compounds, solasodine glucoside had the best binding energy (ΔG) with the selected diabetes-linked enzymes via molecular docking simulation. Conclusion: Data from this study demonstrate the antidiabetic effects of S. petersiana leaf extract via the modulation of the dysregulated indices involved in type 2 diabetes and its associated complications. Although it has been shown safe in animals, further toxicological studies are required to ensure its safety for diabetes management in humans.