The progression of secondary complications in type 2 diabetes (T2D) has been linked to oxidative stress caused by hyperglycemia. Therefore, the control of hyperglycemia is the main target in the treatment of diabetes. The present study investigated the scavenging and ameliorative potentials of different fractions of Azadirachta indica (A. indica) ethanol stem bark extract in Fe²⁺-induced oxidative injury in hepatic tissue as well as their ability to inhibit enzymes linked to diabetes and in enhancing muscle glucose uptake via some in vitro and ex vivo experimental models. The results revealed that the butanol fraction of the extract showed a significantly (p < 0.05) higher DPPH scavenging activity than the other fractions (IC₅₀ 0.0154 μg/mL), while the aqueous fraction showed the highest FRAP activity (IC₅₀ 25.32 μg/mL). Although all the fractions ameliorated Fe²⁺-induced oxidative injury in hepatic tissue by significantly reducing malondialdehyde (MDA) concentration in a dose dependent manner, the butanol fraction showed the highest activity in this regard. In addition, the activities of catalase and superoxide dismutase (SOD) were significantly improved by the butanol and dichloromethane fractions. Butanol and ethyl acetate fractions showed the highest inhibitory effect on α-glucosidase (IC₅₀ 0.23 μg/mL) and α-amylase (IC₅₀ 14.79 μg/mL) activities, respectively. Although all the fractions significantly improved glucose uptake in psoas muscle with or without insulin, the butanol fraction showed the highest activity (GU₅₀ 6.22 μg/mL) in this regard. Gas chromatography-mass spectroscopy (GC-MS) analysis of the fractions revealed the presence of sistosterol, stigmasterol, campestrol, squalene, nimbiol among others. Molecular docking of some of these compounds with AMP-activated protein kinase (α-AMPK), α-amylase and α-glucosidase showed a positive interaction. These results suggest that the butanol and ethyl acetate fractions of A. indica may have bioactive compounds with antidiabetic potentials.

Chronic hyperglycemia has been implicated in the development of oxidative stress and as a major factor in etiology of secondary complication in diabetes. In the present study, the antidiabetic potential of Phragamenthra incana (P. incana) hot infusion and its possible inhibitory effects on carbohydrate digesting enzymes, promotion of muscle glucose uptake, and the antioxidative potentials in Fe²⁺-induced oxidative stress in hepatic tissue were investigated. The infusion significantly (p < 0.05) scavenged free radicals (DPPH) and displayed favourable ferric reducing antioxidant power (FRAP) with increasing concentrations. It also significantly ameliorated Fe²⁺-induced oxidative stress in hepatic tissues by increasing superoxide dismutase (SOD) and catalase activities and depleting malondialdehyde (MDA) level. The results further showed that the infusion significantly (p < 0.05) inhibited α-amylase and α-glucosidase activity, and enhanced muscle glucose uptake, with and without insulin. Liquid Chromatography-Mass Spectroscopy (LCMS) analysis of the infusion revealed the presence of 2-methoxythiazole; l-cysteine; nicotinic acid; S-methyl-l-cysteine; isoquinoline, 1-methyl-; and 1H-indole-2,3-dione,5-methyl. The results of this study suggest that the observed antidiabetic and antioxidative potentials of P. incana could be attributed to its identified phytochemical constituents, however, this supports folkloric medicinal use of this plant.