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Brain glucose uptake is usually reduced in type 2 diabetes owing to downregulation of brain glucose transporters. The ability of Vernonia amygdalina to stimulate glucose uptake as well as ameliorate glucose-induced oxidative stress and proinflammation were investigated in rat brain. Hot infusion of V. amygdalina leaves was incubated with rat brain tissues for 2 h in the presence of glucose. Another incubation with glucose only, served as negative control while metformin served as positive control. Incubation of brain tissues with V. amygdalina led to significant (p < 0.05) increase in glucose uptake, reduced glutathione, nitric oxide and non-thiol proteins levels, superoxide dismutase, catalase and ATPase activities, while concomitantly decrease in myeloperoxidase activity and malondialdehyde level compared to the negative control. Incubation with glucose only, led to the development of nitrate, amide II and amide I functional groups which were removed on incubation with the infusion. LC-MS analysis revealed depletion of oxidative stress-induced 2-keto-glutaramic acid and cysteinyl-tyrosine metabolites in brain tissues, with concomitant generation of S-formylglutathione and adenosine tetraphosphate by the infusion. Pathway analysis of the metabolites revealed an activation of pyruvate metabolism pathway in the negative control, with the infusion reducing the intensity fold. LC-MS analysis of the infusion revealed the presence of l-serine, l-cysteine, l-proline, nicotinic acid, cumidine, salicylic acid, isoquinoline, 3-methyl-, and γ-octalactone. Except for l-serine, l-cysteine and l-proline, the other compounds were predicted to be permeable across the blood brain barrier. These results indicate the brain glucose uptake stimulatory and neuroprotective effect of V. amygdalina.

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 Fe 2+ -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 (IC 50 0.0154 μg/mL), while the aqueous fraction showed the highest FRAP activity (IC 50 25.32 μg/mL). Although all the fractions ameliorated Fe 2+ -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 (IC 50 0.23 μg/mL) and α-amylase (IC 50 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 (GU 50 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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

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 Fe 2+ -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 Fe 2+ -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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The antioxidative and antidiabetic effects and toxicity of caffeine-rich infusion of Cola nitida were investigated using in vitro, ex vivo and in silico models. C. nitida was infused in boiling water and allowed to cool before concentrating at <50°C. HPLC analysis of the infusion revealed a caffeine content of 80.08%. The infusion showed potent in vitro antioxidant activity by significantly (p<0.05) scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH). It significantly (p<0.05) inhibited α-glucosidase and α-amylase activities. Treatment of Fe 2+ induced oxidative hepatic tissues with the infusion led to increase Superoxide Dismutase (SOD) and catalase activities, and glutathione (GSH) level as well as decreased malondialdehyde (MDA) level. FTIR spectroscopy of hepatic metabolite revealed restoration of oxidative-induced depleted functional groups by the infusion. LC-MS analysis of the metabolite also revealed restoration of most depleted metabolites with concomitant generation of 4-O-Methylgallic, (-)-Epicatechin sulfate, L-Arginine, L-tyrosine, Citric acid and Decanoic acid in infusion-treated tissues. Pathway analysis of the identified metabolites revealed the presence of 21 metabolic pathways involved in normal hepatic tissues, 12 in oxidative injured tissues and 17 in the treated tissues. Treatment with the infusion restored 4 metabolic pathways common to the normal tissue and further activated 4 additional pathways. Prediction of oral toxicity of caffeine showed it to belong to class 3, with a LD 50 of 127mg/kg. Its toxicity target was predicted as Adenosine Receptor A2a. It was also predicted to be an inhibitor of CYP1A2. These results suggest the antioxidative and antidiabetic properties of C. nitida infusion, with caffeine as the major constituent., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The leaves of Dacryodes edulis were investigated for their anti-oxidative and anti-diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and aqueous) of the leaves were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phospatase activities. Their antioxidant and anti-apoptotic effects on Fe 2+ - induced oxidative injuries in pancreatic and hepatic tissues were also investigated ex vivo. The ethanol extract was subjected to Gas chromatography mass spectroscopy (GC-MS) and Fourier transform infrared (FTIR) spectroscopic analysis to identify its bioactive chemical constituents. The extracts showed potent free radical scavenging activity and significantly (p<0.05) inhibited all studied enzymes, with the ethanol extract showing greater activities. Superoxide Dismutase (SOD) and Catalase (CAT) activities were significantly (p<0.05) increased in both pancreatic and hepatic tissues with concomitant elevation of reduced glutathione (GSH) levels as well as reduced levels of malondialdehyde (MDA). The extracts significantly inhibited DNA fragmentation. These activities were dose - dependent. Amongst compounds identified, only Kaur-15-ene, Urs-12-ene-3-ol acetate and 2,3,23-trihydroxyolean-12-en-28-oic acid methyl ester showed strong binding affinities when docked with α-glucosidase (PDB ID:3TON). These results indicate the anti-oxidative, anti-diabetic and anti-obesogenic potentials of D. edulis leaves, which gives credence to its antidiabetic folkloric claims., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)