Table 1.
Effect of different treatments on body weight, as well as food and water intake in n-STZ diabetic rats.
Table 2.
Effect of different treatments on oral glucose tolerance test (OGTT) in n-STZ diabetic rats.
Fig 1.
Effect of different treatments on oral glucose tolerance test (OGTT) in n-STZ diabetic rats.
[A] Line curves depict the changes in blood glucose response in normal control, diabetic control, and diabetic treated groups [Galan 5 mg/kg; Vilda 30 mg/kg; or their combination, after 0, 30, 60, 90 and 120 min following administration of glucose (2.5 g/kg, p.o)]. All treatments were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M. [B] Area under the curve (AUC) of the OGTT to compare between different studied groups. As compared with normal control (*), diabetic control (#), Galan5 (η), and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05.
Fig 2.
Effect of galantamine and/or vildagliptin on glucose homeostasis.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on the fasting serum glucose (A), fructosamine (B), insulin (C), HOMA-IR (D), % β-cell function (E) in n5-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive and (b) synergistic interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 3.
Effect of galantamine and/or vildagliptin on serum lipid profile.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on the serum triglycerides (A), total cholesterol (B), free fatty acids (FFAs) (C), LDL-C (D), and HDL-C (E) in n5-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 4.
Effect of galantamine and/or vildagliptin on hepatic lipid profile.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on the hepatic triglycerides (A), total cholesterol (B), free fatty acids (FFAs) (C), as well as serum activities of AST (D), and ALT (E) in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda 30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 5.
Effect of galantamine and/or vildagliptin on muscular lipid profile.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on the muscular triglycerides (A), total cholesterol (B), and free fatty acids (FFAs) (C), in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 6.
Effect of galantamine and/or vildagliptin on AChE activity.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on the acetylcholinesterase (AChE) activity in brain (A), liver (B) and muscle (C) in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (b) Synergistic and (c) potentiating interaction when Galan 5 and Vilda 30 were combined using Factorial Design.
Fig 7.
Effect of galantamine and/or vildagliptin on oxidative stress parameters.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on hepatic (A) and muscular (B) transcription activation of Nrf2 (nuclear factor-erythroid-2-related factor 2), total antioxidant capacity (C, D) and malondialdehyde (MDA) content (E, F), respectively, in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive and (b) synergistic interactions when Galan5 and Vilda30 were combined using Factorial Design.
Fig 8.
Effect of galantamine and/or vildagliptin on apoptosis biomarkers.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan 5 + Vilda 30) on hepatic and muscular levels of caspase-3 (A, B) and cytochrome c (C, D), respectively, in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P < 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 9.
Effect of galantamine and/or vildagliptin on inflammatory mediators and adipokines.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan5 + Vilda 30) on serum TNF-α (A), visfatin (B) and adiponectin (C), as well as hepatic (D) and muscular (E) nuclear factor κB (NF-κB) in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 10.
Effect of galantamine and/or vildagliptin on insulin signaling pathway.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan5 + Vilda 30) on hepatic and muscular contents of phosphorylated insulin receptor (A, B), and p-Akt (C, D), respectively, as well as hepatic GLUT2 (E) and muscular GLUT4 (F) in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive interaction when Galan5 and Vilda30 were combined using Factorial Design.
Fig 11.
Effect of galantamine and/or vildagliptin on GLUT4 gene expression.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan5 + Vilda 30) on muscular GLUT4 gene expression in n-STZ diabetic rats. The upper panel represents stained agarose gels of RT-PCR products as a representative of one rat for each group. Data in the lower panel represents means of 10 rats ± S.EM as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05.
Fig 12.
Effect of galantamine and/or vildagliptin on Wnt/β-catenin pathway.
Effect of different doses of galantamine (Galan 2.5, 5 & 10 mg/kg), vildagliptin (Vilda 3, 10 & 30 mg/kg) and their combination (Galan5 + Vilda 30) on the hepatic and muscular contents of p-GSK-3β (A, B) and β-catenin (C, D) in n-STZ diabetic rats. Drugs were gavaged orally for four weeks. Values are means of 10 rats ± S.E.M as compared with normal control (*), diabetic control (#), Galan5 (η), Galan10 (ɸ) and Vilda30 (Ψ)-treated groups (one-way ANOVA followed by Tukey post hoc test) at P< 0.05. (a) Additive and (b) synergistic interactions when Galan5 and Vilda30 were combined using Factorial Design.
Table 3.
Correlation between HOMA-IR with acetylcholinesterase (AChE) activity, Nrf2 transcription activity, NF-κB, p-GSK-3β, and β-catenin.