Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression

SIMPLE SUMMARY: A considerable number of diabetic patients are in favour of using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. Artemisia judaica (AJ) is one of the herbs documented to have antidiabetic effects. This study examined the effect of using combination of A. judaica extract (AJE) and the oral hypoglycemic drug glyburide (GLB, 5 mg/kg) on diabetic rats. Fasting blood glucose (FBG), insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and oxidative stress biomarkers were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of peroxisome proliferator-activated receptor α (PPAR-α) and nuclear factor erythroid 2-related factor-2 (Nrf2) genes was performed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Combination of GLB and 500 mg/kg of AJE highly improved FBG, insulin levels, HbA1c, and lipid profile in blood when compared with GLB monotherapy. Furthermore, GLB plus 500 mg/kg of AJE combination was the most successful in restoring insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets, restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that GLB plus 500 mg/kg of AJE combination gives greater glycemic improvement than GLB monotherapy. ABSTRACT: Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.