Molecular Mechanisms of Hypoglycemic and Antioxidative Effects of Phyllanthus Amarus on Streptozotocin-Induced Diabetic Rats

Abstract

bstract In the present study, we investigated the biochemical alterations and gene expression of carbohydrate and lipid metabolism after oral administration of Phyllanthus amarus. The quantitative estimation of total phenols, tannins and flavonoids showed that the extracts are rich in these compounds antioxidant potential of the ethanolic extract of the stem leaves of Phyllanthus amarus Schumach. & Thonn. Was evaluated by using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. The extract showed significant activities in all antioxidant assays compared to the reference antioxidant ascorbic acid in a dose dependent manner. Phyllanthus amarus significantly reduced the blood glucose level starting on the second week. Furthermore, the extract of P amarus showed significant increase in plasma insulin and tissue glycogen contents. The antidyslipidemic effect was demonstrated by a significant reduction in plasma total cholesterol (TC), triglycerides (TG), and low density lipoprotein-cholesterol (LDL-C), while the cardio-protective lipid, high density lipoprotein-cholesterol (HDL-C), was increased. Phyllanthus amarus also modulated the activities of carbohydrate-metabolizing enzymes by significantly increasing the activity of hexokinase and pyruvate kinase (p<0.05) and significantly reducing the activity of glucose-6-phosphatase, fructose-1,6-diphosphatase and glycogen phosphorylase (p<0.05). Phyllanthus amarus administration up-regulated mrna expression of Glucose Transporter-2 (GLUT-2), and increased lipolysis and cholesterol metabolism through up-regulation of lipoprotein lipase (LPL), Sterol Responsible Element Binding Protein-1a (STREBP-1a) expression. FAS expression was down regulated. The Phyllanthus amarus induced increase in serum insulin level, glucokinase (GK), aldolase, pyruvate kinase (PK), succinate dehydrogenase (SDH), and glycogen synthase activities in addition to a higher expression of insulin receptor A (IRA), GK, SDH. Keywords: P. amarus; Diabetes II; Gene expression ; Gene regulation ; Insulin ; Carbohydrate metabolic enzymes; lipid metabolism