Archives of Medical Science (Oct 2016)
Hypoglycaemic activity of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione in streptozotocin-induced diabetic mice through ameliorating metabolic function and regulating peroxisome proliferator-activated receptor γ
Abstract
Introduction: Diabetes mellitus is characterized by hyperglycaemia causing changes in plasma lipoproteins, which leads to insulin resistance, secretion defects or both. The dried Averrhoa carambola L. (Oxalidaceae) root known as yang tao gen (YTG) in Chinese materia medica has been used in traditional medicine for treating diabetes mellitus. The present study aimed to evaluate the ability of 2-dodecyl-6-methoxy-cyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. roots to lower hyperglycaemia and to investigate its potential mechanism in diabetic mice. Material and methods : DMDD was isolated using a column chromatographic technique. Experimental mice were fed with a high-fat diet for a month and were intravenously injected with streptozotocin (80 mg/kg, single dose). Diabetic mice were orally administered DMDD (12.5, 25, 50 mg/kg) and 50 mg/kg pioglitazone for 15 days. Fasting blood glucose (FBG), fasting blood insulin (FINS), pancreatic insulin content, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), as well as serum total cholesterol (TC), triglyceride (TG) and free fatty acid (FFA) were determined. Adipose tissue was assessed by histological examination, immunohistochemistry, western blot and reverse transcription-polymerase chain reaction methods. Results : DMDD significantly increased the insulin level. In contrast, FBG, IL-6, TNF-α, TC, TG and FFA were significantly decreased. However, DMDD induced the activation of adipocyte peroxisome proliferator-activated receptor γ (PPAR-γ), confirmed by increased protein and mRNA expression of PPAR-γ. Conclusions : DMDD possessed hypoglycaemic activity due to its potential mechanism involving PPAR-mediated adipocyte endocrine regulation.
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