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
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Submission date: 2016-05-31
Final revision date: 2016-07-29
Acceptance date: 2016-08-12
Online publication date: 2016-10-26
Publication date: 2018-08-07
Arch Med Sci 2018;14(5):1163–1172
Diabetes mellitus is characterized by hyperglycaemia causing changes in plasma lipoproteins, which leads to insulin resistance, secretion defects or both. 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- (TNF-), 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.

DMDD significantly increased the insulin level (all p < 0.05). In contrast, FBG, IL-6, TNF-, TC, TG and FFA were significantly decreased (all p < 0.05). However, DMDD induced the activation of adipocyte peroxisome proliferator-activated receptor  (PPAR-), confirmed by increased protein and mRNA expression of PPAR-

DMDD possessed hypoglycaemic activity due to its potential mechanism involving PPAR-mediated adipocyte endocrine regulation.