Antidiabetic effect of Dodonaea viscosa aerial parts in high fat diet and low dose streptozotocin-induced type 2 diabetic rats: a mechanistic approach.
BACKGROUND
High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model for type 2 diabetes mellitus (T2DM) that would closely reflect the natural history and metabolic characteristics of human T2DM and is also suitable for pharmacological screening.


OBJECTIVE
The present study was designed to investigate the effect of the water extract (DVW) and the polar fraction of ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on biochemical parameters in type 2 diabetes induced by a standardized HFD and low dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action we evaluated its effects on a battery of targets involved in glucose homeostasis (in vitro studies).


METHODS
Different doses of DVW and DVE-4 were administered once daily for two weeks to HFD + STZ diabetic rats. Quantification of biomarker quercetin was done using HPLC.


CONCLUSIONS
Both DVW and DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model assessment (HOMA), lipid profiles, and significantly improved glucose tolerance and HDL-c levels. In addition, the extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different, bioassays, DVW and DVE-4 showed inhibition of PTP-1B and at a concentration of 10 μg/mL showed 60 and 54.2% binding to PPARγ, respectively. Both extract/fraction exhibited stimulation of glucose uptake by skeletal muscles.


CONCLUSIONS
Taken together, these results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin resistance, lipid abnormalities and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.
Veerapur
V P
VP
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India.
Prabhakar
K R
KR
Kandadi
M R
MR
Srinivasan
K K
KK
Unnikrishnan
M K
MK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008517:Phytotherapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D029631:Sapindaceae / Q000737:chemistry*; D013311:Streptozocin
D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D013311:Streptozocin; D002784:Cholesterol; D011794:Quercetin