Modulatory effects of extract of Heinsia crinita against fructose/streptozotocin-induced oxidative stress in diabetic rat models

Abstract

Oxidative stress plays a crucial role in the development of type 2 diabetes and the associated microvascular and cardiovascular complications. In the study, we have investigated the effects of Heinsia crinita (H. crinita) extracts on lipid peroxidation and oxidative stress responses using diabetic rats. Type 2 diabetes was induced with 10 % fructose/40 mg/kg body weight streptozotocin (STZ). H. crinita extract was administered at 200 and 400 mg/kg body weight twice daily for 21 days, in addition to metformin (MET: 500 mg/kg body weight) control. Molecular docking analysis was performed to determine the binding affinity of H. crinita extracts to the DNA binding domains of peroxisome proliferator-activated receptor (Ppar) and retinoid x receptor (Rxr) protein crystal structures, showing different binding affinities for putative active compounds from the plant. Fasting blood glucose (FBG), body and organ weight changes were determined showing that H. crinita extract induced an anti-hyperglycemic effect in the treated animals, with changes (either decrease or increase) in liver and kidney weights. A decrease in mRNA expression of peroxisome proliferator-activated receptors (ppar), sterol regulatory element-binding protein 1 (srebp-1c), liver x-receptor (lxr), retinoid x receptors (rxr), cytochrome p45041 (cyp4a1) and acyl-CoA oxidase (acox1) in diabetic animals were observed, compared to the control. A dose-specific decrease or increase in antioxidant enzymes (superoxide dismutase: SOD, catalase: CAT, reduced glutathione: GSH, glutathione peroxidase: GPx) transcripts and activity levels were also observed. We also observed exposure-specific decrease or increase of malondialdehyde (MDA) levels. Our data suggested that H. crinita extract possesses protective effects against diabetes-induced oxidative stress. These effects might be attributed to their binding and activation of nuclear receptors, indicating their cellular mode of action that is comparable to MET.