Nyctanthes arbor-tristis leaf extract ameliorates hyperlipidemia- and hyperglycemia-associated nephrotoxicity by improving anti-oxidant and anti-inflammatory status in high-fat diet-streptozotocin-induced diabetic rats.

Type 2 diabetes is a multifactorial disorder coupled with impaired glucose tolerance, diminished insulin sensitivity and hyperlipidemia. Incessant hyperglycemia and hyperlipidemia led a towering risk to develop cardiovascular hitches with end-stage renal failure. Leaves of Nyctanthes arbor-tristis L. (NAT) (family: Oleaceae) is traditionally used by tribes of Assam for various ailments without proper scientific validation and appropriate mechanism of action for its activity. Hence, we aimed to evaluate the mechanism involved in the hypoglycemic and hypolipidemic effects of NAT leaves in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were fed with in-house prepared high-fat diet (HFD) for a period of 4 weeks to create insulin resistance. Streptozotocin was injected intraperitoneally to these rats to cause ß-cell destructions to create a model of type 2 diabetes. Our results have shown that NAT extract has a dose-dependent hypoglycemic and hypolipidemic activity in controlling the early biochemical parameters of kidney and lipids. Moreover, the extract has anti-oxidant and anti-inflammatory activities which were more pronounced at a dose of 400 mg/kg body weight. NAT treatment group also restored the normal architecture of the kidney and aorta tissue. GC-MS data analysis revealed the presence of several active compounds which are directly or indirectly responsible for its anti-diabetic and anti-hyperlipidemic activity. The apparent mechanism of NAT for its nephroprotection may be due to the suppression of hyperglycemia-mediated oxidative stress and amelioration of inflammatory cascades allied with NF-kB activation.

Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy.

Hyperglycaemia-mediated oxidative stress plays an imperative role in the progression of diabetic nephropathy. NF-kB is an important transcription factor in eukaryotes which regulates a diverse array of cellular process, including inflammation, immunological response, apoptosis, growth and development. Increased expression of NF-kB plays a vital role in the pathogenesis of many inflammatory diseases including diabetic nephropathy. Hence, the present study was designed to explore the nephroprotective nature of diosmin by assessing the various biochemical parameters, markers of oxidative stress and proinflammatory cytokine levels in alloxan-induced diabetic Wistar rats. Type 2 diabetes was induced in Wistar rats by single intraperitoneal injection of alloxan (120 mg/kg body weight). Seventy-two hours after the conformation of diabetes (blood glucose level ≥ 250 mg/dl), the rats were segregated into four groups, each group having six animals. Diabetic rats were treated with diosmin at a dose of 50 mg and 100 mg/kg body weight respectively. After the 28th day of treatment, rats were sacrificed, blood serum, plasma and kidney tissue were collected for various biochemical analysis. Inflammatory cytokine levels were measured through ELISA kit. Diosmin treatment produces significant reduction in the blood glucose and plasma insulin level and increases the body weight when compared with diabetic rats. Elevated level of malondialdehyde (MDA) and decrease levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and nitric oxide (NO) were significantly restored after 28 days of diosmin treatment. Diosmin treatment group also restores the normal architecture of the kidney tissue which was confirmed by histopathological examination. Moreover, oral administration of diosmin shows a significant normalization in the level of NF-kB, proving its pivotal role in maintaining renal function. The above ameliorative effects were more pronounced with diosmin at a dose of 100 mg/kg body weight. The above results permit us to conclude that treatment with diosmin halts hyperglycaemia-mediated oxidative stress and decline in pro-inflammatory cytokines and thus has beneficial anti-diabetic activity.