Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE-RAGE signalling.

Resveratrol (RSV) has been shown to ameliorate hyperglycaemia and hyperlipidaemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on diabetes mellitus (DM)-induced vasculopathy and explored its possible mechanism. Male Sprague-Dawley rats were injected with streptozotocin at 65 mg/kg body weight The induction of DM was confirmed by a fasting plasma glucose level > or = 300 mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75 mg/kg body weight three times a day for 4-8 weeks. Animals were sacrificed and vessel wall histology was examined by microscopy. The vascular smooth muscle cell activation was assessed by the medial thickness, collagen deposition, and the expressions receptor for advanced glycation end product, NF-kappaB, proliferation cell nuclear antigen, and the levels of Erk1/2 phosphorylation. In RSV-treated DM rats, the vascular wall thickening, collagen deposition/cross-linking, and vascular permeability were all alleviated compared with that of the untreated DM rats. The vascular smooth muscle cell of the RSV-treated rats was characterized with less proliferation, lower NF-kappaB, and Erk1/2 activation, decreased proliferation cell nuclear antigen and receptor for advanced glycation end product expression. Moreover, the plasma fructosamine was significantly reduced in RSV-treated DM rats. RSV alleviated DM-induced vasculopathy through attenuation of advanced glycation end product-receptor for advanced glycation end product-NF-kappaB signalling pathway.

Jing YH ，Chen KH ，Yang SH ，Kuo PC ，Chen JK ... -  《-》

Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats.

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte injuries of diabetic kidneys are lessened by RSV.

Chen KH ，Hung CC ，Hsu HH ，Jing YH ，Yang CW ，Chen JK ... -  《-》

Deposition of advanced glycation end products (AGE) and expression of the receptor for AGE in cardiovascular tissue of the diabetic rat.

Sun M ，Yokoyama M ，Ishiwata T ，Asano G ... -  《-》

Resveratrol ameliorates metabolic disorders and muscle wasting in streptozotocin-induced diabetic rats.

Chen KH ，Cheng ML ，Jing YH ，Chiu DT ，Shiao MS ，Chen JK ... -  《-》

The effects of resveratrol on cyclooxygenase-1 and -2, nuclear factor kappa beta, matrix metalloproteinase-9, and sirtuin 1 mRNA expression in hearts of streptozotocin-induced diabetic rats.

Yar AS ，Menevse S ，Alp E 《-》