Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells.

Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions.

Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling.

Hyperglycemia-mediated oxidative stress plays a crucial role in the progression of diabetic nephropathy. Hence, the present study was hypothesized to explore the renoprotective nature of resveratrol by assessing markers of oxidative stress, proinflammatory cytokines and antioxidant competence in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol to diabetic rats showed a significant normalization on the levels of creatinine clearance, plasma adiponectin, C-peptide and renal superoxide anion, hydroxyl radical, nitric oxide, TNF-α, IL-1ß, IL-6 and NF-κB p65 subunit and activities of renal aspartate transaminase, alanine transaminase and alkaline phosphatase in comparison with diabetic rats. The altered activities of renal aldose reductase, sorbitol dehydrogenase and glyoxalase-I and elevated level of serum advanced glycation end products in diabetic rats were also reverted back to near normalcy. Further, resveratrol treatment revealed a significant improvement in superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities and vitamins C and E, and reduced glutathione levels, with a significant decline in lipid peroxides, hydroperoxides and protein carbonyls levels in diabetic kidneys. Similarly, mRNA and protein analyses substantiated that resveratrol treatment notably normalizes the renal expression of Nrf2/Keap1and its downstream regulatory proteins in the diabetic group of rats. Histological and ultrastructural observations also evidenced that resveratrol effectively protects the kidneys from hyperglycemia-mediated oxidative damage. These findings demonstrated the renoprotective nature of resveratrol by attenuating markers of oxidative stress in renal tissues of diabetic rats.

Wound healing properties of Indian propolis studied on excision wound-induced rats.

CONTEXT: In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. OBJECTIVE: The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. MATERIALS AND METHODS: Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. RESULTS: Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. DISCUSSION AND CONCLUSION: It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.

Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide-induced experimental diabetic rats.

The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin-nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-alpha, IL-1 beta, IL-6, NF-kappaB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.

Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats.

Chronic exposure of pancreatic beta-cells to supraphysiologic glucose causes adverse beta-cell dysfunction. Thus, the present study was aimed to investigate the hypothesis that oral administration of resveratrol attenuates hyperglycemia, proinflammatory cytokines and antioxidant competence and protects beta-cell ultrastructure in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 unit and nitric oxide (NO) with concomitant elevation in plasma insulin. Further, resveratrol treated diabetic rats elicited a notable attenuation in the levels of lipid peroxides, hydroperoxides and protein carbonyls in both plasma and pancreatic tissues. The diminished activities of pancreatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) as well as the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were reverted to near normalcy by resveratrol administration. Based on histological and ultrastructural observations, it is first-time reported that the oral administration of resveratrol may effectively rescue beta-cells from oxidative damage without affecting their function and structural integrity. The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic beta-cells of diabetic rats.

Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats.

Resveratrol, a ubiquitous stress-induced phytoalexin, has demonstrated a wide variety of biological activities which make it a good candidate for the treatment of diabetes mellitus. The present study was aimed to evaluate its therapeutic potential by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. The daily oral treatment of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days demonstrated a significant (p<0.05) decline in blood glucose and glycosylated hemoglobin levels and a significant (p<0.05) increase in plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver and kidney tissues of diabetic rats were significantly (p<0.05) reverted to near normal levels by the administration of resveratrol. Further, resveratrol administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of resveratrol in diabetic rats. The obtained results were compared with glyclazide, a standard oral hypoglycemic drug. Thus, the modulatory effects of resveratrol on attenuating these enzymes activities afford a promise for widespread use for treatment of diabetes in the future.

Resveratrol, a natural phytoalexin, normalizes hyperglycemia in streptozotocin-nicotinamide induced experimental diabetic rats.

Resveratrol is a polyphenolic phytoalexin produced in appreciable amounts as a secondary metabolite in grapevines in response to fungal infections. Based on the present knowledge, it appears to be a promising bioactive natural molecule with potential applications in phytotherapy or pharmacology. The present study was aimed to evaluate the antidiabetic properties of resveratrol in streptozotocin-nicotinamide induced experimental diabetes in rats. The diabetic rats orally treated with resveratrol (5 mg kg(-)(1)b.w d(-)(1)) for 30 days resulted in significant (p<0.05) decrease in the levels of blood glucose, glycosylated hemoglobin, blood urea, serum uric acid, serum creatinine and diminished activities of pathophysiological enzymes such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). The antihyperglycemic nature of resveratrol is also evidenced from the improvement in the levels of plasma insulin and hemoglobin. Further, the results are comparable with glyclazide, an oral standard drug. Thus, the present findings suggest that resveratrol may be considered as an effective therapeutic agent for the treatment of diabetes mellitus.