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1. Curcumin is a naturally occurring poly-phenolic compound with a broad range of favourable biological functions, including anti-cancer, anti-oxidant and anti-inflammatory activities. The low bioavailability and in vivo stability of curcumin require the development of suitable carrier vehicles to deliver the molecule in a sustained manner at therapeutic levels. 2. In the present study, we investigated the feasibility and potential of poly(caprolactone) (PCL) nanofibres as a delivery vehicle for curcumin for wound healing applications. By optimizing the electrospinning parameters, bead-free curcumin-loaded PCL nanofibres were developed. 3. The fibres showed sustained release of curcumin for 72 h and could be made to deliver a dose much lower than the reported cytotoxic concentration while remaining bioactive. Human foreskin fibroblast cells (HFF-1) showed more than 70% viability on curcumin-loaded nanofibres. 4. The anti-oxidant activity of curcumin-loaded nanofibres was demonstrated using an oxygen radical absorbance capacity (ORAC) assay and by the ability of the fibres to maintain the viability of HFF-1 cells under conditions of oxidative stress. 5. The curcumin-loaded nanofibres also reduced inflammatory induction, as evidenced by low levels of interleukin-6 release from mouse monocyte–macrophages seeded onto the fibres following stimulation by Escherichia coli-derived lipopolysaccharide. 6. The in vivo wound healing capability of the curcumin loaded PCL nanofibres was demonstrated by an increased rate of wound closure in a streptozotocin-induced diabetic mice model. 7. These results demonstrate that the curcumin-loaded PCL nanofibre matrix is bioactive and has potential as a wound dressing with anti-oxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

1. Oxidative stress contributes to endothelial dysfunction and atherogenesis in diabetes. The present study tested the hypothesis that a high-cholesterol diet accelerates endothelial dysfunction in Ins2Akita mice, a Type 1 diabetic model with a spontaneous autosomal preproinsulin gene ( Ins2 gene) mutation, through further increase of superoxide production. 2. The Ins2Akita diabetic mice were fed a high-cholesterol diet (1.25% cholesterol) for 4 months. Some Ins2Akita mice were also treated for 4 months with the selective NADPH oxidase inhibitor apocynin (4 mg/kg per day in drinking water). Oxidative stress markers, tetrahydrobiopterin (BH4) levels, GTP cyclohydrolase I activity and endothelial function were determined in serum or arteries afterwards. 3. Serum lipid peroxidation and arterial superoxide levels were increased, whereas arterial BH4 levels and GTP cyclohydrolase I activity were decreased, in Ins2Akita mice on a high-cholesterol diet, resulting in impaired endothelium-dependent nitric oxide-mediated relaxation in response to acetylcholine. 4. In vivo treatment with apocynin not only blunted serum lipid peroxidation and arterial superoxide levels, but also increased BH4 levels and GTP cyclohydrolase I activity, resulting in improved endothelium-dependent relaxation. 5. These results suggest that NADPH oxidase may play a potential role in oxidative stress-induced arterial BH4 and GTP cyclohydrolase I deficiency, resulting in endothelial dysfunction in Ins2Akita Type 1 diabetic mice fed a high-cholesterol diet. [ABSTRACT FROM AUTHOR]

1. Superoxide has been reported to be involved in vascular dysfunction in diabetes. The Ins2Akita mouse is an autosomal dominant mutant diabetic model that can serve as an excellent substitute for the Type 1 diabetic mouse model induced by chemical diabetogens. The purpose of the present study was to investigate the role of superoxide on vascular dysfunction using this new diabetic model. 2. Compared with age-matched normal C57BL/6 mice, in Ins2Akita diabetic mice arterial superoxide, lipid peroxidation production (1.2 ± 0.1 vs 17.4 ± 1.9 mmol/mg tissue, respectively; P < 0.01) and plasma lipid peroxidation production (0.08 ± 0.02 vs 0.40 ± 0.03 mmol/L, respectively; P < 0.01) were increased. Meanwhile, expression of vascular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 in the aorta and/or plasma was elevated. 3. The contraction of carotid arteries to U46619 in Ins2Akita diabetic mice was significantly enhanced compared with control mice ( P < 0.05). Tempol (a scavenger of superoxide), apocynin (an inhibitor of NADPH oxidase) and allopurinol (an inhibitor of xanthine oxidase) all not only decreased superoxide in carotid arteries, but also suppressed arterial contractions to U46619 in Ins2Akita diabetic mice. Indomethacin, an inhibitor of cyclo-oxygenase, and chelerythrine, an inhibitor of protein kinase C, also suppressed the enhanced vascular contraction. 4. These results suggest that increased arterial superoxide generated from diverse sources may potentiate the contractions of carotid arteries in Ins2Akita diabetic mice. [ABSTRACT FROM AUTHOR]

1. Tetrahydrobiopterin (BH4) is an essential cofactor that maintains the normal function of endothelial nitric oxide (NO) synthase. Restenosis is a key complication after transluminal angioplasty. Guanosine 5′-triphosphate-cyclohydrolase I (GTPCH) is the first rate-limiting enzyme for de novo BH4 synthesis. However, the role of GTPCH in restenosis is not fully understood. The present study tested the hypothesis that endothelial-targeted GTPCH overexpression retards neointimal formation, a hallmark of restenosis, in mouse carotid artery. 2. Transluminal wire injury was induced in the left carotid arteries of adult male wild-type C57BL/6 (WT) and endothelial GTPCH transgenic (Tg-GCH) mice. Re-endothelialization was confirmed with in vivo Evans blue staining. Endothelium-dependent and -independent relaxations were measured using isometric tension recording. Morphological analysis was performed 2 and 4 weeks after carotid injury to assess neointimal formation. Fluorescence-based high-performance liquid chromatography (HPLC) was used to determine GTPCH activity and BH4 levels. Basal NO release following carotid injury was assessed by N G-nitro-l-arginine methyl ester-induced vascular contraction. 3. The endothelium was completely removed upon transluminal wire injury and full re-endothelialization was achieved at Day 10. Endothelium-dependent relaxation was impaired 10 days and 4 weeks after carotid injury, whereas endothelium-independent relaxation remained unaffected. Morphological analysis revealed that the endothelial-specific overexpression of GTPCH reduced neointimal formation and medial hypertrophy 2 and 4 weeks after carotid injury. Both arterial GTPCH enzyme activity and BH4 levels were significantly elevated in Tg-GCH mice compared with WT mice and basal NO release of the injured carotid artery tended to increase in Tg-GCH mice. 4. These findings suggest that the endothelial overexpression of GTPCH increased endothelial BH4 synthesis and played a preventive role in neointimal formation induced by endothelium denudation. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to test the hypothesis that in vivo chronic inhibition of NAD(P)H oxidase reduces cerebrovascular fibronectin expression in stroke-prone renovascular hypertensive rats (RHRSP). 2. The RHRSP model was induced by two clips and NAD(P)H oxidase was inhibited with apocynin. The mRNA and protein expression of NAD(P)H oxidase subunit p22 phox in brains of RHRSP and Sprague-Dawley (control) rats was determined using real-time reverse transcription–polymerase chain reaction, western blot and immunohistochemistry. The expression of fibronectin protein was localized immunohistochemically in cerebral vessels and then quantified by western blot. 3. Cerebrovascular fibronectin levels in RHRSP ( n = 6) were significantly higher than control ( n = 5) levels 8 weeks after operation (1.29 ± 0.04 vs 1.15 ± 0.02, respectively; P = 0.007). The p22 phox immunopositive reactivity was localized in the cerebral vasculature of control rats and RHRSP. Furthermore, chronic treatment of RHRSP with apocynin, a selective NAD(P)H oxidase inhibitor, in the drinking water for 4 weeks (1.5 mmol/L, 5 weeks after operation) resulted in a significant decrease in the expression of p22 phox protein (0.85 ± 0.01 vs 0.93 ± 0.01 in non-treated RHRSP; n = 5; P = 0.002), with a concomitant reduction of fibronectin levels in the cerebral vasculature (1.31 ± 0.03 vs 1.56 ± 0.05 in non-treated RHRSP; n = 5; P = 0.002). No significant differences were detected in the expression of p22 phox mRNA and protein between RHRSP (4 and 8 weeks after renal artery constriction) and the control group. 4. These findings suggest that the chronic inhibition of NAD(P)H oxidase in vivo by apocynin reduces cerebrovascular fibronectin levels, which may lessen hypertensive cerebrovascular fibrosis. [ABSTRACT FROM AUTHOR]