Oral administration of green tea Epigallocatechin-3-gallate reduces oxidative stress and enhances restoration of cardiac function in diabetic rats receiving autologous transplantation of adipose-derived stem cells.

BACKGROUND: Cardio-dysfunction is one of the complications in patients with diabetes mellitus (DM). This paper aimed to investigate if oral administration of green tea Epigallocatechin-3-gallate (EGCG, E) and transplantation of adipose-derived stem cells (ADSC) show cross effects on the treatment of cardiomyopathy in rats with type 1 DM. MATERIALS AND METHODS: Wistar male rats were divided into four groups (each group contained 8 animals) including sham, DM (diabetic group), DM + ADSC (DM group with ADSC treatment) and DM + ADSC + E (DM + ADSC group with oral administration of EGCG). RESULTS: Pathological parameters including hypertrophy, inflammation, and fibrosis were activated in DM group. By contrast, all parameters were significantly improved in treatment group (DM + ADSC group). In addition, improvement of pathological parameters in DM + ADSC + E was significantly better than DM + ADSC. CONCLUSION: We found that EGCG can increase expression of survival marker in ADSC under high glucose environment and reduce serum oxidative stress in DM rats.

Green tea epigallocatechin gallate enhances cardiac function restoration through survival signaling expression in diabetes mellitus rats with autologous adipose tissue-derived stem cells.

The present study tests a hypothesis that cardioprotective effects mediated by autologous adipose-derived stem cells (ADSC) in rats afflicted with insulin-dependent diabetes mellitus (IDDM) may be synergistically enhanced by oral treatment with green tea epigallocatechin gallate (EGCG). Wistar rats were divided into sham, DM, DM+ADSC (autologous transplanted 1 × 106 cells per rat), and DM+ADSC+E (E, green tea oral administration EGCG). Heart tissues were isolated from all rats, and investigations were performed after 2-mo treatment. In the sham, DM, and DM+ADSC groups, we found that DM induced cardiac dysfunction (sham and DM) and autologous ADSC transplantation could partially recover cardiac functions (DM and DM+ADSC) in DM rats. Compared with DM+ADSC, significant improvement in cardiac functions can be observed in DM+ADSC+E in echocardiographic data, histological observations, and even cellular protein expression. Oral green tea EGCG administration and autologous ADSC transplantation show synergistically beneficial effects on diabetic cardiac myopathy in DM rats.NEW & NOTEWORTHY Cardiomyopathy can be induced in rats with diabetes mellitus (DM). Heart function can be restored in DM rats with adipose-derived stem cell treatment. Oral epigallocatechin gallate (EGCG) administration synergistically enhances cardiac function in DM rats with stem cell treatment. The EGCG and stem cell treatment cross-effect occurs via survival protein expression.

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease.

BACKGROUND: Enhanced advanced glycation end products deposition within myocardial tissue may cause diastolic dysfunction. However, whether this is related to left ventricular hypertrophy or inappropriate left ventricular mass remains unclear. METHODS: We prospectively enrolled 139 subjects at risk for cardiovascular diseases. We used echocardiography for measurements of left ventricular mass and cardiac systolic and diastolic functional parameters. An advanced glycation end product reader was applied for measurements of skin autofluorescence values. Comparisons of left ventricular mass and echocardiographic parameters between the higher and lower skin autofluorescence groups were analyzed. RESULTS: Compared with the lower skin autofluorescence group, left ventricular mass index and the ratio of observed left ventricular mass/predicted left ventricular mass (oLVM/pLVM) was significantly higher in the higher skin autofluorescence group (61.22 ± 17.76 vs. 47.72 ± 11.62, P < 0.01, 1.62 ± 0.38 vs. 1.21 ± 0.21, P < 0.01). After adjustment for potential confounding factors, skin autofluorescence was an independent factor for left ventricular mass index (ß = 0.32, P < 0.01) and the ratio of oLVM/pLVM (ß = 0.41, P < 0.01). Skin autofluorescence ≥2.35 arbitrary unit predicted left ventricular hypertrophy at a sensitivity of 58.8%, and a specificity of 73.0% (P < 0.01). Skin autofluorescence ≥2.25 arbitrary unit predicted inappropriate left ventricular mass at a sensitivity of 71.1%, and a specificity of 83.9% (P < 0.01). Skin autofluorescence was positively correlated with E/E', an indicator for diastolic dysfunction (r = 0.21, P = 0.01). CONCLUSIONS: Skin autofluorescence is a useful tool for detecting left ventricular hypertrophy, inappropriate left ventricular mass and diastolic dysfunction.

Chemiluminescence analysis of antioxidant capacity for serum albumin isolated from healthy or uremic volunteers.

Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end-stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD-ALB) or healthy volunteers (N-ALB). From high-performance liquid chromatography spectra, we observed that one uremic solute binds to HD-ALB via the formation of disulfide bonds between HD-ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N-ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD-ALB. Our results suggest that protein-bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD-ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd.

Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis.

BACKGROUND: Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. METHODS AND RESULTS: One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). CONCLUSIONS: Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.

Rapid method for the quantification of hydroquinone concentration: chemiluminescent analysis.

Topical hydroquinone serves as a skin whitener and is usually available in cosmetics or on prescription based on the hydroquinone concentration. Quantification of hydroquinone content therefore becomes an important issue in topical agents. High-performance liquid chromatography (HPLC) is the commonest method for determining hydroquinone content in topical agents, but this method is time-consuming and uses many solvents that can become an environmental issue. We report a rapid method for quantifying hydroquinone content by chemiluminescent analysis. Hydroquinone induces the production of hydrogen peroxide in the presence of basic compounds. Hydrogen peroxide induced by hydroquinone oxidized light-emitting materials such as lucigenin, resulted in the production of ultra-weak chemiluminescence that was detected by a chemiluminescence analyzer. The intensity of the chemiluminescence was found to be proportional to the hydroquinone concentration. We suggest that the rapid (measurement time, 60 s) and virtually solvent-free (solvent volume, <2 mL) chemiluminescent method described here for quantifying hydroquinone content may be an alternative to HPLC analysis.

The application of (-)-epigallocatechin gallate in preparation of an antioxidant dialysate.

Hemodialysis can remove uremic solutes but this treatment induces oxidative stress in uremic patients because of hemo-incompatibility. Therefore, we hypothesised that an antioxidant dialysate (a dialysate containing antioxidant(s)) would provide antioxidant defence in uremic patients during hemodialysis. Several herbal extracts were studied and measurements of antioxidant power and stability assays indicated that epigallocatechin gallate (EGCG) was the best of those tested for use as an antioxidant dialysate (EGCG dialysate). We observed that EGCG dialysate could provide the highest level of antioxidant defence at a dialysate flow rate of 500 ml/min and a blood flow rate of 200 ml/min. In addition, some important parameters for hemodialysis were calculated for supporting the protective role of EGCG dialysate. This is the first description of the preparation of an antioxidant dialysate. We suggest that EGCG dialysate will reduce the level of oxidative stress in hemodialysis patients, leading to a decrease of complications associated with oxidative damage.

Efficacy of epigallocatechin-3-gallate and Amla (Emblica officinalis) extract for the treatment of diabetic-uremic patients.

Uremic patients with diabetes suffer from high levels of oxidative stress due to regular hemodialysis therapy (neutrophil activation induced by hemo-incompatibility between the hemodialyser and blood) and complications associated with diabetes. Several plasma biomarkers were screened in 13 uremic diabetic patients after receiving the mixture of (-)-epigallocatechin gallate (EGCG), a major component of green tea extract, and Amla extract (AE), from Emblica officinalis, the Indian gooseberry, for 3 months. We found that oral administration of a 1:1 mixture of EGCG and AE for 3 months significantly improved antioxidant defense as well as diabetic and atherogenic indices in uremic patients with diabetes. Furthermore, no significant changes in hepatic function, renal function, or inflammatory responses were observed. These results suggest that a 1:1 combination of EGCG and AE is a safe and effective treatment for uremic patients with diabetes.

Low-density lipoprotein (LDL) apheresis reduces atherogenic and oxidative markers in uremic patients with hyperlipidemia.

Uremic patients with hyperlipidemia are classified at high atherogenic risk due to oxidative stress induced by regular hemodialysis process (hemoincompatibility) and a high level of oxidized low-density lipoprotein (ox-LDL). This study aimed to investigate whether LDL apheresis was capable of reducing oxidative and atherogenic markers in uremic patients with hyperlipidemia. We found that oxidative metabolites (methylquanidine, dityrosine, and ox-LDL) and atherogenic markers (lipoprotein (a), LDL, and LDL/HDL ratio) were significantly reduced (P < 0.05) after LDL apheresis. On the other hand, plasma total antioxidant status (TAS) was not influenced after LDL apheresis. Our results suggest that LDL apheresis reduces oxidative and atherogenic markers and do not influence plasma TAS in uremic patients with hyperlipidemia. This may lead to a decreased risk of atherosclerosis in these patients. However, supplementation of dietary proteins may be necessary because of the removal of some "useful" proteins (e.g., albumin and globulin) after LDL apheresis.

New analytical method for investigating the antioxidant power of food extracts on the basis of their electron-donating ability: comparison to the ferric reducing/antioxidant power (FRAP) assay.

Several analytical approaches are available for investigating the antioxidant power for antioxidants, and they are based on a variety of chemical principles, such as oxygen radical absorbance capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing/antioxidant power (FRAP). This paper reports a new rapid method for investigating antioxidant power on the basis of the electron-donating ability. This method is called chemiluminescence analysis of antioxidant power (CAAP). The electrons donated from antioxidants are capable of inducing chemiluminescence in the presence of lucigenin and a base. Thus, the intensity of chemiluminescence induced by antioxidants is proportional to their electron-donating ability (antioxidant power). It was found that the correlation between CAAP and FRAP was positive (r = 0.959) and statistically significant (p < 0.05). In addition to the FRAP assay, the rapid CAAP assay is convenient for investigating the antioxidant power of herbal extracts.

Supplementation of Emblica officinalis (Amla) extract reduces oxidative stress in uremic patients.

Emblica Officinalis (also known as Amla or Indian Gooseberry), a natural, traditional and functional food in Asia, has physiological benefits such as hepato-, cyto- and radio- protection, as well as hypolipidemic effects. In addition, Amla often functions as a potent antioxidant due to the high level of ascorbic acid (ranging from 1,100 to 1,700 mg/100 g of fruit) in its fruit. The aim of this study was to determine whether supplementation with Amla extract could reduce oxidative stress in patients with uremia. The findings show that supplementation with Amla extract for 4 months reduced the plasma oxidative marker, 8-iso-prostaglandin, (M0 vs. M4 = 1415 +/- 1234 pg/ml vs. 750 +/- 496 pg/ml, p < 0.05) and increased plasma total antioxidant status (TAS) (M0 vs. M4 = 2.32 +/- 0.14 mM vs. 2.55 +/- 0.24 mM, p < 0.05) in uremic patients. On the other hand, there were no significant differences observed in liver function (GOP and GPT), renal function (creatinine, blood urea nitrogen and uric acid), diabetic index (plasma glucose and adiponectin) and atherogenic index (LDL/HDL ratio, total cholesterol and homocysteine) in patients treated with Amla for 4 months. Our data suggest that Amla supplementation may increase plasma antioxidant power and decrease oxidative stress in uremic patients. However, Amla extract did not influence hepatic or renal function, or diabetic and atherogenic indices in uremic patients.

Antioxidant evaluation of three adaptogen extracts.

Adaptogens are harmless herbs which have pharmaceutical benefits due to their balancing, regulative and tonic functions. However, despite these medicinal effects, the antioxidant potential of adaptogens is rarely mentioned. This study investigated the antioxidant potential of 3 adaptogen extracts, Rhodiola rosea (golden root), Eleutherococcus senticosis (Siberian ginseng) and Emblica officinalis (Indian gooseberry, Amla). The results of this study showed that R. rosea had the highest potential for singlet oxygen scavenging, hydrogen peroxide scavenging, ferric reducing, ferrous chelating and protein thiol protection than either of the other 2 extracts. E. senticosis, on the other hand, showed the best potential for hypochlorite scavenging. In addition, the polyphenol content in the 3 adaptogen extracts followed the order: R. rosea, E. officinalis and E. senticosis. Our data suggest that the antioxidant potential of the 3 adaptogen extracts was proportional to their respective polyphenol content. The supplementation of adaptogen extracts containing high levels of polyphenols may not only have adaptogen properties, but may decrease the risk of complications induced by oxidative stress.