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ABSTRACT: Ginsenosides are the main active components of Panax ginseng. Structural changes in diol type ginsenosides along with generation of Maillard reaction products (MRPs) are strongly associated with increased free radical-scavenging activities. Ginsenoside Re, one of the major triol type ginsenosides of P. ginseng, possesses a hydrophobic four-ring steroid-like structure with hydrophilic sugar moieties at carbons-3 and -20. The aim of the present study was to identify changes in the structure, antioxidant and anticancer effects of ginsenoside Re upon Maillard reaction. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg(2), Rg(6) and F(4) by heat-processing. Free radical-scavenging activity of the ginsenoside Re-lysine mixture increased upon heat processing. This improved free radical-scavenging activity mediated by antioxidant MRPs, which were generated through Maillard reaction of a glucosyl moiety separated from carbon-20 of ginsenoside Re and lysine. The increased anticancer effect of ginsenoside Re-lysine mixture upon heat processing was mainly derived from the generation of less-polar ginsenosides through the regulation of Bcl-2 and Bax, as well as caspase-dependent apoptotic pathway. These results reported here have shed significant new lights on the mechanism of increased antioxidant and anticancer effects of P. ginseng upon heat processing.
Food Chemistry 06/2013; 138(2-3):876-83. · 3.65 Impact Factor
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ABSTRACT: Levodopa (L-DOPA) is widely used for symptomatic management in Parkinson's disease. We recently showed that (-)-epigallocatechin-3-gallate, a tea polyphenol, not only inhibits L-DOPA methylation, but also protects against oxidative hippocampal neurodegeneration (PLoS ONE, 5: e11951, 2010). In the present study, we sought to determine several other common dietary phenolics, namely, tea catechins [(+)-catechin and (-)-epicatechin] and a representative flavonoid (quercetin), for their ability to modulate L-DOPA methylation and to protect against oxidative hippocampal injury. A combination of in vitro biochemical assays, cell culture-based mechanistic analyses, and in vivo animal models was used. While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo. In addition, (+)-catechin strongly reduces glutamate-induced oxidative cytotoxicity in HT22 mouse hippocampal neurons in vitro through inactivation of the nuclear factor-κB signaling pathway. Administration of (+)-catechin also exerts a strong neuroprotective effect in the kainic acid-induced oxidative hippocampal neurodegeneration model in rats. In conclusion, (+)-catechin is a dietary polyphenolic that may have beneficial effects in L-DOPA-based treatment of Parkinson patients by inhibiting L-DOPA methylation plus reducing oxidative hippocampal neurodegeneration.
Brain research 11/2012; · 2.46 Impact Factor
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ABSTRACT: We have investigated the effects of Kangen-karyu, a Chinese prescription, on the lipid metabolism and oxidative stress in a type 2 diabetes model.
Male db/db mice were divided into three groups: control (vehicle), Kangen-karyu 100 or 200 mg/kg body weight/day orally administered mice. Age-matched non-diabetic m/m mice were used as a normal group.
The administration of Kangen-karyu reduced hyperglycaemia and hyperlipidaemia in db/db type 2 diabetic mice through a decline in the serum levels of glucose and lipids, and an improvement of lipoprotein profiles. The increased oxidative stress in db/db mice was attenuated by the administration of Kangen-karyu through inhibiting the generation of reactive oxygen species and lipid peroxidation. The enhanced hepatic triglyceride and total cholesterol levels of the db/db mice were significantly reduced by Kangen-karyu administration through down-regulation of sterol regulatory element-binding protein-1 and lipogenic enzymes in liver. Furthermore, the expressions of hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 and inducible nitric oxide synthase protein levels were also augmented in db/db mice. However, Kangen-karyu reduced the expressions of these inflammatory proteins by inhibiting NF-κB activation in db/db type 2 diabetes.
This study suggests that Kangen-karyu may improve oxidative stress via the regulation of dyslipidaemia in type 2 diabetes.
The Journal of pharmacy and pharmacology. 01/2011; 63(1):111-9.
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ABSTRACT: The prevention and treatment of diabetic complications are considered to be the most important for the general care of diabetic patients. We have been conducting pre-clinical animal experiments related to diabetes using kangen-karyu, a Chinese prescription, to examine its therapeutic potential. In the present study, we further studied the anti-diabetic mechanism of kangen-karyu, especially on the regulation of hyperglycemia-induced hepatic oxidative stress and inflammation in db/db mice. Kangen-karyu (100 or 200 mg/kg body weight/day, per os (p.o.) was administered every day for 18 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. The administration of kangen-karyu decreased the elevated serum and hepatic glucose concentration in db/db mice. The elevated expressions of p22(phox) and Nox-4 proteins (reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits) were significantly decreased after kangen-karyu treatments. The oxidative stress-related markers in hepatic tissue (reactive oxygen species, reduced glutathione/oxidized glutathione ratio, and thiobarbituric acid-reactive substance) were also significantly ameliorated by the kangen-karyu treatments. The db/db mice exhibited the up-regulation of nuclear factor-κBp65, cyclooxygenase-2, and inducible nitric oxide synthase levels in the liver; however, kangen-karyu treatment significantly reduced those expressions. Taking these into consideration, our findings support the therapeutic evidence for kangen-karyu ameliorating the development of diabetic hepatic damages via regulating oxidative stress and inflammation.
Biological & Pharmaceutical Bulletin 01/2011; 34(3):383-8. · 1.66 Impact Factor
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ABSTRACT: Previously, we have reported that Corni Fructus possessed hypoglycemic and hypocholesterolemic effects in streptozotocin-induced type 1 diabetic rats and diet-induced hypercholesterolemic rats. Herein, we have focused on the effect and mechanism of loganin, a major iridoid glycoside of Corni Fructus, on the type 2 diabetic db/db mice. Loganin was orally administered to db/db mice at a dose of 20 or 100 mg/kg body weight daily for 8 weeks. The biochemical factors and expressions of protein and mRNA related to lipid metabolism, inflammation, advanced glycation endproducts, and its receptor were measured. In loganin-treated db/db mice, hyperglycemia and dyslipidemia were ameliorated in both the serum and hepatic tissue; however, in the kidney, only triglyceride was reduced. The enhanced oxidative stress was alleviated by loganin through a decrease in thiobarbituric acid-reactive substances (liver and kidney) and reactive oxygen species (serum, liver, and kidney), as well as augmentation of the oxidized to reduced glutathione ratio (liver and kidney). The marked lipid-regulatory effect of loganin was exerted in the liver of type 2 diabetic mice via suppressing mRNA expressions related to lipid synthesis and adjusting the abnormal expression of peroxisome proliferator-activated receptor α and sterol regulatory-element binding protein in the nucleus. Furthermore, loganin inhibited advanced glycation endproduct formation and the expression of its receptor, and nuclear factor-kappa B-induced inflammation in the hepatic tissue of db/db mice. Loganin exhibits protective effects against hepatic injury and other diabetic complications associated with abnormal metabolic states and inflammation caused by oxidative stress and advanced glycation endproduct formation.
European journal of pharmacology 12/2010; 648(1-3):179-87. · 2.59 Impact Factor
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ABSTRACT: The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17β-estradiol (E₂) on hyperglycemia and islet β-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E₂ orally at 500 μg/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet β-cell proliferation. E₂ administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E₂ were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E₂ on islet cells was linked to the functions of the estrogen receptor α. Notably, these protective effects of E₂ on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E₂ can promote the regeneration of damaged pancreatic islets by stimulating β-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E₂ may be beneficial in diabetic patients with an accelerated loss of islet β-cells.
Toxicology and Applied Pharmacology 11/2010; 249(1):76-85. · 4.45 Impact Factor
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ABSTRACT: Kangen-karyu (KK) is a traditional Chinese prescription consisting of six different herbs. This study was conducted to investigate the anti-dementia effect of KK on aging-induced cognitive deficits and the underlying mechanism using senescence-accelerated mice prone (SAMP8).
Twenty-week old SAMP8 (older SAMP8) were used as an animal model of aging and age-matched senescence-resistant inbred strain (SAMR1) and 8-week-old SAMP8 (young SAMP8) were as controls. Older SAMP8 received daily administration of KK (100 mg/kg, p.o.) or water vehicle for 22 days.
Compared to the controls, older SAMP8 exhibited cognitive deficits in the object recognition and object location tests; however, KK improved the deficits caused by aging. Moreover, the older SAMP8 treated with vehicle exhibited reduced anxiety-like behavior in the elevated plus-maze test compared to SAMR1, but KK had no effect on emotional disorder of older SAMP8. The levels of biochemical factors related to neuro-plasticity and learning and memory; i.e., phosphorylated forms of N-methyl-D-aspartate receptor 1, Ca(2+)/calmodulin-dependent protein kinase II, and cyclic AMP-responsive element-binding protein, and brain-derived neurotrophic factor, were significantly decreased in older SAMP8 compared to those in the control animals. KK normalized the levels of these factors. Moreover, the mRNA and protein levels of vascular endothelial growth factor (VEGF) and its receptor type 2 in the cerebral cortices of older SAMP8 were down-regulated by aging, but these levels were reversed by KK.
These findings suggest that normalization of neuro-plasticity-related neuronal signaling and VEGF systems in the brain may be of the mechanisms underlying the ameliorative effects of KK on the cognitive deficits in older SAMP8.
Journal of ethnopharmacology 09/2010; 131(2):377-85. · 2.32 Impact Factor
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ABSTRACT: Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (</=5 microM), resveratrol exerted a significant growth-stimulatory effect in the MDA-MB-435s human cancer cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.
Molecular Carcinogenesis 08/2010; 49(8):750-9. · 3.16 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the beneficial effects of 7-O-galloyl-D-sedoheptulose (GS), isolated from Corni Fructus, on hepatic and renal lipid metabolisms and advanced glycation endproduct formation followed by oxidative stress and inflammation using type 2 diabetic mice. GS was orally administered to db/db mice at doses of 20 and 100 mg/kg body weight per day for 8 weeks, and its effects were compared with those of the vehicle in db/db and m/m mice. The serum, hepatic, and renal biochemical factors, and protein expressions related to lipid metabolism, inflammation, advanced glycation endproducts, and their receptors, were measured. After 8 weeks of GS treatment, elevation of serum adiponectin as well as an improvement of hepatic and renal functional parameters was shown in db/db mice, and significant reductions of lipids in serum, liver, and kidney were observed according to the down-regulation of sterol regulatory element-binding protein-1. Moreover, GS inhibited oxidative stress and advanced glycation endproduct formation and their receptor expressions in the liver and kidney of db/db mice. These results suggest that GS could effectively inhibit advanced glycation endproduct formation caused by oxidative stress and/or dyslipidemia in the liver and kidney of db/db mice. Furthermore, the augmented expression of nuclear factor-kappa B p65 and its related inflammatory protein expressions were down-regulated in GS-treated groups. In conclusion, GS could have hepato- and reno-protective effects against abnormal lipid metabolism and the reactive oxygen species-related formation of advanced glycation endproducts with inflammation in type 2 diabetes.
European journal of pharmacology 05/2010; 640(1-3):233-42. · 2.59 Impact Factor
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ABSTRACT: Chinese prescription Kangen-karyu is clinically used as a treatment for cardiovascular diseases, and we have reported the beneficial effects on chemically induced hyperlipidemic animal models. The present study was investigated to evaluate the hypolipidemic effect of Kangen-karyu in type 2 diabetic db/db mice which has not been explored yet.
Male db/db mice were divided into three groups, vehicle (control), Kangen-karyu 100, or 200 mg/kg body weight/day, and orally administered for 5 weeks every day. Age-matched non-diabetic m/m mice were used as a normal group.
Serum triglyceride (TG) and total cholesterol levels in db/db mice were increased compared with those of m/m mice. However, the administration of Kangen-karyu reduced hyperlipidemia in db/db mice through a decline in the serum levels of TG and total cholesterol. The hepatic TG and total cholesterol levels of db/db mice were markedly higher than those of m/m mice, but these elevated lipid levels were significantly reduced by 200 mg/kg Kangen-karyu administration. Also, oil red O staining showed that the increased lipid deposition level in the liver of db/db control mice was improved by Kangen-karyu administration. The expression of sterol regulatory element-binding protein-1 in the liver of db/db mice was significantly down-regulated by the administration of Kangen-karyu at a dose of 200 mg/kg body weight. Kangen-karyu caused a slight elevation in the expression of peroxisome proliferator-activated receptor alpha in the liver of db/db mice.
This study provides scientific evidence that Kangen-karyu improves hyperlipidemia and lipid deposition via the regulation of hepatic SREBP-1 expression in type 2 diabetic db/db mice.
Journal of ethnopharmacology 04/2010; 129(3):299-305. · 2.32 Impact Factor
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ABSTRACT: It was reported recently that resveratrol could sensitise a number of cancer cell lines to the anticancer actions of several other cancer drugs, including paclitaxel. In the present study, we further investigated whether resveratrol could sensitise human breast cancer cells to paclitaxel-induced cell death. Unexpectedly, we found that resveratrol strongly diminished the susceptibility of MDA-MB-435s, MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death in culture, although this effect was not observed in MCF-7 cells. Using MDA-MB-435s cells as a representative model, a similar observation was made in athymic nude mice. Mechanistically, the modulating effect of resveratrol was partially attributable to its inhibition of paclitaxel-induced G(2)/M cell cycle arrest, together with an accumulation of cells in the S-phase. In addition, resveratrol could suppress paclitaxel-induced accumulation of reactive oxygen species (ROS) and subsequently the inactivation of anti-apoptotic Bcl-2 family proteins. These observations suggest that the strategy of concomitant use of resveratrol with paclitaxel is detrimental in certain types of human cancers. Given the widespread use of resveratrol among cancer patients, this study calls for more preclinical and clinical testing of the potential benefits and harms of using resveratrol as a dietary adjuvant in cancer patients.
European journal of cancer (Oxford, England: 1990) 03/2010; 46(10):1882-91. · 4.12 Impact Factor
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ABSTRACT: A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.
Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.
These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration.
PLoS ONE 01/2010; 5(8):e11951. · 4.09 Impact Factor
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ABSTRACT: The present study sought to further investigate the in vitro and in vivo anticancer effects of a representative omega-3 fatty acid, docosahexaenoic acid (DHA), with a focus on assessing the induction of oxidative stress and apoptosis as an important mechanism for its anticancer actions.
In vitro studies showed that DHA strongly reduces the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and also promotes cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contribute critically to the induction of apoptotic cell death. Co-presence of antioxidants or selective inhibition or knockdown of caspase 8 each effectively abrogates the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals the 5% fish oil-supplemented diet for 6 weeks significantly reduces the growth of MCF-7 human breast cancer cells in vivo through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that the fish oil-supplemented diet significantly increases oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet increases the levels of DHA and eicosapentaenoic acid in both normal and tumorous mammary tissues by 329% and 300%, respectively.
DHA can strongly induce apoptosis in human MCF-7 breast cancer cells both in vitro and in vivo. The induction of apoptosis in these cells is selectively mediated via caspase 8 activation. These observations call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of human breast cancer.
PLoS ONE 01/2010; 5(4):e10296. · 4.09 Impact Factor
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ABSTRACT: The effects of heat-processed ginseng (HPG) and ginsenoside 20(S)-Rg(3) on the progression of renal damage in type 2 diabetic rats were investigated. Twenty-two-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into 4 orally administered groups: vehicle (diabetic control), HPG water extract (100 mg/kg) and 20(S)-Rg(3) (5, 10 mg/kg). Non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used as a normal group. OLETF rats showed markedly higher blood glucose, triglyceride, and total cholesterol levels than those of LETO rats. The elevated blood glucose level of OLETF rats was significantly lowered by 20(S)-Rg(3) administration. The elevated serum triglyceride and total cholesterol levels were significantly reduced by the administrations of HPG and 20(S)-Rg(3). The serum levels of thiobarbituric acid-reactive substance, an index of lipid peroxidation, were markedly increased in OLETF compared to LETO rats, but it was significantly reduced by HPG and 20(S)-Rg(3) administrations. The urinary protein level, an indicator of advanced diabetic nephropathy, of OLETF rats was 4.4 times higher than in LETO rats, but it was reduced significantly by the administrations of HPG and 20(S)-Rg(3). Creatinine clearance of OLETF rats was significantly increased after HPG and 20(S)-Rg(3) administrations. The elevation of inducible nitric oxide synthase and N(epsilon)-(carboxymethyl)lysine protein expressions in renal tissues of OLETF rats was prevented by 20(S)-Rg(3) administration. This study provides scientific evidence that 20(S)-Rg(3) prevents the progression of renal damage and dysfunction in type 2 diabetic rats via inhibiting oxidative stress and advanced glycation endproduct formation.
Biological & Pharmaceutical Bulletin 01/2010; 33(6):1077-81. · 1.66 Impact Factor
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ABSTRACT: The effect of morroniside on lipid metabolism and the inflammatory response in the liver of type 2 diabetes model mice was investigated in this study. Male C57BLKS/J db/db mice were divided into the three groups: control (vehicle), morroniside 20, or 100 mg/kg body weight-treated mice. The elevated serum triglyceride and alanine aminotransferase levels as well as hepatic glucose and lipids contents in db/db mice were significantly decreased by the 8-week oral administration of morroniside in a dose-dependent manner. The generations of hepatic thiobarbituric acid-reactive substances and reactive oxygen species induced by hyperglycemia and dyslipidemia were also significantly decreased by the administration of morroniside. In addition, the barometer of an antioxidative state, the oxidized to reduced glutathione ratio, in the liver of db/db mice was markedly increased by morroniside treatment. From protein analysis, the elevated expressions of nuclear factor-kappaBp65, cyclooxygenase-2, inducible nitric oxide synthase, and sterol regulatory element binding proteins (SREBP-1 and SREBP-2) were down-regulated in the liver of db/db mice. On the other hand, the administration of morroniside significantly increased hepatic peroxisome proliferator activated receptor alpha expression. These results suggest that morroniside would act as a regulator of hepatic inflammatory reactions and lipid metabolism in db/db mice.
Biological & Pharmaceutical Bulletin 10/2009; 32(10):1734-40. · 1.66 Impact Factor
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ABSTRACT: Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities.
Journal of medicinal food 09/2009; 12(4):714-21. · 1.39 Impact Factor
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ABSTRACT: Diabetes is the leading cause of end-stage renal failure, since glucose-dependent metabolic factors are synergistically activated within the diabetic kidney. Accordingly, in Japan, there is much debate over the health benefits of natural therapies to reduce these risk factors. In our previous study, we reported that Cornus officinalis SIEB. et ZUCC. possessed an antidiabetic effect via ameliorating glucose-mediated metabolic disorders as well as aminoguanidine, an inhibitor of advanced glycation endproduct (AGE) formation, with a renoprotective effect. The aim of the present study was to investigate the effect of 7-O-galloyl-D-sedoheptulose (GS) against diabetic oxidative stress and AGE formation. Streptozotocin-induced diabetic rats were orally administered GS for 20 d, and the changes in serum glucose levels, as well as those of body weight every 10 d were evaluated. In addition, glucose, fluorescent AGE, methylglyoxal, glycolaldehyde (GA), and immunoblotting analyses for heme oxygenase-1, receptor for AGE, N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, and GA-pyridine were performed in the kidney at the end of the experiment. The results obtained in this study demonstrated that 20 d of treatment with GS had beneficial effects on hypoglycemic and renal metabolic abnormalities, including renal glucose, oxidative stress, and AGE formation. Together, our data help to elucidate its potential therapeutic value against diabetic kidney disease.
Biological & Pharmaceutical Bulletin 05/2009; 32(4):657-64. · 1.66 Impact Factor
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ABSTRACT: In our previous study, we reported the renoprotective effect of Hachimi-jio-gan, a Chinese traditional prescription consisting of eight medicinal plants, and also reported the effect of Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a component of Hachimi-jio-gan, on diabetic nephropathy using diabetic rats. In this study, we investigated the effects of morroniside isolated from Corni Fructus on renal damage in streptozotocin-treated diabetic rats. Oral administration of morroniside at a dose of 20 or 100 mg/kg body weight/d for 20 d to diabetic rats resulted in significant decreases in increasing serum glucose and urinary protein levels. Moreover, the decreased levels of serum albumin and total protein in diabetic rats were significantly increased by morroniside administration at a dose of 100 mg/kg body weight/d. In addition, morroniside significantly reduced the elevated serum urea nitrogen level and showed a tendency to reduce creatinine clearance. Morroniside also significantly reduced the enhanced levels of serum glycosylated protein, and serum and renal thiobarbituric acid-reactive substances. Protein expressions related to the advanced glycation endproduct (AGE) level and actions, oxidative stress such as N(epsilon)-(carboxyethyl)lysine, as well as receptors for AGE and heme oxygenase-1 were increased in diabetic rats, but the levels were also significantly decreased by the administration of morroniside. This suggests that morroniside exhibits protective effects against diabetic renal damage by inhibiting hyperglycemia and oxidative stress. These results indicate that morroniside is one component partly responsible for the protective effects of Corni Fructus and Hachimi-jio-gan against diabetic renal damage.
Biological & Pharmaceutical Bulletin 08/2008; 31(7):1422-8. · 1.66 Impact Factor
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ABSTRACT: The inhibitors of advanced glycation endproduct and oxidative stress, as well as N-methyl-d-aspartate (NMDA) receptor antagonists have received considerable interest because of their close association with renoprotective effects. The therapeutic potential of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)), isolated from Panax ginseng, against streptozotocin-induced diabetic renal damage, was investigated in this study. The diabetic rats received 5, 10, and 20 mg/kg body weight/day of 20(S)-Rg(3) orally via gavage for fifteen consecutive days. The physiological abnormalities such as increases in water intake and urine volume of diabetic rats were significantly decreased by the 20 mg/kg body weight of 20(S)-Rg(3) administration. The elevated serum glucose, glycosylated protein, and thiobarbituric acid-reactive substance levels in diabetic rats were also significantly reduced by the 20(S)-Rg(3) administrations. Moreover, the renal dysfunction of diabetic rats was significantly ameliorated by the 20(S)-Rg(3) administrations in a dose-dependent manner. These beneficial effects on diabetic renal damage were related to the inhibitory effect of 20(S)-Rg(3) against NMDA receptor-mediated nitrosative stress.
European Journal of Pharmacology 07/2008; 591(1-3):266-72. · 2.52 Impact Factor
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ABSTRACT: Inhibitors of advanced glycation end products (AGEs) have potential as preventive agents against diabetic complications. In-vitro AGE inhibitory activity, transition metal chelating, and free radical scavenging activity tests have been used to screen for and identify effective AGE inhibitors. In an ongoing project to elucidate AGE inhibiting active components of heat-processed ginseng, maltol was selected for more detailed investigation. Although there are several lines of evidence concerning the antioxidant activity of maltol, the in-vitro and in-vivo inhibitory effects of maltol on AGE generation have not been evaluated. In the present study, the in-vitro AGE inhibitory effects and free radical scavenging activity of maltol were investigated. In addition, the in-vivo therapeutic potential of maltol against diabetic renal damage was tested using streptozotocin (STZ)-diabetic rats. Maltol showed a stronger AGE inhibitory effect than aminoguanidine, a well known AGE inhibitor. In addition, the hydroxyl radical scavenging activity of maltol on electron spin resonance (ESR) spectrometry was slightly stronger than that of aminoguanidine. Therefore, maltol was found to have stronger in-vitro AGE inhibiting activity compared with aminoguanidine. The administration of 50 mgkg(-1) per day of maltol suppressed the elevated serum levels of glycosylated protein, renal fluorescent AGEs, carboxymethyllysine, receptors for AGEs, and nuclear factor-kappaB p65 in diabetic control rats. These beneficial effects of maltol against STZ-diabetic renal damage were thought to result from its free radical scavenging and AGE inhibitory effects.
Journal of Pharmacy and Pharmacology 05/2008; 60(4):445-52. · 2.17 Impact Factor
