Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure.
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ABSTRACT:
SUBMITTER: Peng YH
PROVIDER: S-EPMC4639770 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Inflammation is in a wide spectrum of retinal diseases, causing irreversible blindness and visual impairment. We have previously demonstrated that Green Tea Extract (GTE) is a potent anti-inflammatory agent for anterior uveitis. Here we investigated the anti-inflammatory effect of GTE on lipopolysaccharides (LPS)-induced retinal inflammation in rats and explored the underlying mechanism. Adult rats were injected with LPS and GTE was administered intra-gastrically at 2, 8, 26 and 32?hours post-injection. Staining of whole-mount retina showed that the number of activated microglia cells was significantly increased at 48?hours post-injection, which was suppressed after GTE treatment in a dose-dependent manner. Activation of astrocytes and Müller glia in the retina was also suppressed after GTE treatment. Meanwhile, GTE reduced the expression of pro-inflammatory cytokines including IL-1?, TNF-? and IL-6 in retina and vitreous humor. These anti-inflammatory effects were associated with a reduced phosphorylation of STAT3 and NF-?B in the retina. Furthermore, the surface receptor of EGCG, 67LR, was localized on the neurons and glia in the retina. These findings demonstrate that GTE is an effective agent in suppressing LPS-induced retinal inflammation, probably through its potent anti-oxidative property and a receptor-mediated action on transcription factors that regulate production of pro-inflammatory cytokines.
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Project description:Green tea is made from unfermented dried leaves from Camellia sinensis and has been consumed by humans for thousands of years. For nearly as long, it has been used as a folk remedy for a wide array of diseases. More recently, a large number of in-vitro and in-vivo scientific studies have supported this ancient contention that the polyphenols from green tea can provide a number of health benefits. Since these compounds are clearly safe for human consumption and ubiquitous in the food supply, they are highly attractive as lead compounds for drug discovery programs. However, as drugs, they are far from optimum. They are relatively unstable, poorly absorbed, and readily undergo a number of metabolic transformations by intestinal microbiota and human enzymes. Further, since these compounds target a wide array of biological systems, in-vivo testing is rather difficult since effects on alternative pathways need to be carefully eliminated. The purpose of this review is to discuss some of the challenges and benefits of pursuing this family of compounds for drug discovery.
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Project description:AIM: Liguzinediol is a novel derivative of ligustrazine isolated from the traditional Chinese medicine Chuanxiong (Ligusticum wallichii Franch), and produces significant positive inotropic effect in isolated rat hearts. In this study we investigated the effects of liguzinediol on a rat model of heart failure. METHODS: To induce heart failure, male SD rats were injected with doxorubicin (DOX, 2 mg/kg, ip) once a week for 4 weeks. Then the rats were administered with liguzinediol (5, 10, 20 mg·kg(-1)·d(-1), po) for 2 weeks. Hemodynamic examination was conducted to evaluate heart function. Myocardial cell apoptosis was examined morphologically. The expression of related genes and proteins were analyzed using immunohistochemical staining and Western blot assays, respectively. RESULTS: Oral administration of liguzinediol dose-dependently improved the heart function in DOX-treated rats. Electron microscopy revealed that liguzinediol (10 mg·kg(-1)·d(-1)) markedly attenuated DOX-induced injury of cardiomyocytes, and decreased the number of apoptotic bodies in cardiomyocytes. Furthermore, liguzinediol significantly decreased Bax protein level, and increased Bcl-2 protein level in cardiomyocytes of DOX-treated rats, led to an increase in the ratio of Bcl-2/Bax. Moreover, liguzinediol significantly decreased the expression of both cleaved caspase-3 and NF-κB in cardiomyocytes of DOX-treated rats. Administration of digitalis (0.0225 mg·kg(-1)·d(-1)) also markedly improved the heart function and the morphology of cardiomyocytes in DOX-treated rats. CONCLUSION: Liguzinediol improves the heart function and inhibits myocardial cell apoptosis in the rat model of heart failure, which is associated with regulating Bcl-2, Bax, caspase-3 and NF-κB expression.
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Project description:BACKGROUND: Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. AIMS: To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. METHODS: Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)-galactosamine hydrochloride. The parameters assessed included; systemic, hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99mTc methylene diphosphonate and 99mTc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14C aminopyrine breath test). RESULTS: Progressive liver dysfunction was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 36, 42, and 48 hours after administration of D-galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function (r = 0.8, p < 0.0001). CONCLUSIONS: The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function.
| S-EPMC1727229 | biostudies-other
Project description:This study has investigated the metabolic effects of catechin-rich green tea (GT) and its formulation with ascorbic acid (AA) on the Zucker rat model of type 2 diabetes. AA is used to protect the GT catechins during digestion and increase bioavailability. Thirty two Zucker diabetic fatty (ZDF) rats were randomly divided into four groups (n=8 in each group) and treated with water, GT, AA and GT+AA respectively for five weeks. Urinary metabolic profiles were determined using 1H NMR spectroscopy. Fourteen metabolites were identified and their 24-hr excretions were quantified. Changes in the 14 metabolites demonstrated differential treatment effects on the metabolism of ZDF rats. GT and AA were found to be able to independently reduce urinary excretions of most metabolites that were over-excreted in the control diabetic rats, such as oxidative stress marker metabolites and TCA cycle metabolites. GT showed a great potential in controlling metabolic acidosis by suppressing the excretion of lactic acid and acetic acid from diabetic rats and GT+AA showed a remarkably stronger suppression than GT while AA was unable to suppress these two acids. Further investigation is needed to better understand the role of GT and/or formulated GT in altering the metabolic pathways in the diabetic animal model as well as in humans.
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Project description:Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n?=?12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1?, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1? and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats.
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Project description:Salusin-β is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin-β in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin-β on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin-β shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-β, leptin and visfatin levels and the salusin-β protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin-β gene knockdown. Salusin-β knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin-β knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin-β contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.
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Project description:The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional preformulation methods have been employed to improve the bioavailability of EGCg. However, these methods have limitations that hinder the development of EGCg as an effective therapeutic agent. In this study, we have utilized the basic concepts of crystal engineering and several crystallization techniques to screen for various solid crystalline forms of EGCg and evaluated the efficacy of crystal engineering for modulating the pharmacokinetics of EGCg. We synthesized and characterized seven previously undescribed crystal forms of EGCg including the pure crystal structure of EGCg. The aqueous solubility profiles of four new EGCg cocrystals were determined. These cocrystals were subsequently dosed at 100 mg EGCg per kg body weight in rats, and the plasma levels were monitored over the course of eight hours following the single oral dose. Two of the EGCg cocrystals were found to exhibit modest improvements in relative bioavailability. Further, cocrystallization resulted in marked effects on pharmacokinetic parameters including Cmax, Tmax, area under curve, relative bioavailability, and apparent terminal half-life. Our findings suggest that modulation of the pharmacokinetic profile of EGCg is possible using cocrystallization and that it offers certain opportunities that could be useful during its development as a therapeutic agent.
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Project description:IntroductionGreen tea extract has anti-inflammatory and antioxidant effects which improve dyslipidemia and decrease adipose tissue depots associated with hyperlipidic diet consumption.ObjectiveTo evaluate the effect of green tea extract consumption by rats during pregnancy and lactation on the metabolism of their offspring that received control or high-fat diet with water during 10 weeks after weaning.MethodsWistar rats received water (W) or green tea extract diluted in water (G) (400 mg/kg body weight/day), and control diet (10 animals in W and G groups) during pregnancy and lactation. After weaning, offspring received water and a control (CW) or a high-fat diet (HW), for 10 weeks. One week before the end of treatment, oral glucose tolerance test was performed. The animals were euthanized and the samples were collected for biochemical, hormonal and antioxidant enzymes activity analyses. In addition, IL-10, TNF-?, IL-6, and IL-1? were quantified by ELISA while p-NF-?Bp50 was analyzed by Western Blotting. Repeated Measures ANOVA, followed by Tukey's test were used to find differences between data (p < 0.05).ResultsThe consumption of high-fat diet by rats for 10 weeks after weaning promoted hyperglycemia and hyperinsulinemia, and increased fat depots. The ingestion of a high-fat diet by the offspring of mothers who consumed green tea extract during pregnancy and lactation decreased the inflammatory cytokines in adipose tissue, while the ingestion of a control diet increased the same cytokines.ConclusionOur results demonstrate that prenatal consumption of green tea associated with consumption of high-fat diet by offspring after weaning prevented inflammation. However, maternal consumption of the green tea extract induced a proinflammatory status in the adipose tissue of the adult offspring that received the control diet after weaning.
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Project description:Consumption of polyphenols and dietary fiber as part of a normal diet is beneficial to human health. In this study, we examined whether different amounts of dietary soluble fiber (pectin) affect the absorption and metabolism of polyphenols from blackcurrant and green tea in rats. After 28 days, the rats fed blackcurrant and green tea with pectin (4 or 8%) had significantly lower body weight gain and food intake compared to the rats fed a control diet. Rats fed a blackcurrant and green tea diet with 8% pectin had significantly higher fecal nitrogen output and lower protein digestibility. No polyphenols were observed in the urine, feces and plasma of rats fed the control diet. Parent catechins and flavonols were absent in urine obtained from all diet groups. Gallocatechin glucuronide was only observed in the plasma of rats fed the blackcurrant and green tea diet without pectin. Meanwhile, epicatechin and catechin gallate were present in the feces of rats fed a blackcurrant and green tea diet with and without 4% pectin. Pectin (4 or 8%) added to the blackcurrant and green tea diet increased the plasma antioxidant capacity in rats. Inclusion of pectin in the diet altered the host absorption and metabolism of polyphenols from blackcurrant and green tea.
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