Effects of Longevinex (modified resveratrol) on cardioprotection and its mechanisms of action

2010 ◽  
Vol 88 (11) ◽  
pp. 1017-1025 ◽  
Author(s):  
Subhendu Mukherjee ◽  
Diptarka Ray ◽  
Istvan Lekli ◽  
Istvan Bak ◽  
Arpad Tosaki ◽  
...  
Keyword(s):  
Rice Bran ◽  
Nuclear Translocation ◽  
Sprague Dawley ◽  
Akt Phosphorylation ◽  
Sprague Dawley Rats ◽  
Aging Properties ◽  
Considerable Debate ◽  
Enhanced Expression ◽  
Prolonged Feeding ◽  
Survival Signals

Although resveratrol has been proven to possess diverse health benefits, several recent reports have demonstrated conflicting results on some aspects of its effects, including its anti-aging properties. Considerable debate appears to exist on the dose and bioavailability of resveratrol, leading to the controversies on its effectiveness. To resolve the problem, we designed a study with a resveratrol formulation that contained resveratrol supplemented with 5% quercetin and 5% rice bran phytate (commercially known as Longevinex). These ingredients were micronized to increase the bioavailability. Sprague–Dawley rats were gavaged with either Longevinex or vehicle (5% quercetin plus 5% rice bran phytate), and rats were sacrificed after 1 or 3 months, when isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Longevinex-treated hearts, irrespective of the duration of treatments, revealed superior cardiac performance, reduced infarct size, and induction of survival signals as evidenced by increased Bcl2/Bax ratio and enhanced Akt phosphorylation. In contrast, LC3-II and Beclin were enhanced significantly after 3 months of Longevinex treatment, suggesting that autophagy occurred only after feeding Longevinex to rats for a prolonged period of time. Corroborating with the results of autophagy, Sirt1 and Sirt3 increased significantly only after 3 months of Longevinex treatment, suggesting that enhanced expression of Sirts correlated with induction of autophagy. In concert, Longevinex caused phosphorylation and nuclear translocation of FoxO1, FoxO3a, and FoxO4, indicating involvement of FoxOs with autophagy. Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.

Abstract 3880: GRK2 Inhibition Prevents Development Of Cardiac Insulin Resistance And Impaired Glucose Uptake In Post Ischemic Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michele Ciccarelli ◽  
Giuseppe Rengo ◽  
Kurt Chuprun ◽  
Gaetano Santulli ◽  
Bruno Trimarco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Uptake ◽  
Fluorescent Protein ◽  
Sprague Dawley ◽  
Myocardial Glucose Uptake ◽  
Akt Phosphorylation ◽  
Neonatal Cardiomyocytes ◽  
Sprague Dawley Rats ◽  
Green Fluorescent ◽  
And Function

The beta adrenergic receptor (βAR) kinase, GRK2, is upregulated and participates to the evolution of heart failure (HF) through downregulation and desensitization of βARs. Recent studies showed that this molecule affects insulin signaling and reduce glucose uptake in hepatocytes and adipocytes. We hypothesized that in HF, GRK2 reduces cardiac performance also through inhibition of cardiac glucose metabolism. In 12 week old Sprague/Dawley rats, we measured cardiac glucose uptake by PET 3 days, 3 and 6 weeks after myocardial infarction (MI). Function and cardiac dimensions were measured by echocardiography. We observed that glucose uptake was reduced in animal post-MI at 3 and 6 weeks respect to healthy animals (3 rd week: 1.3±0.22 vs 2.1±0.3; 6 th week: 1±0.1 vs 2.4±0.2, ml/min/g, p<0.05). No difference was observed in glucose uptake acutely after surgery. Echo showed cardiac dilation and reduced function at 6 weeks (LVD: 9.2± 0.3 vs 7.2± 0.4 mm; EF: 42%±1.1 vs 66%±2.2, p<0.05, Sham vs MI). To inhibit GRK2 in the heart during post-ischemic HF, we delivered the GRK2 inhibitor βARKct by adeno-associated type 6 virus (AAV6) to the left ventricle before induction of the MI. As a control we treated rats with AAV6 encoding for the green fluorescent protein (GFP). Cardiac dilation and function were preserved after 6 weeks post MI in AAV6 βARKct respect to AAV6GFP rats (LVD: 7.73 ±0.25 vs 9.9 ±0.8 mm; EF: 55%±2.25 vs 44%±2, p<0.05). Glucose uptake was better preserved in AAV6βARKct rats after 3 and 6 weeks post MI respect to AAV6GFP group (3rd week: 2.3±0.3 vs 1.2±0.2; 6th week: 1.8±0.2 vs 1.1±0.05, ml/min/g, p<0.05). Since Akt mediates most of the anabolic effects of insulin in cells, we evaluated the effects of GRK2 overexpression by adenovirus (ADGRK2) in neonatal cardiomyocytes (NRVMs) on Akt phosphorylation later on insulin stimulation (ins, 10 – 6 M). As control we induced overexpression of GFP by adenovirus (ADGFP). We observed reduced activation of Akt in presence of GRK2 overexpression as compared to the ADGFP treated cells (1.2±0.2- vs. 3.5±0.4- fold activation over basal, p<0.05). Our data show that post MI, impaired glucose extraction precedes development of HF, and that early GRK2 inhibition prevents impaired myocardial glucose uptake and HF development.

Repeated restraint stress upregulates rat sulfotransferase 1A1

2018 ◽  
Vol 30 (2) ◽  
pp. 265-273
Author(s):  
Rajiv Balyan ◽  
Ma Cai ◽  
Wenhong Zhao ◽  
Zhao Dai ◽  
Yujia Zhai ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Biological Activities ◽  
Male Rats ◽  
Transcriptional Level ◽  
Sprague Dawley ◽  
Metabolizing Enzymes ◽  
Sprague Dawley Rats ◽  
Repeated Restraint Stress ◽  
Enhanced Expression ◽  
Hormone Homeostasis

Abstract BackgroundSulfotransferases (SULTs) are phase II drug-metabolizing enzymes. SULTs also regulate the biological activities of biological signaling molecules, such as various hormones, bile acids, and monoamine neurotransmitters; therefore, they play critical roles in the endocrine and nervous systems. People are subject to various kinds of physical, chemical, toxicological, physiological, and psychological stresses at one time or another. The study of the effects produced by stress may lead to finding novel remedies for many disease conditions. The effect of repeated restraint stress on rat SULT expression has not been studied. MethodsThis study involves the effect of repeated restraint stress on SULT1A1 expressions. Male Sprague-Dawley rats (n=4) were subjected to repeated restraint stress 2 h/day for 7 days. Protein and RNA expression of SULT1A1 were analyzed by western blot and quantitative real time reverse transcription polymerase chain reaction, respectively, in important tissues. ResultsWe observed that repeated restraint stress increased the expression of SULT1A1 in the liver, adrenal glands, cerebellum, hypothalamus, and cerebral cortex in male rats. Patterns of enhanced expression were observed at both mRNA and protein level, indicating that repeated restraint stress stimulates enzyme expression at the transcriptional level. ConclusionsChanges of SULT1A1 expression in important tissues caused by repeated restraint stress will have a significant effect on drug metabolism and xenobiotics detoxification. The significant changes in endocrine glands and brain sections may also cause disturbances in hormone homeostasis, therefore leading to disease conditions. This report provides clues for the understanding of the effect of stresses on health.

scholarly journals Cardioprotective Effect of Danhong Injection against Myocardial Infarction in Rats Is Critically Contributed by MicroRNAs

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jingrui Chen ◽  
Jing wei ◽  
John Orgah ◽  
Yan Zhu ◽  
Jingyu Ni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Danhong Injection ◽  
Sprague Dawley Rats ◽  
Masson Staining

Background. Danhong injection (DHI) has been mainly used for the treatment of myocardial infarction, atherosclerosis, and coronary heart disease in clinical practice. Our previous studies have shown that DHI improves ventricular remodeling and preserves cardiac function in rats with myocardial infarction (MI). In this study, we focused on the potential mechanism of DHI in protecting cardiac function in MI rats. Methods. Sprague-Dawley rats were subjected to ligation of the left anterior descending coronary artery (LAD) to prepare a myocardial infarction (MI) model. After 14 day DHI intervention, cardiac function was measured by echocardiography and myocardial fibrosis was assessed by Masson staining. Differentiated miRNAs were screened using rat immunopathology miScript miRNA PCR arrays, and their results were verified by RT-PCR, immunofluorescence, and immunoblotting. Results. DHI treatment significantly reduced infarct size and improved cardiac function and hemodynamics in MI rats by echocardiography and morphology. miRNA PCR array results showed that DHI reversed 25 miRNAs known to be associated with inflammation and apoptosis. Moreover, the expression of inflammatory factors TNF-α, IL-1β, and IL-6 was significantly reduced in the treated DHI group. Mechanistically, DHI downregulated the inflammatory transcription factor NF-κB (as reflected by inhibition of NF-κB p65 nuclear translocation and phosphorylation of the IκBα). Conclusions. DHI is effective in mitigating inflammation associated with MI by preventing NF-κB nuclear translocation and regulating miRNAs, thereby improving cardiac function in myocardial infarction rats.

Dermal toxicity study of rice bran supercritical CO2 extract in Sprague-Dawley rats

2015 ◽  
Vol 24 (3) ◽  
pp. 1167-1176
Author(s):  
Jae-Suk Choi ◽  
Eun Jin Cheon ◽  
Tae-Uk Kim ◽  
Woi-Sook Moon ◽  
Joo-Wan Kim ◽  
...  
Keyword(s):  
Rice Bran ◽  
Supercritical Co2 ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Dermal Toxicity ◽  
Sprague Dawley Rats ◽  
Supercritical Co2 Extract

Heat shock treatment suppresses angiotensin II-induced activation of NF-κB pathway and heart inflammation: a role for IKK depletion by heat shock?

2004 ◽  
Vol 287 (3) ◽  
pp. H1104-H1114 ◽  
Author(s):  
Yu Chen ◽  
André-Patrick Arrigo ◽  
R. William Currie
Keyword(s):  
Angiotensin Ii ◽  
Heat Shock ◽  
Nuclear Translocation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Mobility Shift ◽  
Iκb Kinase ◽  
Sprague Dawley Rats ◽  
Mobility Shift Assay ◽  
High Level

Heat shock (HS) proteins (Hsps) function in tissue protection through their chaperone activity and by interacting with cell signaling pathways to suppress apoptosis. Here, we investigated the effect of HS treatment on the nuclear factor (NF)-κB signaling pathway in the angiotensin II (ANG II) model of inflammation. Male Sprague-Dawley rats were divided into sham and HS-, ANG II-, and HS + ANG II-treated groups. HS treatment was administered 24 h before the initiation of ANG II infusion. HS treatment (42°C for 15 min) decreased 7-day ANG II-induced hypertension from 191 ± 4 to 147 ± 3 mmHg ( P < 0.01). Histological staining of hearts showed that HS treatment reduced ANG II-induced leukocyte infiltration, perivascular and interstitial inflammation, and fibrosis. Heart NF-κB nuclear translocation and activity, examined by Western blot analysis and electrophoretic mobility shift assay, was suppressed by HS treatment. HS treatment depleted IκB kinase-α (IKK-α) and phosphorylated IKK-α and suppressed the depletion of IκB-α and the accumulation of phosphorylated IκB-α. HS treatment blocked ANG II induced expression of IL-6 and ICAM-1 in the heart. ANG II and HS treatment induced high-level expression of Hsp27 and Hsp70 and their phosphorylation. Phosphorylated isoforms of Hsp27 and Hsp70 may play an important role in protecting the heart against ANG II-induced inflammation.

scholarly journals Supplementation with Fermented Rice Bran Attenuates Muscle Atrophy in a Diabetic Rat Model

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2409 ◽  
Author(s):  
Tubagus Bahtiar Rusbana ◽  
Afifah Zahra Agista ◽  
Wahyu Dwi Saputra ◽  
Yusuke Ohsaki ◽  
Kouichi Watanabe ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Rice Bran ◽  
Rat Model ◽  
Muscle Size ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Diabetic Rat Model

Fermented rice bran (FRB), a prospective supplement, has been proven to ameliorate certain medical conditions. However, its nutraceutical effect on muscle atrophy has never been investigated. The present study aimed to evaluate the effect of FRB on muscle atrophy in a streptozotocin (STZ)-induced diabetic rat model. Three groups of Sprague-Dawley rats, namely the control, STZ, and FRB groups, were treated as follows. The diabetic groups (STZ and FRB) were injected intraperitoneally with STZ (40 mg/kg BW), whereas the control group was injected with the vehicle. The STZ and control groups were fed the AIN93M diet, and the FRB group was fed 10% of FRB based on the AIN93M diet. The diabetic groups had reduced muscle size compared to the control group; however, these changes were alleviated in the FRB group. Moreover, the FRB group had a significantly lower expression of FBXO32/Atrogin-1 and TRIM63/MuRF1 (p < 0.05) due to blocked NF-κB activation. In conclusion, the anti-inflammatory effect of FRB may be beneficial for ameliorating muscle atrophy in diabetic conditions.

scholarly journals Preventive Inositol Hexaphosphate Extracted from Rice Bran Inhibits Colorectal Cancer through Involvement of Wnt/β-Catenin and COX-2 Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nurul Husna Shafie ◽  
Norhaizan Mohd Esa ◽  
Hairuszah Ithnin ◽  
Abdah Md Akim ◽  
Norazalina Saad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rice Bran ◽  
Anticancer Agent ◽  
Dietary Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Colorectal Tumorigenesis ◽  
Chemopreventive Agent ◽  
Sprague Dawley Rats ◽  
Cox 2

Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP6extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP6was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis.β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP6markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP6had also markedly decreasedβ-catenin and COX-2 in colon tumors. Thus, the downregulation ofβ-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP6and thereby act as a potent anticancer agent.

Abstract 046: High Fructose Intake Increases Phosphorylation and Trafficking of the Na/K/2Cl Cotransporter (NKCC22) In Rat Thick Ascending Limbs

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Gustavo R Ares ◽  
Mohammed Z Haque ◽  
Pablo A Ortiz
Keyword(s):  
Drinking Water ◽  
Apical Membrane ◽  
Control Diet ◽  
Caloric Intake ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Added Sugars ◽  
Sprague Dawley Rats ◽  
Enhanced Expression ◽  
Salt Sensitive Hypertension

A third of the US population consumes 20-40% of their caloric intake from added sugars with half of those calories from fructose. Fructose consumption is linked to salt-sensitive hypertension in humans and rodents. We found that feeding Sprague-Dawley rats 20% fructose in their drinking water did not increase blood pressure unless a high salt diet was added. The thick ascending limb (TAL) reabsorbs 25% of filtered NaCl, primarily via NKCC2. NKCC2 activity is increased by enhanced expression at the apical membrane and phosphorylation at Thr 96/101 . We found enhanced NKCC2 activity and trafficking in genetic models of salt-sensitive hypertension. However, the effect of fructose on NKCC2 regulation is unknown. Thus, we hypothesized that a fructose enriched diet stimulates NKCC2 activity. Sprague-Dawley rats were fed control diet or 20% fructose in drinking water for 1 week. TALs were isolated and phosphorylated and total NKCC2 was measured by surface biotinylation followed by western blot. A fructose-enriched diet increased surface-to-intracellular NKCC2 ratio by 60 ± 23% ( p< 0.05) and increased NKCC2 phosphorylation at Thr 96/101 by 8.02 ± 2.67 fold ( p <0.05). NKCC2 phosphorylation at the plasma membrane was also increased by 4.5 fold ( p <0.05). Total NKCC2 expression was reduced by 40.1 ± 8.9% ( p< 0.05). Since phosphorylation of NKCC2 at Thr 96/101 is mediated by STE20- and SPS1-related proline and alanine-rich kinases (SPAK) and oxidative stress-responsive kinase 1 (OSR1), we studied whether fructose stimulates expression and/or activity of SPAK/OSR1. Total SPAK/OSR1 expression was not enhanced by one week of a fructose diet. However, phosphorylation at Ser373 was enhanced by 2.8 ± 0.3 fold ( p< 0.05). We concluded that a fructose enriched diet increases phosphorylation and trafficking of NKCC2, enhancing its accumulation at the apical membrane. Moreover, a fructose diet increased SPAK/OSR1 kinases phosphorylation, suggesting they may be responsible for the enhanced NKCC2 phosphorylation. Our data suggest that a fructose-enriched diet promotes salt-sensitive hypertension in part by stimulating NKCC2 and TAL-dependent NaCl reabsorption.

scholarly journals Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation

2020 ◽  
Vol 21 (22) ◽  
pp. 8827
Author(s):  
Maria José Rodríguez ◽  
Francisca Herrera ◽  
Wendy Donoso ◽  
Iván Castillo ◽  
Roxana Orrego ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Fibrosis ◽  
Nuclear Translocation ◽  
D1 Protein ◽  
Hepatic Tissue ◽  
Lipid Mediator ◽  
Related Factor ◽  
Nuclear Factor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2–related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.

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