Gs-Rb1 Group Research Articles

Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway.

To investigate whether ginsenoside-Rb1 (Gs-Rb1) improves the CoCl-induced autophagy of cardiomyocytes via upregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. Ventricles from 1- to 3-day-old Wistar rats were sequentially digested, separated and incubated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 3 days followed by synchronization. Neonatal rat cardiomyocytes were randomly divided into 7 groups: control group (normal level oxygen), hypoxia group (500 μmol/L CoCl2), Gs-Rb1 group (200 μmol/L Gs-Rb1 + 500 μmol/L CoCl2), Ara A group (500 μmol/L Ara A + 500 μmol/L CoCl2), Ara A+ Gs-Rb1 group (500 μmol/L Ara A + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl2), AICAR group [1 mmol/L 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) + 500 μmol/L CoCl2], and AICAR+Gs-Rb1 group (1 mmol/L AICAR + 200 μmol/L Gs-Rb1 + 500 μmol/L CoCl2). Cells were treated for 12 h and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cardiac troponin I (cTnI) levels were detected by enzyme-linked immunosorbent assay (ELISA). AMPK activity was assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) ELISA assay. The protein expressions of Atg4B, Atg5, Atg6, Atg7, microtubule-associated protein 1A/1B-light chain 3 (LC3), P62, and active-cathepsin B were measured by Western blot. Gs-Rb1 significantly improved the cell viability of hypoxia cardiomyocytes (P<0.01). However, the viability of hypoxia-treated cardiomyocytes was significantly inhibited by Ara A (P<0.01). Gs-Rb1 increased the AMPK activity of hypoxia-treated cardiomyocytes. The AMPK activity of hypoxia-treated cadiomyocytes was inhibited by Ara A (P<0.01) and was not affected by AICAR =0.983). Gs-Rb1 up-regulated Atg4B, Atg5, Beclin-1, Atg7, LC3B II, the LC3B II/I ratio and cathepsin B activity of hypoxia cardiomyocytes (P<0.05), each of these protein levels was significantly enhanced by Ara A (all P<0.01), but was not affected by AICAR (all P>0.05). Gs-Rb1 significantly down-regulated P62 levels of hypoxic cardiomyocytes (P<0.05). The P62 levels of hypoxic cardiomyocytes were inhibited by Ara A (P<0.05) and were not affected by AICAR (P=0.871). Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

Analyzing the anti-ischemia-reperfusion injury effects of ginsenoside Rb1 mediated through the inhibition of p38α MAPK.

Recent studies have demonstrated that ginsenoside Rb1 protects the myocardium from ischemia-reperfusion (I/R) injury. However, the precise mechanisms for this protection have not been determined. This study aimed to determine whether the attenuation of I/R-induced myocardial injury by ginsenoside Rb1 (GS Rb1) is due to inhibition of p38α mitogen-activated protein kinase (MAPK). Sprague-Dawley rats were distributed among 6 treatment groups: sham group; I/R group; p38 MAPK inhibitor SB203580 group (SB + I/R); GS Rb1 group (GS + I/R); p38 MAPK agonist anisomycin group (Ani + I/R); and the GS Rb1 + Ani group (GS + Ani + I/R). All of the anaesthetized rats, except those in the sham group, underwent an open-chest procedure that involved 30 min of myocardial ischemia followed by 2 h of reperfusion. Myocardial infarction size (MIS), caspase-3 activity, and levels of the cytokine tumor necrosis factor alpha (TNF-α) in the myocardium were monitored. The expressions of p38α MAPK, caspase-3, and TNF-α in the myocardium were assayed. GS Rb1 reduced MIS and attenuated caspase-3 activity and the levels of TNF-α in the myocardium. Protein expression of total p38α MAPK was not significantly altered. In the Ani + I/R and I/R groups, the levels of phospho-p38α MAPK were significantly increased compared with the sham group, and these increased levels were reduced with GS Rb1. Hemodynamic parameters were not significantly different between the GS + I/R and SB + I/R groups. GS Rb1 exerts an anti-apoptotic effect that protects against I/R injury by inhibiting p38α MAPK phosphorylation, suggesting that GS Rb1-mediated protection requires the inhibition of p38α MAPK.

Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes.

To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α (Hif-1α). Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group, a simple CoCl group, a simple Gs-Rb1 group, a CoCl and Gs-Rb1 hypoxia group, a CoCl and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) group, a CoCl and YC-1 group and a Gs-Rb1 group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl, Gs-Rb1 and YC-1 was 500 μmol/L, 200 μmol/L and 5 μmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1α were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction (RT-PCR). (1) The anti-apoptosis effect of Gs-Rb1 on hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ, including mRNA and protein), a positive correlation between apelin (or APJ) protein and Hif-1a protein, in hypoxia cardiomyocytes. The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.

GW24-e2242 Effects of Ginsenoside-Rbl improving nuclear factor kappa B system in rats with chronic heart failure induced by adriamycin

ObjectivesBasing on the adriamycin-induced chronic heart failure (CHF), the present study elucidated whether the effect of Ginsenosides-Rbl (Gs-Rb1) improving cardiac function was performed by inhibiting nuclear factor kappa B (NF-κB),...

GW24-e0757 Ginsenosides-Rbl improves adriamycin-induced heart failure by adjusting the protein kinase R-like ER kinase pathway

ObjectivesBasing on the adriamycin-induced heart failure (HF), the present study elucidated whether the effect of Ginsenosides-Rbl (Gs-Rb1) improving cardiac function was performed by inhibiting protein kinase R-like ER kinase (PERK)...

GW24-e2244 Ginsenosides-Rbl improves adriamycin-induced heart failure by adjusting connexin 43

ObjectivesOn the basis of adriamycin (Adr)-induced heart failure (HF), the present study elucidated whether the effect of Ginsenosides-Rbl (Gs-Rb1), improving cardiac function, was performed by connexin 43 (CX43) and other...

GW24-e0755 Suppression of local inflammation contributes to the heart-protective effect of ginsenoside Rb1 in rats with heart failure

ObjectivesChronic inflammation have emerged as important role in heart failure (HF). However, suppressing local inflammatory effect of ginsenoside Rb1 (Gs-Rb1) in HF remains to be elucidated. Thus, the present study...

GW24-e2243 Effects of Ginsenoside-Rbl on protein kinase C system in rats hypertrophic cardiomyocytes mediated by endothelin 1 ex vivo

ObjectivesOn the basis of hypertrophic cardiomyocytes induced by endothelin 1 (ET-1), the present study aimed at investigating whether the effects of Ginsenosides-Rbl (Gs-Rb1) inhibiting cardiomyocyte hypertrophy were mediated by protein...

Effects of Ginsenosides-Rbl inhibiting cardiomyocyte hypertrophy via NHE-1-dependent calcineurin activation ex vivo

ObjectivesGinsenosides-Rbl (Gs-Rbl), a main component of Ginsenosides extracted from Ginseng, is a type of activity element playing a therapeutic role in the cardiovascular system. The present study aimed at determining...

Ginsenosides-Rbl exerts beneficial effects on left ventricular dysfunction and remodelling early after myocardial infarction

ObjectivesThe aim of this study was to investigate whether Ginsenosides-Rbl (Gs-Rb1) has improved left ventricular (LV) dysfunction and remodelling early after myocardial infarction (MI).MethodsSixty male 8-week-old Wistar mice with extensive...

E0045 Effects of Ginsenoside-Rbl on aldosterone-induced elastin production in rat cardiac fibroblasts ex vivo

ObjectiveTo investigate whether the role of Ginsenosides-Rbl (Gs-Rb1) on aldosterone-induced elastic fibre deposition of neonatal rat cardiac fibroblasts (CFs) in vitro.MethodsCFs were randomly divided into control group, aldosterone group (10...

Ginsenoside Rb1 protects cardiomyocytes against CoCl2-induced apoptosis in neonatal rats by inhibiting mitochondria permeability transition pore opening

To investigate whether mitochondria permeability transition pore (mPTP) opening was involved in ginsenoside Rb1 (Gs-Rb1) induced anti-hypoxia effects in neonatal rat cardiomyocytes ex vivo. Cardiomyocytes were randomly divided into 7 groups: control group, hypoxia group (500 micromol/L CoCl(2)), Gs-Rb1 200 micromol/L group (CoCl(2) intervention+Gs-Rb1), wortmannin (PI3K inhibitor) 0.5 micromol/L group, wortmannin+Gs-Rb1 group, adenine 9-beta-D-arabinofuranoside (Ara A, AMPK inhibitor) 500 micromol/L group, and Ara A and Gs-Rb1 group. Apoptosis rate was determined by using flow cytometry. The opening of the transient mPTP was assessed by using co-loading with calcein AM and CoCl(2) in high conductance mode. Expression of GSK-3beta, cytochrome c, caspase-3 and poly (ADP-ribose) polymerase (PARP) was measured by using Western blotting. DeltaGSK-3beta was defined as the ratio of p-Ser9-GSK-3beta to total GSK-3beta. CoCl(2) significantly stimulated mPTP opening and up-regulated the level of DeltaGSK-3beta. There was a statistically significant positive correlation between apoptosis rate and mPTP opening, between apoptosis rate and DeltaGSK-3beta, and between mPTP opening and DeltaGSK-3beta. Gs-Rb1 significantly inhibited mPTP opening induced by hypoxia (41.3%+/-2.0%, P<0.001) . Gs-Rb1 caused a 77.3%+/-3.2% reduction in the expression of GSK-3beta protein (P<0.001) and a significant increase of 1.182+/-0.007-fold (P=0.0001) in p-Ser9-GSK-3beta compared with control group. Wortmannin and Ara A significantly inhibited the effect of Gs-Rb1 on mPTP opening and DeltaGSK-3beta. Gs-Rb1 significantly decreased expression of cytochrome c (66.1%+/-1.7%, P=0.001), caspase-3 (56.5%+/-2.7%, P=0.001) and cleaved poly ADP-ribose polymerase (PARP) (57.9%+/-1.4%, P=0.001). Gs-Rb1 exerted anti-hypoxia effect on neonatal rat cardiomyocytes by inhibiting GSK-3beta-mediated mPTP opening.

Cost effectiveness of antenatal screening for cystic fibrosis

To estimate the cost effectiveness of different antenatal screening programmes for cystic fibrosis. Antenatal clinics and general practices in the United Kingdom. Four components of the screening process were identified: information giving, DNA testing, genetic counselling, and prenatal diagnosis. The component costs were derived from the literature and from a pilot screening study in Yorkshire. The cost of a given screening programme was then obtained by summing the components according to the specific screening strategy adopted (sequential and couple), the proportion of carriers detected by the DNA test, and the uptake of screening. Baseline assumptions were made about the proportion with missing information on carrier status from previous pregnancies (20%), the proportion changing partners between pregnancies (20%), and the uptake of prenatal diagnosis (100%). Sensitivity analysis was performed by varying these assumptions. Cost per affected pregnancy detected. Under the baseline assumptions sequential screening costs between pounds 40,000 and pounds 90,000 per affected pregnancy detected, depending on the carrier detection rate and uptake. Couple screening was more expensive, ranging from pounds 46,000 to pounds 104,000. From the sensitivity analysis a 10% change in the assumed proportion with missing information from a previous pregnancy alters the cost by pounds 4000; a 10% change in the proportion with new partners has a similar effect but only for couple screening; and cost will change directly in proportion to the uptake of prenatal diagnosis. While economic analysis cannot determine screening policy, the paper provides the NHS with the information on cost effectiveness needed to inform decisions on the introduction of a screening service for cystic fibrosis.