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AIM: To elucidate the effect of ginsenoside Rb1 (Gs-Rb1) on the glucose metabolism to improve the viability of the cardiomyocytes under hypoxia, and whether hypoxia-inducible factor 1α(HIF-1α) and/or AMPKαare involved in the process.METHODS: The neonatal rat cardiomyocytes were cultured, and randomly divided into control group, hypoxia (1% O2 , 94% N2 and 5% CO2 ) group, Gs-Rb1 (200 μmol/L) group, Ara-A (500 μmol/L) group, Gs-Rb1 +Ara-A group, YC-1 (5 μmol/L) group, Gs-Rb1 +YC-1 group, Ara-A +YC-1 group and Gs-Rb1 +YC-1 +Ara-A group.After the intervention for 8 h, the cell viability was analyzed by MTT assay.The protein levels of AMPK, HIF-1αand glucose transporter-4 (GLUT-4) were determined by Western blot.The activities of heterophosphatase (HK), phos-phofructokinase (PFK) and lactic dehydrogenase (LDH) were measured by ELISA.RESULTS: Gs-Rb1 significantly im-proved the viability of hypoxic cardiomyocytes, which was significantly inhibited by YC-1 and Ara-A.In addition, YC-1 and Ara-A had a synergistic effect.Gs-Rb1 increased the protein levels of AMPK and HIF-1αin the hypoxic cardiomyo-cytes, which was significantly inhibited by Ara-A and YC-1.Gs-Rb1 significantly increased the expression of GLUT-4 on the cytomembrane of hypoxic cardiomyocytes, which was significantly inhibited by YC-1 or Ara-A, especially Ara-A +YC-1.Gs-Rb1 significantly increased the activities of HK, PFK and LDH, all those were significantly inhibited by YC-1 or Ara-A.Besides, YC-1 and Ara-A had a synergistic effect.CONCLUSION: Gs-Rb1 improves the viability of hypoxic car-diomyocytes, which may be related to the regulation of glucose uptake and enhancement of glycolysis by synergy of both HIF-1αand AMPK.
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Objective: To explore whether relieving effect of Ginsenosides-Rb1 (Gs-Rb1) on chronic heart failure (CHF) induced by adriamycin is related to improving levels of tumor necrosis factor (TNF) receptor (TNFR) and ligand TNF-α or not. Methods: Adriamycin-induced CHF model rats were randomly divided into adriamycin group (n=15, received adriamycin 1 μmol/L) and Gs-Rb1 group (n=17, received Gs-Rb1 70 mg•kg-1•d-1 based on adriamycin group), another 10 healthy Wistar rats were selected as normal control group. Meanwhile, cultured cardiomyocytes of neonatal rats were accordingly divided into normal control group, adriamycin group and adriamycin+Gs-Rb1 group. After intervention, echocardiography, levels of TNFR/TNF-α mRNA and protein were measured and compared among three groups. Results: 1. In vivo: Compared with normal control group TNFR-1 [protein（0.13±0.02）kDa, mRNA（0.19±0.05）bp]，TNFR-2[protein（0.24±0.01）kDa, mRNA（0.13±0.02）bp]，TNF-α [protein（0.11±0.01）kDa, mRNA（0.26±0.05）bp], the levels of TNFR-1 [protein（0.67±0.04）kDa,（0.51±0.04）kDa；mRNA（0.81±0.03）bp，（0.49±0.05）bp]，TNFR-2 [protein（0.61±0.05）kDa, （0.47±0.03）kDa，mRNA（0.28±0.03）bp，（0.18±0.04）bp] and TNF-α [protein（0.28±0.04）kDa, （0.20±0.03）kDa， mRNA（0.67±0.05）bp，（0.45±0.04）bp] significantly rose（P<0.05 or <0.01） in adriamycin group and Gs-Rb1 group; and those levels of TNFR-1, TNFR-2, TNF-α protein and mRNA of Gs-Rbl group were significant reduction than those of adriamycin group; 2. In vitro: The results were similar, those of adriamycin group and Gs-Rb1 group were also significant rise than those of normal control group（P<0.05 or <0.01），those of Gs-Rbl group were significant reduction than those of adriamycin group（P<0.05 or <0.01）. Conclusion: TNFR/TNF-α expression may play a certain role in the process of adriamycin-induced CHF; improving effect of Gs-Rb1 on adriamycin-induced CHF may be related to regulation of TNFR/TNF-α.
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Objective:To explore whether ginsenosides-Rb1 (Gs-Rb1)can relieve cardiomyocyte hypertrophy induced by endothelin-1 (ET-1)via protein kinase C (PKC)system.Methods:Cardiomyocytes of neonatal rat were random-ly divided into blank control group,Gs-Rb1 group,ET-1 group,Gs-Rb1+ET-1 group,ET-1+CHE (chelerythrine, PKC blocker)group and Gs-Rb1 +ET-1 +CHE group.After 96h intervention,cardiomyocyte surface area,total protein content,PKC activity,c-fos and p-c-jun expressions were measured.Results: (1)Cardiomyocyte surface area and total protein content in Gs-Rb1+ET-1 group were significantly lower than those of ET-1 group (P <0.05~<0.001),but not significant different with those of Gs-Rb1+ET-1+CHE group,P =0.569;(2)PKC activity in Gs-Rb1+ET-1 group was significantly lower than that of ET-1 group [(9.3±0.6)pmol·min-1 ·mg-1 vs.(14.1± 0.9)pmol·min-1 ·mg-1 ],but significantly higher than that of Gs-Rb1+ET-1+CHE group [(2.7±0.2)pmol· min-1 ·mg-1 ],P <0.001 all;(3)Expressions of c-fos and p-c-jun gene and protein in ET-1 group were significant-ly higher than those of blank control group (P <0.001 all);compared with ET-1 group,there were significant re-ductions in expressions of c-fos [mRNA/protein:(0.53±0.05/0.39±0.02)vs.(0.43±0.03/0.31±0.03)]and p-c-jun [mRNA/protein:(0.64±0.04/0.44±0.02)vs.(0.33±0.05/0.37±0.03)]in Gs-Rb1+ET-1 group and ex-pressions of c-fos [mRNA/protein:0.41 ± 0.05/0.31 ± 0.02]and p-c-jun [mRNA/protein:0.31 ± 0.05/0.36 ±0.03]in ET-1+CHE group (P <0.05 or <0.001),expressions of c-fos and p-c-jun gene and protein in Gs-Rb1+ET-1+CHE group were significantly lower than those of Gs-Rb1+ET-1 group and ET-1+CHE group (P <0.05 or<0.001).Conclusion:Gs-Rb1 can significantly inhibit cardiomyocyte hypertrophy induced by ET-1 and PKC system is one of pathways mediating this biological effect.
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Objective:To explore whether the effect relieving chronic heart failure (CHF) induced by Adriamycin of Ginsenoside-Rbl (Gs-Rbl ) is related to inhibiting Toll-like receptor (TLR ) . Methods :Adriamycin-induced CHF model rats were randomly divided into Adriamycin group (n=15) and Gs-Rb1 group (70 mg/kg d ,n=17);another 10 normal rats were regard as control group .Neonate rat cardiomyocytes were also randomly divided into control group ,Adriamycin group (1 μmol/L) and Gs-Rb1 group (1 μmol/L Adriamycin + 200 μmol/L Gs-Rbl) .After the intervention being performed ,echocardiography and expressions of TLR2/TLR4 gene and protein were assessed in all groups .Results:(1) Both studies in vivo and in vitro indicated that expressions of TLR 2 protein and mRNA in Adriamycin group were significantly higher than those of control group ,compared with Adriamycin group ,there were significant reductions in expressions of TLR2 protein [ (0.975 ± 0.022/0.564 ± 0.031) vs .(0.593 ± 0.018/0.344 ± 0.024)] and mRNA [ (0.576 ± 0.029/0.853 ± 0.043) vs .(0.349 ± 0.015/0.401 ± 0.021)] in Gs-Rbl group ,P<0.01 both ;(2) No matter study in vivo or in vitro ,expressions of TLR4 protein and mRNA in Adriamy-cin group were significantly higher than those of control group ,compared with Adriamycin group ,there were signif-icant reductions in expressions of TRL4 protein [ (0.654 ± 0.032/0.519 ± 0.013 ) vs . (0.371 ± 0.013/0.254 ± 0.027)] and mRNA [ (1.602 ± 0.013/0.838 ± 0.021) vs .(1.140 ± 0.021/0.503 ± 0.022)] in Gs-Rbl group , P<0.01 both .Conclusion:Adriamycin may trigger the process of CHF through increasing TLR 2 and TLR4. The effect of Gs-Rbl improving adriamycin-induced CHF may be related to inhibition of TLR 2 and TLR4 .
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Objective To investigate the effect of ginsenosides-Rb1(Gs-Rb1) on doxorubicin (Dox)-induced heart failure (HF), and the related mechanisms of connexin 43 (CX43) thereof. Methods Rats with Dox-induced HF were ran-domly divided into Dox group (n=15) and Gs-Rb1 group (n=17), and the health age-matched rats were as control (n=15). In addition, cardiomyocytes were randomly divided into Dox group, Gs-Rb1 group and control group. After the intervention, echocardiography or apoptotic ratio (AR) was analyzed, respectively. The expression levels of p21-activated kinase 1 (PAK1), protein phosphatase type 2A (PP2A) and CX43 were detected by Western bolt or RT-PCR analysis, respectively. Re-sults Gs-Rb1 significantly improved heart function in rats with HF, decreased left ventricular mass index and inhibited the cell apoptosis induced by Dox. Both mRNA and protein expressions of CX43 were significantly decreased in Dox group than those of control group. The expression of CX43 was significantly increased in Gs-Rb1 group, which was significantly lower than that of control group. There was no significant difference in PAK1 between Dox group and control group (P>0.05). The expression of PAK1 was significantly up-regulated by Gs-Rb1. The PP2A protein was significantly up-regulated in Dox group than that of control group, which was significantly higher in Gs-Rb1 group than that of Dox group. Conclusion Gs-Rb1 improved HF by adjusting CX43, which may be mediated by PAK1-PP2A.