The Experts below are selected from a list of 1776 Experts worldwide ranked by ideXlab platform
Qi-zhu Tang - One of the best experts on this subject based on the ideXlab platform.
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Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress
Oxidative medicine and cellular longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against myocardial infarction induced cardiac remodeling via nnos no regulated oxidative stress
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.
British journal of pharmacology, 2018Co-Authors: Yang Xiao, Zheng Yang, Ming Xia Duan, Yuan Yuan, Hai Han Liao, Xiao-han Jiang, Wei Deng, Qi-zhu TangAbstract:BACKGROUND AND PURPOSE Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of Aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with Aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then Aucubin (1 or 5 mg·kg-1 body weight day-1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. KEY RESULTS Aucubin effectively suppressed cardiac remodelling; in mice, Aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of Aucubin. Blocking or knocking down the β3 -adrenoceptor abolished the protective effects of Aucubin in vitro. Furthermore, Aucubin enhanced the protective effects of a β3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of Aucubin. CONCLUSIONS AND IMPLICATIONS Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β3 -adrenoceptor/AC/cAMP pathway. These findings suggest that Aucubin could have potential as a treatment for cardiac remodelling and heart failure.
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Aucubin protects against tgfβ1 induced cardiac fibroblasts activation by mediating the ampkα mtor signaling pathway
Planta Medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
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Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway.
Planta medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
Yang Xiao - One of the best experts on this subject based on the ideXlab platform.
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Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress
Oxidative medicine and cellular longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against myocardial infarction induced cardiac remodeling via nnos no regulated oxidative stress
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.
British journal of pharmacology, 2018Co-Authors: Yang Xiao, Zheng Yang, Ming Xia Duan, Yuan Yuan, Hai Han Liao, Xiao-han Jiang, Wei Deng, Qi-zhu TangAbstract:BACKGROUND AND PURPOSE Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of Aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with Aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then Aucubin (1 or 5 mg·kg-1 body weight day-1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. KEY RESULTS Aucubin effectively suppressed cardiac remodelling; in mice, Aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of Aucubin. Blocking or knocking down the β3 -adrenoceptor abolished the protective effects of Aucubin in vitro. Furthermore, Aucubin enhanced the protective effects of a β3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of Aucubin. CONCLUSIONS AND IMPLICATIONS Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β3 -adrenoceptor/AC/cAMP pathway. These findings suggest that Aucubin could have potential as a treatment for cardiac remodelling and heart failure.
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Aucubin protects against tgfβ1 induced cardiac fibroblasts activation by mediating the ampkα mtor signaling pathway
Planta Medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
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Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway.
Planta medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
Ming Xia Duan - One of the best experts on this subject based on the ideXlab platform.
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Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress
Oxidative medicine and cellular longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against myocardial infarction induced cardiac remodeling via nnos no regulated oxidative stress
Oxidative Medicine and Cellular Longevity, 2018Co-Authors: Zheng Yang, Yang Xiao, Ming Xia Duan, Chen Liu, Yuan Yuan, Yan-yan Meng, Hai Han Liao, Qi-zhu TangAbstract:Whether Aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with Aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the Aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, Aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that Aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo Aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of Aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of Aucubin on cardiac remodeling. Taken together, Aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
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Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.
British journal of pharmacology, 2018Co-Authors: Yang Xiao, Zheng Yang, Ming Xia Duan, Yuan Yuan, Hai Han Liao, Xiao-han Jiang, Wei Deng, Qi-zhu TangAbstract:BACKGROUND AND PURPOSE Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of Aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with Aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then Aucubin (1 or 5 mg·kg-1 body weight day-1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. KEY RESULTS Aucubin effectively suppressed cardiac remodelling; in mice, Aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of Aucubin. Blocking or knocking down the β3 -adrenoceptor abolished the protective effects of Aucubin in vitro. Furthermore, Aucubin enhanced the protective effects of a β3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of Aucubin. CONCLUSIONS AND IMPLICATIONS Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β3 -adrenoceptor/AC/cAMP pathway. These findings suggest that Aucubin could have potential as a treatment for cardiac remodelling and heart failure.
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Aucubin protects against tgfβ1 induced cardiac fibroblasts activation by mediating the ampkα mtor signaling pathway
Planta Medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
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Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway.
Planta medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
Xiao-han Jiang - One of the best experts on this subject based on the ideXlab platform.
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Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.
British journal of pharmacology, 2018Co-Authors: Yang Xiao, Zheng Yang, Ming Xia Duan, Yuan Yuan, Hai Han Liao, Xiao-han Jiang, Wei Deng, Qi-zhu TangAbstract:BACKGROUND AND PURPOSE Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of Aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with Aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then Aucubin (1 or 5 mg·kg-1 body weight day-1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. KEY RESULTS Aucubin effectively suppressed cardiac remodelling; in mice, Aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of Aucubin. Blocking or knocking down the β3 -adrenoceptor abolished the protective effects of Aucubin in vitro. Furthermore, Aucubin enhanced the protective effects of a β3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of Aucubin. CONCLUSIONS AND IMPLICATIONS Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β3 -adrenoceptor/AC/cAMP pathway. These findings suggest that Aucubin could have potential as a treatment for cardiac remodelling and heart failure.
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Aucubin protects against tgfβ1 induced cardiac fibroblasts activation by mediating the ampkα mtor signaling pathway
Planta Medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
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Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway.
Planta medica, 2017Co-Authors: Yang Xiao, Ming Xia Duan, Xiao-han Jiang, Wei Chang, Ya-ge Jin, Qi-zhu TangAbstract:Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid Aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with Aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of Aucubin. As a result, Aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, Aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that Aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.
Liji Jin - One of the best experts on this subject based on the ideXlab platform.
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Neuroprotective properties of Aucubin in diabetic rats and diabetic encephalopathy rats.
Molecular biology reports, 2012Co-Authors: Hongyu Xue, Gui-zhen Gao, Xue Mei Fang, Liji JinAbstract:In this study, we determined the neuroprotective effect of Aucubin on diabetes and diabetic encephalopathy. With the exception of the control group, all rats received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes mellitus (DM). Aucubin (1, 5, 10 mg/kg ip) was used after induction of DM (immediately) and diabetic encephalopathy (65 days after the induction of diabetes). The diabetic encephalopathy treatment groups were divided into short-term and long-term treatment groups. Treatment responses to all parameters were examined (body weight, plasma glucose, Y-maze error rates and proportion of apoptotic cells). In diabetic rats, Aucubin controlled blood glucose levels effectively, prevented complications, and improved the quality of life of diabetic rats. In diabetic encephalopathy, Aucubin significantly rescued neurons in the hippocampal CA1 subfield and reduced working errors during behavioral testing. The significant neuroprotective effect of Aucubin could be seen not only in the short term (15 days) but also in the long term (45 days), which was a highly encouraging finding. These data suggest that Aucubin may be a potential neuroprotective agent.
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protective effects of Aucubin on h2o2 induced apoptosis in pc12 cells
Phytotherapy Research, 2012Co-Authors: Hongyu Xue, Gui-zhen Gao, Qiu-ye Lin, Liji JinAbstract:The present study investigated the neuroprotective effects of Aucubin on hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells. Exposure of PC12 cells to 0.25 mm H2O2 induced a leakage of lactate dehydrogenase and decreased cell viability, as shown by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. In a dose over 0.1 mm, Aucubin increased PC12 cellular viability and markedly attenuated H2O2-induced apoptotic cell death. Quantitation of apoptosis by flow cytometry indicated that Aucubin inhibited H2O2-induced apoptosis in PC12 cells. Nuclear damage was alleviated by Aucubin, as shown by Hoechst staining. In addition, the levels of malondialdehyde were reduced and the activity of superoxide dismutase, catalase and glutathione peroxidase was augmented in these cells. These results indicated that Aucubin inhibited H2O2-induced apoptosis in PC12 cells through regulation of the endogenous oxidant–antioxidant balance. Our results suggest that Aucubin is a potential protective agent for the treatment of oxidative-stress-induced neurodegenerative disease. Copyright © 2011 John Wiley & Sons, Ltd.
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Protective Effects of Aucubin on H2O2‐Induced Apoptosis in PC12 Cells
Phytotherapy research : PTR, 2011Co-Authors: Hongyu Xue, Gui-zhen Gao, Qiu-ye Lin, Liji JinAbstract:The present study investigated the neuroprotective effects of Aucubin on hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells. Exposure of PC12 cells to 0.25 mm H2O2 induced a leakage of lactate dehydrogenase and decreased cell viability, as shown by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. In a dose over 0.1 mm, Aucubin increased PC12 cellular viability and markedly attenuated H2O2-induced apoptotic cell death. Quantitation of apoptosis by flow cytometry indicated that Aucubin inhibited H2O2-induced apoptosis in PC12 cells. Nuclear damage was alleviated by Aucubin, as shown by Hoechst staining. In addition, the levels of malondialdehyde were reduced and the activity of superoxide dismutase, catalase and glutathione peroxidase was augmented in these cells. These results indicated that Aucubin inhibited H2O2-induced apoptosis in PC12 cells through regulation of the endogenous oxidant–antioxidant balance. Our results suggest that Aucubin is a potential protective agent for the treatment of oxidative-stress-induced neurodegenerative disease. Copyright © 2011 John Wiley & Sons, Ltd.
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Aucubin modulates Bcl-2 family proteins expression and inhibits caspases cascade in H2O2-induced PC12 cells
Molecular biology reports, 2010Co-Authors: Hongyu Xue, Gui-zhen Gao, Qiu-ye Lin, Dong Yan Niu, Liji JinAbstract:In this study, the effect of Aucubin on H(2)O(2)-induced apoptosis was studied by using a rat pheochromocytoma (PC12) cell line. We have analyzed the apoptosis of H(2)O(2)-induced PC12 cells, H(2)O(2)-induced apoptosis appeared to correlate with lower Bcl-2 expression, higher Bax expression and sequential activation of caspase-3 leading to cleavage of poly-ADP-ribose polymerase (PARP). Aucubin not only inhibited lower Bcl-2 expression, high Bax expression, but also modulated caspase-3 activation, PARP cleavage, and eventually protected against H(2)O(2)-induced apoptosis. These results indicated that Aucubin can obstruct H(2)O(2)-induced apoptosis by regulating of the expression of Bcl-2 and Bax, as well as suppression of caspases cascade activation.
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Aucubin prevents loss of hippocampal neurons and regulates antioxidative activity in diabetic encephalopathy rats.
Phytotherapy research : PTR, 2009Co-Authors: Hongyu Xue, Liji Jin, Lei Jin, Peng Zhang, Yan-qiu XiaAbstract:In this study, the neuroprotection of Aucubin and its mechanism were evaluated in the rat model of diabetic encephalopathy. Diabetes mellitus (DM) rats were stratified by cognitive capability (CC), and assigned to four treatment groups for Aucubin treatment (doses of 0, 1, 5 or 10 mg/kg Aucubin), with a further two groups of non-DM rats ranked by CC as controls for Aucubin (doses of 0 or 5 mg/kg Aucubin). Neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in a Y-maze. The surviving neurons in CA1-CA4 and subiculum (SC) of the hippocampus were counted under a microscope. In addition, the apoptotic neurons in the CA1 of the hippocampus were also examined by using TUNEL staining. In order to clarify the mechanism of Aucubin's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase (NOS) together with the content of lipid peroxide in the hippocampus were assayed. The results proved that Aucubin significantly reduced the content of lipid peroxide, regulated the activities of antioxidant enzymatic and decreased the activity of NOS. All these effects indicated that Aucubin was a potential neuroprotective agent and its neuroprotective effects were achieved, at least in part, by promoting endogenous antioxidant enzymatic activities.
