Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still...

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Main Authors: Jingui Hu, Ling Zhang, Fei Fu, Qiong Lai, Lu Zhang, Tao Liu, Boyang Yu, Junping Kou, Fang Li
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:Journal of Ginseng Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845321001032
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author Jingui Hu
Ling Zhang
Fei Fu
Qiong Lai
Lu Zhang
Tao Liu
Boyang Yu
Junping Kou
Fang Li
author_facet Jingui Hu
Ling Zhang
Fei Fu
Qiong Lai
Lu Zhang
Tao Liu
Boyang Yu
Junping Kou
Fang Li
author_sort Jingui Hu
collection DOAJ
description Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.
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spelling doaj.art-9a3d691e5b324b62adcaf3793a31d4442022-12-21T19:17:55ZengElsevierJournal of Ginseng Research1226-84532022-03-01462255265Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagyJingui Hu0Ling Zhang1Fei Fu2Qiong Lai3Lu Zhang4Tao Liu5Boyang Yu6Junping Kou7Fang Li8Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaCorresponding author. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China.; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaCorresponding author. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China.; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaBackground: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.http://www.sciencedirect.com/science/article/pii/S1226845321001032Acute myocardial ischemiaAMPKGinsenoside Rb1MetabolomicsMitophagy
spellingShingle Jingui Hu
Ling Zhang
Fei Fu
Qiong Lai
Lu Zhang
Tao Liu
Boyang Yu
Junping Kou
Fang Li
Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
Journal of Ginseng Research
Acute myocardial ischemia
AMPK
Ginsenoside Rb1
Metabolomics
Mitophagy
title Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
title_full Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
title_fullStr Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
title_full_unstemmed Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
title_short Cardioprotective effect of ginsenoside Rb1 via regulating metabolomics profiling and AMP-activated protein kinase-dependent mitophagy
title_sort cardioprotective effect of ginsenoside rb1 via regulating metabolomics profiling and amp activated protein kinase dependent mitophagy
topic Acute myocardial ischemia
AMPK
Ginsenoside Rb1
Metabolomics
Mitophagy
url http://www.sciencedirect.com/science/article/pii/S1226845321001032
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