Ginsenoside Rb1 Alleviates Oxidative Low-Density Lipoprotein–Induced Vascular Endothelium Senescence via the SIRT1/Beclin-1/Autophagy Axis

Shi, Guangyao; Liu, Dinghui; Zhou, Bin; Liu, Yong; Hao, Baoshun; Yu, Sungwook; Wu, Lin; Wang, Min; Song, Zhiming; Wu, Chaodong; Zhu, Jin; Qian, Xiaoxian

doi:10.1097/fjc.0000000000000775

Cited by 30 publications

(21 citation statements)

References 48 publications

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“…OxLDL is a commonly used inducer of endothelial cell senescence. In this regard, ginsenoside Rb1 exerts protection against endothelial cell senescence through the SIRT1/Beclin-1/autophagy axis ( 67 ). In addition, GW9508, an agonist of GPR120, has been shown to improve oxLDL-induced cell cycle arrest.…”

Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

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Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.

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Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

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“…Ginsenosides are the main active ingredients of Panax ginseng , a famous medicine known as the “King of Herbs” in Asian countries, and are mainly responsible for therapeutic and pharmacologic properties against cardiovascular and neurological disorders. − It reported that multiple ginsenosides were found to activate SIRT1, including ginsenosides Rc, Rb2, F1, and Rg1, − against oxidative damage, senescence, , cancer, inflammation, and metabolic diseases . Among the ginsenosides, ginsenoside Rc was reported to target mitochondrial functions, including free-radical scavenging, ATP content enhancement, and oxygen consumption recovery. , However, to our knowledge, how ginsenoside Rc interacts with SIRT1 to regulate glucose oxidation and mitochondrial biosynthesis in cardiomyocytes and neurons under physiological or I/R-injured conditions has not been clearly investigated.…”

Section: Introductionmentioning

confidence: 99%

A SIRT1 Activator, Ginsenoside Rc, Promotes Energy Metabolism in Cardiomyocytes and Neurons

Huang¹,

Su²,

Qi³

et al. 2021

J. Am. Chem. Soc.

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Targeting SIRT1 signaling pathway could improve glucose aerobic metabolism and mitochondrial biosynthesis to resist cardiac and neurological injuries. Ginsenoside Rc has been identified for targeting mitochondrial function, but how ginsenoside Rc interacts with SIRT1 to regulate energy metabolism in cardiomyocytes and neurons under physiological or ischemia/reperfusion (I/R)-injured conditions has not been clearly investigated. Here, we confirm the interaction of Rc on the residue sites of SIRT1 in promoting its activity. Ginsenoside Rc significantly promotes mitochondrial biogenesis and increases the levels of electron-transport chain complex II–IV in cardiomyocytes and neurons. Meanwhile, ginsenoside Rc pretreatment increases ATP production, glucose uptake, and the levels of hexokinase I/II and mitochondrial pyruvate carrier I/II in both cell models. In addition, ginsenoside Rc activates the PGC1α pathway to induce mitochondrial biosynthesis. More importantly, ginsenoside Rc reduces mitochondrial damage and apoptosis through SIRT1 restoration-mediated reduction of PGC1α acetylation in the I/R-induced cardiac and neuronal models. Collectively, the in vitro and in vivo data indicate that ginsenoside Rc as a SIRT1 activator promotes energy metabolism to improve cardio- and neuroprotective functions under normal and I/R injury conditions, which provides new insights into the molecular mechanism of ginsenoside Rc as a protective agent.

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“…Macrophages form cholesterol-rich foam cells by phagocytosing oxidized LDLs, which is the main factor for atherosclerotic lesions. In vitro, Rb 1 can alleviate ox-LDL-induced vascular endothelium senescence via the SIRT1/Beclin-1/autophagy axis [ 71 ]. Macrophages can differentiate into two antagonistic subtypes: M1 and M2, of which pro-inflammatory M1 macrophages can lead to a more vulnerable plaque, whereas anti-inflammatory M2 macrophages have protective effects.…”

Section: Cardiovascular Systemmentioning

confidence: 99%

Recent progress (2015–2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer

Lin

Xie

Zhong

et al. 2022

Journal of Ginseng Research

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Ginsenoside Rb 1 (Rb 1 ), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb 1 against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb 1 on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb 1 and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb 1 and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb 1 and its clinical applications.

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Ginsenoside Rb1 Alleviates Oxidative Low-Density Lipoprotein–Induced Vascular Endothelium Senescence via the SIRT1/Beclin-1/Autophagy Axis

Cited by 30 publications

References 48 publications

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

A SIRT1 Activator, Ginsenoside Rc, Promotes Energy Metabolism in Cardiomyocytes and Neurons

Recent progress (2015–2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer

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