Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis

Pharmacological Research, Journal Year: 2021, Volume and Issue: 168, P. 105599 - 105599

Published: April 7, 2021

Language: Английский

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Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

Biomolecules, Journal Year: 2020, Volume and Issue: 10(3), P. 444 - 444

Published: March 13, 2020

Panax ginseng, also known as Korean is a famous medicinal plant used for the treatment of many inflammatory diseases. Ginsenosides (ginseng saponins) are main class active constituents ginseng. The anti-inflammatory effects ginseng extracts were proven with purified ginsenosides, such ginsenosides Rb1, Rg1, Rg3, and Rh2, well compound K. negative regulation pro-inflammatory cytokine expressions (TNF-α, IL-1β, IL-6) enzyme (iNOS COX-2) was found mechanism in M1-polarized macrophages microglia. Recently, another action emerged explaining effect This pro-resolution inflammation derived by M2-polarized macrophages. Direct indirect evidence supports how several (ginsenoside Rg1) induce M2 polarization microglia, these cells contribute to suppression progression promotion resolution. In this review, new anti-inflammation summarized.

Language: Английский

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HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: March 12, 2022

Histone deacetylase 11 (HDAC11), a sole member of the class IV HDAC subfamily, participates in various cardiovascular diseases. Recent evidence showed that pyroptosis was form inflammatory programmed cell death and is critical for atherosclerosis (AS). However, little known about effect HDAC11 on endothelial AS. Thus, this study aims to investigate role vascular its molecular mechanism. Firstly, we found expression up-regulated occurred aorta ApoE-/- mice fed with high-fat diet (HFD) 8 or 12 weeks. Then, vitro treatment human umbilical vein cells (HUVECs) tumor necrosis factor-α (TNF-α) resulted pyroptosis, as evidenced by activation caspase-1 caspase-3 activation, cleavage downstream gasdermin D (GSDMD) E (GSDME/DFNA5), release pro-inflammatory cytokines interleukin (IL)-1β, IL-6 IL-18, well elevation LDH activity increase propidium iodide (PI)-positive cells. Besides, TNF-α increased induced via TNFR1 HUVECs. knockdown mitigated suppressing both NLRP3/caspase-1/GSDMD caspase-3/GSDME pathways TNF-α-induced Moreover, GSDME siRNA significantly decreased response, while disulfiram necrosulfonamide (NSA) further augmented inhibitory effects response. Further studies formed complex ERG acetylation levels ERG. More importantly, Taken together, our suggests might promote leading regulation Modulation may serve potential target therapeutic strategies

Language: Английский

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HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways

Biomolecules, Journal Year: 2019, Volume and Issue: 9(10), P. 512 - 512

Published: Sept. 20, 2019

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by ischemia reperfusion (I/R) injury. This process has particular significance for the treatment of patients. Notoginseng leaf triterpenes (PNGL), as valuable medicine, have been discovered to neuroprotective effects. However, it was not confirmed that whether PNGL may possess effects against I/R To explore their underlying mechanisms, middle artery occlusion/reperfusion (MCAO/R) model established. In vivo results suggested in MCAO/R rats, pretreatment (73.0, 146, 292 mg/kg) remarkably decreased infarct volume, reduced brain water content, improved neurological functions; moreover, significantly alleviated blood-brain barrier (BBB) disruption inhibited neuronal loss injury, while with different concertation (146, concentrations IL-6, TNF-α, IL-1 β, HMGB1 serums dose-dependent way, which indicated inflammation inhibition could be involved PNGL. The immunofluorescence western blot analysis showed expression, suppressed HMGB1-triggered inflammation, microglia activation (IBA1) hippocampus cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, ICAM-1 ischemic brains. Interestingly, administration (146 downregulated levels p-P44/42, p-JNK1/2 p-P38 MAPK, also expressions total NF-κB phosphorylated brains, downstream pathway triggered HMGB1. All these protective injury associated inhibiting suppressing MAPKs NF-κB, I/R-induced neuropathological changes. study offer insight into discovering new active compounds stroke.

Language: Английский

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Blueberry-Derived Exosome-Like Nanoparticles Counter the Response to TNF-α-Induced Change on Gene Expression in EA.hy926 Cells

Biomolecules, Journal Year: 2020, Volume and Issue: 10(5), P. 742 - 742

Published: May 10, 2020

Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary similar to mammalian exosomes have attracted attention for these features. In particular they appear be relevant the modulation several cellular processes well candidate carriers bioactive molecules (proteins, lipids, nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated uptake blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) ability B-ELNs modulate expression inflammatory genes response tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize dose-dependent manner; 2) pretreatment counters TNF-α-induced reactive oxygen species (ROS) generation loss viability modulates differential 29 (fold change > 1.5) induced TNF-α compared control; 3) pathway analysis reveals their involvement total 340 canonical pathways, 121 KEGG GO Biological processes; 4) intersection between differentially expressed (DE) miRNAs contained unveils set target genes, such prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), phosphodiesterase 7A (PDE7A), ELNs-contained cargo. conclusion, our study indicates can considered compounds potentially able protect vascular system against various stressors.

Language: Английский

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Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis

Journal of Ginseng Research, Journal Year: 2020, Volume and Issue: 45(1), P. 22 - 31

Published: July 16, 2020

Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in high rate death worldwide, with an increased prevalence age despite advances lifestyle management drug therapy. chronic progressive inflammatory process, mainly presents lipid accumulation, foam cell proliferation, response, atherosclerotic plaque formation rupture, thrombosis, vascular calcification. Therefore, there great need for reliable therapeutic drugs or remedies to cure alleviate atherosclerosis reduce the societal burden. Ginsenosides are natural steroid glycosides triterpene saponins obtained from plant ginseng. Several recent studies have reported that ginsenosides variety pharmacological activities against several including inflammation, cancer diseases. This review focuses on describing different functions underlying mechanisms various active (Rb1,-Rd, -F, -Rg1, -Rg2, -Rg3, compound K) atherosclerosis, which could provide useful insights developing novel effective anti-cardiovascular drugs.

Language: Английский

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Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 14

Published: Oct. 28, 2021

Yinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed investigate the active ingredients found in and find when treating using a combination network pharmacology, molecular docking, dynamics simulation approaches.The TCMSP database was obtain principle NCBI DisGeNet databases were main target genes involved intersectional targets obtained by EXCEL. We also Cytoscape 3.7.2 software construct "Traditional Chinese Medicine-Active Ingredient-Target" use STRING platform conduct "protein-protein interactional" (PPI) analyses on intersection targets. Bioconductor RX 64 4.0.0 then perform GO functional enrichment analysis KEGG pathway Molecular docking core protein-ligand interactions modeled AutoDock Vina software. A conducted for optimal Amber18 software.A total 63 powder, corresponding 175 targets, 508 hyperlipidemia 55 total. showed that key quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, artepillin A. The PPI proteins AKT1, IL6, VEGFA, PTGS2. enriched primarily response oxygen levels nutrient vesicular lumen associated with membrane rafts. These mainly AGE-RAGE (advanced glycation end products-receptor advanced products) signaling diabetic complications, fluid shear stress, atherosclerosis, as well other pathways. results indicated binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, PTGS2-taxifolin. Results from simulations PTGS2-taxifolin bound more stably, their free energies PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 -32.9 kcal/mol.This study based pharmacology reveals potential mechanisms treatment powder.

Language: Английский

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Oxidative Stress and Ginsenosides: An Update on the Molecular Mechanisms

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 15

Published: April 20, 2022

Ginsenosides are a class of active components extracted from ginseng plants (such as Panax ginseng, quinquefolium, and notoginseng). have significant protective effects on the nervous system, cardiovascular immune so they been widely used in treatment related diseases. Entry variety endogenous or exogenous harmful substances into body can lead to an imbalance between antioxidant defense system reactive oxygen species, thus producing toxic tissues cells. In addition, oxidative stress alter multiple signaling pathways, including Keap1/Nrf2/ARE, PI3K/AKT, Wnt/β-catenin, NF-κB pathways. With deepening research this field, various ginsenoside monomers reported exert through pathways good application prospects. This article summarized advancements regarding antioxidative mechanisms ginsenosides, providing theoretical basis for experimental clinical with ginsenosides.

Language: Английский

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Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 2, 2022

Panax ginseng and notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one most important active ingredients notoginseng. In last decades, more attention has focused on ginsenoside an antioxidative, anti-apoptotic anti-inflammatory agent that can protect nervous system. review, we summarize neuroprotective roles its potential mechanisms central system diseases (CNSDs), including neurodegenerative cerebral ischemia injury, depression spinal cord injury. conclusion, neuroprotection due to inhibition oxidative stress, apoptosis, neuroinflammation autophagy CNSDs may be promising candidate clinical future.

Language: Английский

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Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway

Phytomedicine, Journal Year: 2023, Volume and Issue: 119, P. 155002 - 155002

Published: Aug. 1, 2023

Language: Английский

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