Attenuation of TNF-α-Induced Inflammatory Injury in Endothelial Cells by Ginsenoside Rb1 via Inhibiting NF-κB, JNK and p38 Signaling Pathways

Zhou, Ping; Lu, Shan; Luo, Yun; Wang, Shan; Yang, Ke; Zhai, Yadong; Sun, Guibo

doi:10.3389/fphar.2017.00464

Cited by 127 publications

(82 citation statements)

References 44 publications

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“…We further demonstrate that Panx1 expression by cultured human vascular smooth muscle cells (SMC) is unaltered by TNF treatment ( Supplemental Figure 1D ). Previous studies have found TNF to reduce cell viability (Zhou et al, 2017). However, 24 hr TNF treatments ranging from 2.5-100 ng/mL for 24 hr did not alter HUVEC viability as measured by intracellular ATP levels, caspase-3 cleavage, or by cell morphology ( Supplemental Figure 1E-G ).…”

Section: Resultsmentioning

confidence: 98%

Endothelial pannexin 1 channels control inflammation by regulating intracellular calcium

Yang

DeLalio

Best

et al. 2019

Preprint

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25inflammation, endothelial cell, smooth muscle cell 4 to prolonged tumor necrosis factor alpha (TNF) treatment, Yang et al. found that the Panx1 5 channel is targeted to the plasma membrane, where it facilitates an increase in intracellular 6 calcium to control the production and release of cytokines including IL-1β. 7 8 GRAPHICAL ABSTRACT 9 10 Graphical Abstract: The inflammatory process in endothelial cells is controlled by Ca 2+ entry through Pannexin 1 membrane channels. 3 Abstract 1The proinflammatory cytokine IL-1β is a significant risk factor in cardiovascular disease 2 that can be targeted to reduce major cardiovascular events. IL-1β expression and release 3 are tightly controlled by changes in intracellular Ca 2+ . In addition, purinergic signaling 4 through ATP release has also been reported to promote IL-1β production. Despite this, 5 the mechanisms that control IL-1β synthesis and expression have not been identified. 6The pannexin 1 (Panx1) channel has canonically been implicated in ATP release, 7 especially during inflammation. However, resolution of purinergic signaling occurs quickly 8 due to blood flow and the presence of ectonucleotidases. We examined Panx1 in human 9 endothelial cells following treatment with the pro-inflammatory cytokine tumor necrosis 10 alpha (TNF). In response to long-term TNF treatment, we identified a dramatic increase 11 in Panx1 protein expression at the plasma membrane. Analysis by whole transcriptome 12 sequencing (RNA-seq), qPCR, and treatment with specific kinase inhibitors, revealed that 13 TNF signaling induced NFκβ-associated Panx1 transcription. Genetic inhibition of Panx1 14 reduced the expression and secretion of IL-1β. We initially hypothesized that increased 15Panx1-mediated ATP release acted in a paracrine fashion to control cytokine expression. 16However, our data demonstrate that IL1-β expression was not altered after direct ATP 17 stimulation, following degradation of ATP by apyrase, or after pharmacological blockade 18 of P2 receptors. These data suggest that non-purinergic pathways, involving Panx1, 19 control IL-1β production. Because Panx1 forms a large pore channel, we hypothesized it 20 may act to passively diffuse Ca 2+ into the cell upon opening to regulate IL-1β. High-21 throughput flow cytometric analysis demonstrated that TNF treatments lead to elevated 22 intracellular Ca 2+ . Genetic or pharmacological inhibition of Panx1 reduced TNF-23 associated increases in intracellular Ca 2+ , and IL-1β transcription. Furthermore, we found 24 that the Ca 2+ -sensitive NFκβ-p65 protein failed to localize to the nucleus after genetic or 25 pharmacological block of Panx1. Taken together, our study provides the first evidence 26 that intracellular Ca 2+ regulation via the Panx1 channel induces a feed-forward effect on 27NFκβ to regulate IL-1β synthesis and release in endothelium during inflammation. 28 4 (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates

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Section: Resultsmentioning

confidence: 98%

Endothelial pannexin 1 channels control inflammation by regulating intracellular calcium

Yang

DeLalio

Best

et al. 2019

Preprint

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“…Ginsenoside Rf showed an inhibitory effect on the inflammatory mediators downstream of p38/NF-κB activation, such as the reduction of IL-1β, IL-6, TNF-α, NO, and ROS productions, on TNF-α-stimulated HT-29 intestinal epithelial cells and RAW264.7 mouse macrophage cells [18]. Moreover, its anti-inflammatory activity, along with ginsenoside Rb1 and Rg1, was reported, and anti-oxidation and the inhibition of NO synthesis were proposed as its mechanism [19,20].…”

Section: Ginsenosides In Anti-inflammationmentioning

confidence: 94%

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

2020

Biomolecules

129

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

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“…Ginseng is a herb that has been used since years ago in Asian countries as it possesses various therapeutic benefits which come from its active compound called ginsenoside (Kim, Yi, Kim, & Cho, 2017;Nuri, Yee, Gupta, Khan, & Ming, 2016). Ginseng has appealing biological properties including the effects on CVDs such as anti-inflammatory, anti-oxidative, and protective toward human cell (Zhou et al, 2017). These abilities arose the chosen of ginseng to be applied in cardiovascular applications.…”

Section: Discussionmentioning

confidence: 99%

Effects of different polyaniline emeraldine compositions in electrodepositing ginsenoside encapsulated poly(lactic‐co‐glycolic acid) microcapsules coating: Physicochemical characterization and in vitro evaluation

Lukman

Saidin

2020

J Biomedical Materials Res

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Even though drug‐eluting stent (DES) has prominently reduced restenosis, however, its complication of delayed endothelialization has caused chronic side effect. A coating of ginseng‐based biodegradable polymer could address this issue due to its specific therapeutic values. However, deposition of this type of stable coating on metallic implant often scarce. Therefore, in this study, different polyaniline (PANI) emeraldine compositions were adopted to electrodeposit ginsenoside encapsulated poly(lactic‐co‐glycolic acid) microcapsules coating. The coating surfaces were analyzed using attenuated total reflectance‐Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, scanning electron microscopy, contact angle, and atomic force microscopy instruments. A month coating stability was then investigated with an evaluation of in vitro human umbilical vein endothelial cell analyses consisted of cytotoxicity and cells attachment assessments. The 1.5 mg PANI emeraldine has assisted the formation of stable, uniform, and rounded microcapsules coating with appropriate wettability and roughness. Less than 1.5 mg PANI emeraldine was not enough to drive the formation of microcapsules coating while greater than 1.5 mg caused the deposition of melted microcapsules. The similar coating also has promoted greater cells proliferation and attachment compared to other coating variation. Therefore, the utilization of electrodeposition to deposit a drug‐based polymer coating could be implemented to develop DES, in accordance to stent implantation which ultimately aims for enrich endothelialization.

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Attenuation of TNF-α-Induced Inflammatory Injury in Endothelial Cells by Ginsenoside Rb1 via Inhibiting NF-κB, JNK and p38 Signaling Pathways

Cited by 127 publications

References 44 publications

Endothelial pannexin 1 channels control inflammation by regulating intracellular calcium

Endothelial pannexin 1 channels control inflammation by regulating intracellular calcium

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

Effects of different polyaniline emeraldine compositions in electrodepositing ginsenoside encapsulated poly(lactic‐co‐glycolic acid) microcapsules coating: Physicochemical characterization and in vitro evaluation

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