Ginsenoside Rg1 attenuates protein aggregation and inflammatory response following cerebral ischemia and reperfusion injury

Zheng, Tianyang; Jiang, Hong; Jin, Rihua; Zhao, Yiming; Bai, Yang; Xu, Haidong; Chen, Yong

doi:10.1016/j.ejphar.2019.02.018

Cited by 47 publications

(31 citation statements)

References 47 publications

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“…Moreover, several reports indicate that NF‐κB depression is also involved in TJs protection (Zhang, Su, et al, ). Previous investigations show that PNS or the active compounds can attenuate inflammatory injury via the suppression of the NF‐κB activation (Fan et al, ; Zheng et al, ). In our study, the DNA‐binding activity of NF‐κB that translocated into the nucleus was significantly enhanced with LPS stimulation, which was opposite to Nrf2 binding activity.…”

Section: Discussionmentioning

confidence: 99%

“…As we know, PNS is a mixture, of which notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, ginsenoside Rb 1 , and ginsenoside Rd are the main active components. Previous investigations have shown that all the five components exhibit efficient antioxidant and anti‐inflammatory activity, and the mechanisms are related to the activation of Nrf2 and inhibition of NF‐κB (González‐Burgos, Fernández‐Moriano, Lozano, Iglesias, & Gómez‐Serranillos, ; Kim et al, ; Lee et al, ; Meng et al, ; Saw et al, ; Sun, Xiao, Sun, & Wu, ; Wang et al, ; Zheng et al, ). Therefore, which main component plays a major role in the protective effects, and whether different active constituents combinations exist synergistic effects should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…We recently demonstrated that PNS could protect cerebral microvascular endothelial cells against oxygen‐glucose deprivation/reperfusion (OGD/R) induced oxidative stress injury of BBB barrier function, relating to the activation of Akt/Nrf2 antioxidant pathway (Hu et al, ). Meanwhile, it is reported that PNS or the active compounds could inhibit the inflammatory responses and adhesion events by suppression of the NF‐κB activation (Dou et al, ; Lee, Hyam, Jang, Han, & Kim, ; Zheng et al, ). Additionally, PNS alleviate the monocyte adhesion and protect the arteries in an atherogenic model involving with the Nrf2 activation (Fan, Liu, He, Li, & He, ).…”

Section: Introductionmentioning

confidence: 99%

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Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Liu

et al. 2019

Phytotherapy Research

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Dysfunction of the blood‐brain barrier (BBB) is a prerequisite for the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are well‐known factors accounting for BBB injury. Panax notoginseng saponins (PNS), a clinical commonly used drug against cerebrovascular disease, possess efficient antioxidant and anti‐inflammatory activity. In the present study, the protective effects of PNS on lipopolysaccharide (LPS)‐insulted cerebral microvascular endothelial cells (bEnd.3) were assessed and the underlying mechanisms were investigated. The results showed that PNS mitigated the decrease of Trans‐Endothelial Electrical Resistance, increase of paracellular permeability, and loss of tight junction proteins in bEnd.3 BBB model. Meanwhile, PNS suppressed the THP‐1 monocytes adhesion on bEnd.3 monolayer. Moreover, PNS prevented the pro‐inflammatory cytokines secretion and reactive oxygen species generation in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that PNS promoted the Akt phosphorylation, activated Nrf2 antioxidant signaling, and inhibited the NF‐κB activation. All the effects of PNS could be abolished by PI3K inhibition at different levels. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant defense system depending on PI3K/Akt and inhibits NF‐κB inflammatory signaling to attenuate LPS‐induced BBB disruption and monocytes adhesion on cerebral endothelial cells in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Liu

et al. 2019

Phytotherapy Research

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“…Growing evidence suggests that Rg1 exerts signi cant antioxidant, anti-in ammatory and protective effects in neurological disease models in vivo and in vitro studies [62,63]. Our previous study demonstrated that Rg1 treatment could reduce oxidative stress and neuroin ammation and delay neuronal senescence in hippocampal neurons in vitro [17].…”

Section: Discussionmentioning

confidence: 97%

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

Zhang¹,

Su²,

Sun³

et al. 2020

Preprint

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Background: Oxidative stress and neuroinflammation play important roles in the whole pathogenesis of Alzheimer's disease (AD). NADPH oxidase 2 (NOX2) is an important enzyme that is responsible for ROS generation in many neurodegenerative diseases. The nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro-inflammatory molecules in neurons. However, it is still unclear whether inhibition of NOX2 and NLRP1 inflammasome decreases amyloid-beta (Aβ) generation and deposition in APP/PS1 mice. Ginsenoside Rg1 (Rg1) is an active component in ginseng, and maybe a potential agent for neurodegenerative diseases. In this study, we investigated the effects and mechanisms of Rg1 treatment on cognitive performance, neuronal damage, Aβ deposition and NOX2-NLRP1 inflammasome activation in APP/PS1 mice.Methods: WT and APP/PS1 mice were used in the experiment from 6 months (M) old to 9M old, and 6M APP/PS1 mice were used as pre-treatment controls. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral change and cognitive function. The H&E and Nissl staining were used to assess neuronal damage. We further examined PSD95 expression, Aβ generation and deposition, Tau and p-Tau expression, NOX2-mediated ROS generation and NLRP1 inflammasome activation by using immunofluorescence, western blot analysis, and real time q-PCR.Results: Rg1 treatment for 12 weeks alleviated learning and memory impairments and neuronal damage, decreased p-Tau level, APP expression and Aβ deposition in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the levels of ROS and IL-1β, and reduced the expressions of NOX2 and NLRP1 inflammasome in the brain cortex and hippocampus in APP/PS1 mice. Furthermore, apocynin (a NOX inhibitor) and NLRP1-siRNA treatment also alleviated cognitive impairments, neuronal damage and Aβ deposition, and reduced the expression of NLRP1 inflammasome in brain cortex and hippocampus in APP/PS1 mice.Conclusions: Rg1 treatment could alleviate learning and memory impairment, neuronal damage, and reduce Aβ generation and deposition by inhibiting NLRP1 inflammasome activation in APP/PS1 mice.

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“…Ginsenoside Rd confers neuroprotection and alleviates neurological deficits in ischemic stroke, and this neuroprotective effect is attributed to its capability of inhibiting microglial proteasome activity and sequential inflammation [38]. Ginsenoside Rg1 also attenuates ubiquitinated protein aggregation, suppresses inflammatory responses, and thus protects against cerebral ischemiareperfusion-induced injury [39].…”

Section: The Ubiquitin-proteasome Pathway Inhibition and Thementioning

confidence: 99%

The Role of Ubiquitin-Proteasome Pathway and Autophagy-Lysosome Pathway in Cerebral Ischemia

Chen

Qin

Tan

et al. 2020

Oxidative Medicine and Cellular Longevity

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The ubiquitin-proteasome pathway and autophagy-lysosome pathway are two major routes for clearance of aberrant cellular components to maintain protein homeostasis and normal cellular functions. Accumulating evidence shows that these two pathways are impaired during cerebral ischemia, which contributes to ischemic-induced neuronal necrosis and apoptosis. This review aims to critically discuss current knowledge and controversies on these two pathways in response to cerebral ischemic stress. We also discuss molecular mechanisms underlying the impairments of these protein degradation pathways and how such impairments lead to neuronal damage after cerebral ischemia. Further, we review the recent advance on the understanding of the involvement of these two pathways in the pathological process during many therapeutic approaches against cerebral ischemia. Despite recent advances, the exact role and molecular mechanisms of these two pathways following cerebral ischemia are complex and not completely understood, of which better understanding will provide avenues to develop novel therapeutic strategies for ischemic stroke.

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Ginsenoside Rg1 attenuates protein aggregation and inflammatory response following cerebral ischemia and reperfusion injury

Cited by 47 publications

References 47 publications

Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Ginsenoside Rg1 alleviates Aβ deposition and neuronal damage by inhibiting NLRP1 inflammasome activation in APP/PS1 mice

The Role of Ubiquitin-Proteasome Pathway and Autophagy-Lysosome Pathway in Cerebral Ischemia

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