Ginsenoside Rh1 protects human endothelial cells against lipopolysaccharide-induced inflammatory injury through inhibiting TLR2/4-mediated STAT3, NF-κB, and ER stress signaling pathways

Jin, Yujin; Nguyen, Thuy Le Lam; Myung, Chang‐Seon; Heo, Kyung‐Sun

doi:10.1016/j.lfs.2022.120973

Cited by 18 publications

(10 citation statements)

References 50 publications

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“…Notably, LPS specifically mediates TLR4-activation and initiates downstream pathways, thereby releasing a series of inflammatory factors. In addition, LPS may activate TLR2 receptors and induce higher protein levels, causing an inflammatory response and oxidative stress. − Our previous study confirmed the presence of TLR2 and TLR4 as important receptors for PSPP-1. The results of the present study indicate that LPS treatment markedly increases both TLR2 and TLR4 expressions, whereas PSPP-1 treatment reduces their expressions.…”

Section: Discussionsupporting

confidence: 58%

Purple Sweet Potato Polysaccharide Exerting an Anti-inflammatory Effect via a TLR-Mediated Pathway by Regulating Polarization and Inhibiting the Inflammasome Activation

Song,

Niu,

Zhang

et al. 2024

J. Agric. Food Chem.

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Purple sweet potato polysaccharide (PSPP-1) is a novel glucan; this study aimed to examine the anti-inflammatory effect of PSPP-1 and elucidate its potential mechanisms. Lipopolysaccharide (LPS)-induced RAW264.7 was used as the model of inflammation, cell viability, and levels of nitric oxide (NO), reactive oxygen species (ROS), and calcium ion (Ca 2+ ) were analyzed. ELISA and qPCR were used to assess the productions and mRNA expression of cytokines, and Western blotting was used to assess protein expressions in the TLR-mediated pathway, macrophage polarization, and inflammasome activation. The results demonstrated PSPP-1 inhibited cell proliferation and markedly decreased NO, ROS, and Ca 2+ levels. Moreover, PSPP-1 suppressed the secretions and mRNA expressions of pro-inflammatory cytokines and increased those of anti-inflammatory cytokines. Furthermore, PSPP-1 could exert anti-inflammatory effects through different pathways mediated by both TLR2 and TLR4, which modulated the expressions of essential proteins in the myeloid differentiation factor 88 (MyD88)-dependent and toll/IL-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-dependent signaling pathways. PSPP-1 even regulated the polarization of M1/M2 macrophages and inhibited the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation. These findings indicate that PSPP-1 can suppress LPS-induced inflammation via multiple pathways and may be a potential agent for therapeutic inflammation-related pathophysiological processes and disorders.

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Section: Discussionsupporting

confidence: 58%

Purple Sweet Potato Polysaccharide Exerting an Anti-inflammatory Effect via a TLR-Mediated Pathway by Regulating Polarization and Inhibiting the Inflammasome Activation

Song,

Niu,

Zhang

et al. 2024

J. Agric. Food Chem.

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“…Nevertheless, Yang et al ( 31 ) reported that TSG-6 from bone marrow mesenchymal stem cells can protect against intervertebral disc degeneration via the TLR2/NF-κB signaling pathway. Moreover, TLR2 takes part in the inflammation response by activating the STAT3 and MAPK pathways ( 32 , 33 ). Additionally, Wu et al ( 34 ) showed that resveratrol blocks the IL-6/JAK/STAT3 pathway to protect HNPCs from degeneration.…”

Section: Discussionmentioning

confidence: 99%

S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells

Tian,

Gao,

Xia

et al. 2024

Exp Ther Med

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Sphingosine 1-phosphate receptor 3 (S1PR3) participates in the inflammatory response in multiple types of diseases. However, the biological role of S1PR3 in intervertebral disc degeneration and the underlying mechanism are unclear. The aim of the present study was to investigate the functional role and the mechanism of S1PR3 in lipopolysaccharide (LPS)-induced human nucleus pulposus cells. The expression of S1PR3 and Toll-like receptor (TLR) 2 in LPS-induced nucleus pulposus (NP) cells was investigated using western blotting. The Cell Counting Kit-8 assay was used to detect cell proliferation, and the levels of inflammatory factors were detected using ELISA. Flow cytometry and western blotting were used for the assessment of apoptosis. The deposition of extracellular matrix (ECM) proteins was investigated using reverse transcription-quantitative PCR and western blotting. In addition, western blotting was used to investigate the protein expression levels of phosphorylated (p)-STAT3, STAT3, p-JNK, JNK, p-ERK, ERK, p-p38 and p38associated with STAT3 and MAPK signaling. S1PR3 expression was reduced, while TLR2 expression was elevated in LPS-induced human nucleus pulposus cells (HNPC). S1PR3 overexpression increased HNPC viability, inhibited the inflammatory response and suppressed apoptosis. Meanwhile, S1PR3 overexpression regulated the expression of ECM-related proteins. Additionally, overexpression of S1PR3 inhibited the expression of the TLR2-regulated STAT3 and MAPK pathways in LPS-induced HNPCs. Furthermore, TLR2 overexpression partially offset the impacts of S1PR3 overexpression on HNPC viability, apoptosis level, inflammation and as ECM degradation. In conclusion, STAT3 overexpression suppressed viability injury, the inflammatory response and the level of apoptosis and alleviated ECM protein deposition in HNPCs through the TLR2/STAT3 and TLR2/MAPK pathways, which may offer a promising candidate for the amelioration of intervertebral disc degeneration.

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“…The inhibitory effects on the NF-κB activation of ginsenosides are acquired by targeting different steps of the NF-κB signaling pathway. For instance, Rh1 targets the initial step of the canonical NF-κB signaling pathway by suppressing the expression of TLR2 and TLR4, ameliorating the inflammatory process in HUVEC cells [ 92 ]. Rg3 upregulates the non-canonical NF-κB pathway by inducing RelB activation, which induces the epigenetic silencing of p65 target genes [ 96 ].…”

Section: Discussionmentioning

confidence: 99%

“…Metformin is a drug for type 2 diabetes that also has significant anti-inflammatory effects on monocytes [ 182 ]. Surprisingly, it was confirmed that Rh1 has the effect of inhibiting the expression of TNF-α and IL-1β, comparable to metformin [ 92 ]. The administration of 100 μg/kg of Rb1 also exerted stronger inhibitory effects on the expression of pro-inflammatory cytokines compared to 5 mg/kg of diclofenac, which is one of the well known NSAIDs for stroke and arthritis [ 148 ].…”

Section: Discussionmentioning

confidence: 99%

“…Jin et al used human umbilical vascular endothelial cells (HUVECs) to examine the therapeutic potential of ginsenoside Rh1 on LPS-induced inflammation [ 92 ]. LPS treatment dramatically increased the activation of the NF-κB signaling pathway followed by the activation of adhesion molecules, such as vascular cell adhesion protein-1 and intracellular adhesion molecule-1; however, Rh1 treatment reversed the LPS-mediated effects by blocking TLR2 and TLR4 activation.…”

Section: Pharmacological Activities Of Ginsenosides On Inflammatory D...mentioning

confidence: 99%

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Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

Jang

Hwang

Cho

2023

IJMS

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Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.

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Ginsenoside Rh1 protects human endothelial cells against lipopolysaccharide-induced inflammatory injury through inhibiting TLR2/4-mediated STAT3, NF-κB, and ER stress signaling pathways

Cited by 18 publications

References 50 publications

Purple Sweet Potato Polysaccharide Exerting an Anti-inflammatory Effect via a TLR-Mediated Pathway by Regulating Polarization and Inhibiting the Inflammasome Activation

Purple Sweet Potato Polysaccharide Exerting an Anti-inflammatory Effect via a TLR-Mediated Pathway by Regulating Polarization and Inhibiting the Inflammasome Activation

S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

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