Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF‐kB/NLRP3 pathway

Luo, Man; Yan, Dongsheng; Sun, Qiang; Tao, Jiali; Xu, Liang; Sun, Hong; Zhao, Hongmei

doi:10.1002/jcb.29556

Cited by 140 publications

(87 citation statements)

References 39 publications

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“…Tlr4 can activate myeloid differentiation factor 88 (Myd88)-dependent pathways (6). Tlr4 can also regulate the transcriptional activity of nF-κB and interferon regulating factor 3 (IRF3), which promotes the production of inflammatory factors (7)(8)(9). as a member of Tlr family, Tlr2 can participate in the inflammatory response by modulating the Myd88 signaling pathway, and the activation of nF-κB and mitogen activated protein kinase (MaPK) (10).…”

Section: Introductionmentioning

confidence: 99%

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways

Huang

Yang

et al. 2020

Mol Med Rep

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The revascularization of blood vessels after myocardial infarction can lead to serious myocardial damage. Previous studies showed that radioprotective 105 kda protein (RP105) is a specific negative regulator of myocardial ischemia reperfusion injury (Miri). rP105 can modulate the Toll-like receptor (Tlr)2/Tlr4 signaling pathways. However, the synergistic effect of Tlr2/4 regulated by rP105 during Miri requires further investigation. To determine this effect, a Miri model was established in rats in the present study. The expression of rP105 was depleted by transfecting rP105-sirna and then detected using western blotting. Furthermore, the myocardium tissue was stained with the hematoxylin and eosin staining. Knockdown of rP105 promoted the activity of serum myocardial enzymes during Miri and increased myocardial infarction. The present results indicated that knockdown of rP105 activated the Tlr2/4 signaling pathway by modulating the myeloid differentiation primary response 88 and nF-κB signaling pathways. Furthermore, decreased expression of rP105 promoted myocardial cell apoptosis, which induced the damage of myocardial ischemic reperfusion. The present results suggested both Tlr2 and Tlr4 as key targets of rP105, thus rP105 may be a promising candidate to facilitate the development of novel therapeutic strategies for Miri.

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Section: Introductionmentioning

confidence: 99%

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways

Huang

Yang

et al. 2020

Mol Med Rep

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“…The present study found that IL-32 also promoted TLR4, NOD1 and NOD2 expression in a concentration-dependent manner. Notably, NOD1/2 and TLR4 are known to activate NF-κB signaling, which is able to trigger NLRP3 activation (36)(37). Therefore, the present results indicated that IL-32 could also induce inflammation and NLRP3-mediated pyroptosis by activating pattern recognition receptors.…”

Section: Discussionmentioning

confidence: 54%

IL-32 exacerbates adenoid hypertrophy via activating NLRP3-mediated cell pyroptosis, which promotes inflammation

et al. 2021

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Adenoid hypertrophy (AH) is a common pediatric disease caused by inflammatory stimulation. The pro-inflammatory cytokine IL-32 has been reported to promote airway inflammation and also be involved in the pyroptosis pathway. However, whether IL-32 can contribute to AH by mediating pyroptosis remains to be elucidated. The present study aimed to investigate the role of IL-32 in AH and determine the potential underlying mechanisms. Adenoid tissues were collected from healthy children and children with AH, and the expression of IL-32, NACHT LRR and PYD domains-containing protein 3 (NLRP3) and IL-1β in normal and hypertrophic tissues were measured. Human nasal epithelial cells (HNEpCs) were exposed to a series of IL-32 concentrations. HNEpCs with or without IL-32 silencing were stimulated with lipopolysaccharide (LPS), and cell proliferation, cell apoptosis, gasdermin D (GSDMD) activation, production of inflammatory cytokines and the expression levels of proteins related to the potential mechanisms were evaluated by Cell Counting Kit-8, flow cytometry, immunofluorescence staining, ELISA and western blot assays, respectively. The results showed that IL-32, NLRP3 and IL-1β exhibited higher expression in adenoid tissues with AH compared with normal tissues. In HNEpC cells, treatment with IL-32 (2 and 10 ng/ml) promoted cell proliferation, while 50 ng/ml IL-32 inhibited cell proliferation at 12, 24 and 48 h post-treatment. IL-32 (2, 10 and 50 ng/ml) also resulted in differing degrees of apoptosis, GSDMD activation, release of IL-1β, IL-6 and TNF-α, and increased protein expression levels of NLRP3, cleaved-caspase-1, activated GSDMD, nucleotide-binding oligomerization domain-containing protein (NOD) 1/2 and Toll-like receptor (TLR)4 in a concentration-dependent manner. In addition, compared with the LPS group, IL-32 knockdown significantly inhibited LPS-induced enhancement of cell proliferation, cell apoptosis, GSDMD activation and production of inflammatory cytokines, and reversed the increased protein expression of NLRP3, cleaved-caspase-1, activated GSDMD, NOD1/2 and TLR4. In conclusion, IL-32 may play a role in the progression of AH via promoting inflammation, and the potential mechanism may involve the activation of NLRP3-mediated pyroptosis.

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“…It has been reported that the inhibition of NLRP3 inflammasome activity could significantly decrease tissue inflammatory damage and inhibit apoptosis in LPS-induced acute kidney injury (53). A recent study reported that Rg1 could attenuate LPS-induced inflammation and apoptosis both in neonatal rat cardiomyocytes and septic mice and restore impaired cardiac function by blocking the TLR4/NF-κB/NLRP3 pathway (54). It has been reported that excessive ROS generation can activate the NLRP1 inflammasome and induce macrophage apoptosis in vitro and in vivo; although these effects can be significantly inhibited by pretreatment with ROS inhibitors (55).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 alleviates lipopolysaccharide‑induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells

et al. 2021

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Lipopolysaccharide (LPS) is a toxic component of cell walls of Gram-negative bacteria that are widely present in gastrointestinal tracts. Increasing evidence showed that LPS plays important roles in the pathogeneses of neurodegenerative disorders, such as Alzheimer's disease (AD). NADPH oxidase s2 (NOX2) is a complex membrane protein that contributes to the production of reactive oxygen species (ROS) in several neurological diseases. The NLRP1 inflammasome can be activated in response to an accumulation of ROS in neurons. However, it is still unknown whether LPS exposure can deteriorate neuronal damage by activating NOX2-NLRP1 inflammasomes. Ginsenoside Rg1 (Rg1) has protective effects on neurons, although whether Rg1 alleviates LPS-induced neuronal damage by inhibiting NOX2-NLRP1 inflammasomes remains unclear. In the present study, the effect of concentration gradients and different times of LPS exposure on neuronal damage was investigated in HT22 cells, and further observed the effect of Rg1 treatment on NOX2-NLPR1 inflammasome activation, ROS production and neuronal damage in LPS-treated HT22 cells. The results demonstrated that LPS exposure significantly induced NOX2-NLRP1 inflammasome activation, excessive production of ROS, and neuronal damage in HT22 cells. It was also shown that Rg1 treatment significantly decreased NOX2-NLRP1 inflammasome activation and ROS production and alleviated neuronal damage in LPS-induced HT22 cells. The present data suggested that Rg1 has protective effects on LPS-induced neuronal damage by inhibiting NOX2-NLRP1 inflammasomes in HT22 cells, and Rg1 may be a potential therapeutic approach for delaying neuronal damage in AD.

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Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF‐kB/NLRP3 pathway

Cited by 140 publications

References 39 publications

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways

IL-32 exacerbates adenoid hypertrophy via activating NLRP3-mediated cell pyroptosis, which promotes inflammation

Ginsenoside Rg1 alleviates lipopolysaccharide‑induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells

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