Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Huang, Chung‐Cheng; Wang, Shu-Chi; Chen, I-Chen; Chen, Yi-Ting; Liu, Po-Len; Fang, Shih-Hua; Huang, Shu‐Pin; Yeh, Hsin Chih; Liu, Ching-Chih; Lee, Po-Yen; Lin, Tzu-Chieh; Cheng, Wei‐Chung; Su, Chin-Chuan; Wu, Hsin‐Lung; Chen, Yuan-Ru; Li, Chia-Yang

doi:10.3390/ph14060588

Cited by 24 publications

(14 citation statements)

References 39 publications

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“…After macrophages were treated with proinflammatory stimuli, NO and PGE2 were generated from iNOS and COX-2, respectively. In addition, cPLA2 phosphorylation was involved in COX-2-dependent PGE2 generation in macrophages [19,34]. This result is the first to demonstrate that 1-NP-induced NO generation occurs through iNOS upregulation and PGE2 production by the upregulation of COX-2 through cPLA2 phosphorylation.…”

Section: Discussionmentioning

confidence: 77%

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Tsai

Chen

Liu

et al. 2021

Toxics

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Air pollution is a major environmental and public health problem worldwide. A nitro-polycyclic aromatic hydrocarbon and the most abundant air pollutant in diesel engine exhaust, 1-nitropyrene (1-NP), is caused by the incomplete combustion of carbonaceous organic substances. Macrophages are effector cells of the innate immune cells that provide resistance in the peripheral tissue. The overactivation of macrophages results in inflammation. The generation of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor alpha, is induced by 1-NP in a concentration-dependent manner in macrophages. In this study, the production of proinflammatory mediators, such as nitrogen oxide and prostaglandin E2, was induced by 1-NP in a concentration-dependent manner through the expression of iNOS and COX2. The generation of proinflammatory cytokines, iNOS, and COX2 was induced by 1-NP through nuclear factor (NF)-κB p65 phosphorylation and the degradation of its upstream factor, IκB. Finally, Akt phosphorylation was induced by 1-NP in a concentration-dependent manner. These findings suggest that 1-NP exhibits a proinflammatory response through the NF-κB pathway activation due to Akt phosphorylation.

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Section: Discussionmentioning

confidence: 77%

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Tsai

Chen

Liu

et al. 2021

Toxics

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“…Both MAPK and NF-κB signaling pathways are known to drive inflammation-associated gene expressions during LPS-induced inflammation. 24 , 25 To assess whether punicalagin regulated the activation of MAPK and NF-κB signaling pathways by LPS-induced BV2 cells, cells were pre-treated with various doses of punicalagin (0 to 100 μM) for 30 min following 1 μg/mL LPS treatment for 6 h. The expression of phospho-ERK, ERK, phospho-JNK, JNK, phospho-p38, and p38 was examined by Western blot. As shown in Figure 3A–D , punicalagin significantly decreased the phosphorylation of ERK, JNK, and p38 in LPS-induced BV2 cells in a dose-dependent manner.…”

Section: Resultsmentioning

confidence: 99%

“… 23 In addition, the MAPK cascade and NK-κB signaling pathway both regulate the expression and production of LPS-induced proinflammatory cytokines. 24 NF-κB has been demonstrated to play an integral role in the progression of Alzheimer’s disease 44 and ischemic stroke. 45 A previous murine model in vivo and in vitro study revealed the anti-neuroinflammatory effect of punicalagin on microglia and astrocytes by inhibiting the production of proinflammatory cytokines including IL-1β, IL-6 and TNF-α and interfering with NF-κB signaling via binding to its subunit p50 directly.…”

Section: Discussionmentioning

confidence: 99%

Punicalagin Attenuates LPS-Induced Inflammation and ROS Production in Microglia by Inhibiting the MAPK/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Lo¹,

Liu²,

Li³

et al. 2022

JIR

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Purpose Neurodegenerative diseases are associated with neuroinflammation along with activation of microglia and oxidative stress, but currently lack effective treatments. Punicalagin is a natural bio-sourced product that exhibits anti-inflammatory effects on several chronic diseases; however, the anti-inflammatory and anti-oxidative effects on microglia have not been well examined. This study aimed to investigate the effects of punicalagin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and the production of ROS using murine microglia BV2 cells. Methods BV2 cells were pre-treated with punicalagin following LPS treatment to induce inflammation. The secretion of NO and PGE 2 was analyzed by Griess reagent and ELISA respectively, while the expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were analyzed using Western blotting, the production of IL-6 was measured by ELISA, and the activity of NF-κB was detected using promoter reporter assay. To examine whether punicalagin affects NLRP3 inflammasome activation, BV2 cells were stimulated with LPS and then treated with ATP or nigericin. The secretion of IL-1β was measured by ELISA. The expressions of NLRP3 inflammasome-related proteins and phospho IκBα/IκBα were analyzed using Western blotting. The production of intracellular and mitochondrial ROS was analyzed by flow cytometry. Results Our results showed that punicalagin attenuated inflammation with reduction of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1β, and reduction of IL-6 led to inhibition of STAT3 phosphorylation by LPS-induced BV2 cells. Punicalagin also suppressed the ERK, JNK, and p38 phosphorylation, attenuated NF-κB activity, inhibited the activation of the NLRP3 inflammasome, and reduced the production of intracellular and mitochondrial ROS by LPS-induced BV2 cells. Conclusion Our results demonstrated that punicalagin attenuated LPS-induced inflammation through suppressing the expression of iNOS and COX-2, inhibited the activation of MAPK/NF-κB signaling pathway and NLRP3 inflammasome, and reduced the production of ROS in microglia, suggesting that punicalagin might have the potential in treating neurodegenerative diseases.

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“…To improve the prognosis of HBV-HCC patients, we screened 13 small molecule compounds using the CMap database. Piperlongumine can reduce colitis-associated colorectal cancer ( 40 ) and relieve sepsis by attenuating the activation of inflammasomes ( 41 ). From the enrichment results, piperlongumine acts on the HIF-1 signaling pathway and lyase activity, while fisetin regulates NF-kB transcription factor activity.…”

Section: Discussionmentioning

confidence: 99%

Genomic analysis quantifies pyroptosis in the immune microenvironment of HBV-related hepatocellular carcinoma

Zhang

et al. 2022

Front. Immunol.

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Pyroptosis, a way of pro-inflammatory death, plays a significant part in the tumor microenvironment (TME). A recent study has shown that the hepatitis C virus changes the TME by inducing pyroptosis against hepatocellular carcinoma (HCC). However, compared to TME in hepatitis C virus-infected HCC, the exploration of immune characteristics and response to immunotherapy associated with the pyroptosis phenotype is still insufficient in hepatitis B virus-related HCC (HBV-HCC). Our study constructed pyroptosis-score (PYS) via principal-component analysis (PCA) to unveil the link between pyroptosis and tumor immunity in 369 HBV-HCC patients. Compared with the low-PYS group, subjects with higher PYS were associated with poor prognosis but were more susceptible to anti-PD-L1 treatment. In addition, we found that PYS can serve independently as a prognostic factor for HBV-HCC, making it possible for us to identify specific small molecule drugs with a potential value in inhibiting tumors via targeting pyroptosis. Also, the target genes predicted by the Weighted gene co-expression network analysis (WGCNA) and pharmacophore model were enriched in the HIF-1 signaling pathway and NF-kB transcription factor activity, which were related to the mechanism of inflammation-driven cancer. The PYS is extremely important in predicting prognosis and responses to immunotherapy. New treatment strategies for inflammation-driven cancers may be found by targeting pyroptosis.

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Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Cited by 24 publications

References 39 publications

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Punicalagin Attenuates LPS-Induced Inflammation and ROS Production in Microglia by Inhibiting the MAPK/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Genomic analysis quantifies pyroptosis in the immune microenvironment of HBV-related hepatocellular carcinoma

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