Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD

Peng, Zhenyu; Zhang, Wenxuan; Qiao, Jianfeng; He, Ben

doi:10.1016/j.intimp.2018.06.033

Cited by 90 publications

(64 citation statements)

References 38 publications

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“…Some mitochondrial actions of melatonin were shown to be absent in Sirt1 –/– mice . In a rat COPD model, beneficial effects of melatonin, which included reduced NLRP3 inflammasome formation and IL‐1β levels, were inhibited by EX527 . Despite of the diversity of models in which a suppression of melatonin's actions by SIRT1 inhibition was observed, the outcome of these studies was remarkably consistent.…”

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 88%

“…Importantly, many effects of SIRT1 that are relevant to the suppression or avoidance of inflammation have been also observed upon treatment with melatonin (Figure ). In addition to the inhibition of NF‐κB activation, to Nrf2 upregulation, and to the avoidance of NLRP3 inflammasome activation, several further anti‐inflammatory actions of SIRT1 have become known. This concerns, for example, an inhibition of TLR4, which was demonstrated in renal collecting duct cells by either SIRT1 overexpression or activation by SRT1720, effects that were blocked by Sirt1 siRNA or the sirtuin inhibitors sirtinol and EX527 .…”

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 99%

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Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

347

350

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 88%

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

347

350

View full text Add to dashboard Cite

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“…Interestingly, the activation of NF‐κB is important for upregulating the expression of NLRP3 . The NLRP3 inflammasome, a complex composed of NLRP3, ASC, and caspase‐1, is one of the best investigated inflammasomes and has been demonstrated to promote the production of proinflammatory cytokines . Upon stimulated by several substances, including LPS, the specific activation of NLRP3 and the assembly of the inflammasome complex can be achieved to recruit and activate caspase‐1 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the activation of NF‐κB is important for upregulating the expression of the NLR family and the pyrin domain containing 3 (NLRP3) inflammasome . The NLRP3 inflammasome, a complex composed of NLRP3, ASC, and caspase‐1, is one of the best investigated inflammasomes and has been demonstrated to promote the production of proinflammatory cytokines and apoptosis …”

Section: Introductionmentioning

confidence: 99%

“…14 The NLRP3 inflammasome, a complex composed of NLRP3, ASC, and caspase-1, is one of the best investigated inflammasomes and has been demonstrated to promote the production of proinflammatory cytokines and apoptosis. 10,15 Ginseng is one of the most frequently used traditional Chinese medicines in the world, and ginsenosides are the main bioactive components of ginseng. Rg1 has been previously investigated for its anti-inflammatory and antiapoptotic properties.…”

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confidence: 99%

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

Luo

Yan

Sun

et al. 2019

J of Cellular Biochemistry

140

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Sepsis‐induced myocardial dysfunction (SIMD) causes high mortality in seriously ill patients. Ginsenoside Rg1 has been proven to have effective anti‐inflammatory and antiapoptotic properties. However, the specific role of Rg1 in SIMD and the molecular mechanism remain unclear. Hence, we aimed to investigate the latent effects of ginsenoside Rg1 against SIMD and explore its underlying mechanisms. Male C57BL/6J mice and neonatal rat cardiomyocytes (NRCMs) were used as in vivo and in vitro models, respectively. Western blot analysis was used to detect the level of protein expression, and reverse transcription polymerase chain reaction was conducted to determine the messenger RNA expression of inflammatory factors. The terminal deoxynucleotidyl transferase‐mediated nick end labeling assay and flow cytometry were used to determine the apoptosis rate. Echocardiography was performed to assess cardiac function. The results showed that Rg1 improved cardiac function and attenuated lipopolysaccharide (LPS)‐induced apoptosis and inflammation in mice. In addition, in NRCMs, Rg1 downregulated the expression of LPS‐induced inflammatory cytokines and reversed the increased expression of Toll‐like receptor 4 (TLR4), nuclear factor‐κB (NF‐κB), and NOD‐like receptor 3 (NLRP3). In addition, treatment with TLR4 small interfering RNA (siRNA), a p‐NF‐κB inhibitor, or NLRP3 siRNA suppressed LPS‐induced apoptosis and inflammation. In conclusion, Rg1 can attenuate LPS‐induced inflammation and apoptosis both in NRCMs and septic mice and restore impaired cardiac function. Moreover, Rg1 may exert its effect via blocking the TLR4/NF‐κB/NLRP3 pathway.

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Anemonin inhibits sepsis‐induced acute kidney injury via mitigating inflammation and oxidative stress

Liu,

Li,

2023

Biotech and App Biochem

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Elevated inflammation and oxidative stress (OS) are the main pathologic features of acute kidney injury (AKI)‐caused by sepsis. Here, we made an investigation into the protective effects of the natural compound Anemonin (ANE) on sepsis‐induced AKI both in vitro and in vivo. Lipopolysaccharide (LPS) was applied to construct an in vitro AKI model in renal tubular epithelial cells, and the septic C57BL/6J mouse model was constructed via cecal ligation and puncture (CLP). Cell viability and apoptosis were detected. The levels of p53, Bax, Bcl2, Caspase3, Caspase8, Caspase9, AMP‐activated protein kinase (AMPK), Sirt‐1, and forkhead box O3 were determined by Western Blot or RT‐PCR. The reactive oxygen species level and OS markers were measured. Furthermore, the pathological changes of kidneys were evaluated by hematoxylin–eosin staining and immunohistochemistry. As per the information presented, ANE improved LPS‐elicited apoptosis, inflammatory response, and OS in a dose‐dependent pattern in renal tubular epithelial cells. Besides, ANE activated the AMPK/Sirt‐1 pathway, and the AMPK inhibitor (Compound C) and Sirt‐1 inhibitor (EX‐527) significantly attenuated ANE‐mediated protection on renal tubular epithelial cells. In vivo, ANE mitigated the levels of serum creatinine and urea nitrogen in the CLP‐induced mouse sepsis model, reduced the renal tissue injury score, and attenuated OS, inflammation, and apoptosis levels in the kidney. Taken together, this study suggested that ANE has protective effects in sepsis‐triggered AKI through repressing inflammation, OS, and cell apoptosis by activating the AMPK/Sirt‐1 pathway.

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Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD

Cited by 90 publications

References 38 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

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

Anemonin inhibits sepsis‐induced acute kidney injury via mitigating inflammation and oxidative stress

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