α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice

Ge, Yun; Xu, Xin; Liang, Qiqiang; Xu, Yongshan; Huang, Man

doi:10.1007/s00011-019-01232-0

Cited by 28 publications

(17 citation statements)

References 41 publications

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“…Additionally, Xiao et al [12] demonstrated that NLRP3 activation mediated by oxidative stress plays an important role in susceptibility to AKI in diabetes models. Studies have also shown that the NLRP3 inflammasome contributes to sepsis [32,33]. Based on these findings, it can be hypothesised that the NLRP3 inflammasome is a potential target for AKI treatment.…”

Section: Discussionmentioning

confidence: 94%

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Gao

Dai

et al. 2020

J Transl Med

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Background: We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsisinduced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. Methods: Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. Key results: PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin−/− mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkindependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. Conclusions: These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.

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Section: Discussionmentioning

confidence: 94%

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Gao

Dai

et al. 2020

J Transl Med

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“…Exogenous H 2 S can inhibit the expression of NLRP3 inflammasome induced by fatty acid and attenuate the cardiomyocytes injury induced by high glucose through inhibiting the activation of NLRP3 inflammasome (Luo et al, 2017; Huang et al, 2016). In addition, exogenous H 2 S can play a protective role by inhibiting autophagy, while enhanced autophagy can inhibit NLRP3 inflammasome (Yang et al, 2018; Ge et al, 2019). So far, the relationship among H 2 S, autophagy and NLRP3 inflammasome has not been studied by others.…”

Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via AMPK-mTOR pathway

2019

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The aim of this study was to investigate whether exogenous hydrogen sulfide (H 2 S) could mitigate NLRP3 inflammasome-mediated inflammation through promoting autophagy via the AMPK-mTOR pathway in L02 cells. L02 cells were stimulated with different concentrations of oleic acid (OA), then cell viability and the protein expression of NLRP3 and pro-caspase-1 were detected by MTT and western blot, respectively, to determine appropriate OA concentration in this study. The cells were divided into four groups: the cells in the control group were cultured with RPMI-1640 for 24.5 h; the cells in the OA group were cultured with RPMI-1640 for 0.5 h, then were stimulated with 1.2 mmol/l OA for 24 h; the cells in the NaHS+OA group were pretreated with sodium hydrogen sulfide (NaHS, a donor of H 2 S) for 0.5 h before exposure to OA for 24 h; and the cells in the NaHS group were treated with NaHS 0.5 h, then were cultured with RPMI-1640 for 24 h. Subsequently, the cells in every group were collected and the protein expression of NLRP3, procaspase-1, cleaved caspase-1, P62, LC3, Beclin1, T-AMPK, P-AMPK, T-mTOR, P-mTOR and the level of IL-1β were detected by western blot and ElISA, respectively. Exogenous H 2 S reduced the level of NLRP3, caspase-1, P62, IL-1β and the ratio of P-mTOR/T-mTOR induced by OA and increased the ratio of LC3 II/I and the protein expression of Beclin1 suppressed by OA. This study demonstrates for the first time that H 2 S might suppress NLRP3 inflammasome-mediated inflammation induced by OA through promoting autophagy via the AMPK-mTOR pathway. It provides a theoretical basis for the further study of the anti-inflammatory mechanism of H 2 S.

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“…Macrophages are important regulatory cells in the sepsis-related inflammatory response because they produce proinflammatory factors and mediators [ 29 ]. Macrophages are able to release large numbers of inflammatory factors, such as IL-1β, TNF-α, and IL-6, after CLP or LPS treatment [ 30 , 31 ]. In addition, overactivated inflammation causes acute systemic organ injuries during the early stage of organ failure.…”

Section: Discussionmentioning

confidence: 99%

Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling

Zhang

et al. 2020

Acta Pharmacol Sin

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Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3–10 μM) dose-dependently inhibited the expression levels of IL-6, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-β-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.

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α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice

Cited by 28 publications

References 41 publications

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury

Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via AMPK-mTOR pathway

Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling

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