Protective effects of wedelolactone on dextran sodium sulfate induced murine colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK signaling

2017 ◽  
Vol 94 ◽  
pp. 27-36 ◽  
Author(s):  
Wencheng Wei ◽  
Meiling Ding ◽  
Kai Zhou ◽  
Haifeng Xie ◽  
Mian Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Sodium Sulfate ◽  
Dextran Sodium Sulfate ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Ampk Signaling ◽  
Murine Colitis ◽  
Nlrp3 Inflammasome Activation

scholarly journals Vaspin Alleviates Osteoarthritis by Inhibiting NLRP3-mediated Inflammation

2021 ◽  
Author(s):  
Xianjie Zhu ◽  
Shiyou Dai ◽  
Baohua Xia ◽  
Jianbao Gong ◽  
Bingzheng Ma
Keyword(s):  
Nlrp3 Inflammasome ◽  
Wistar Rat ◽  
Cartilage Degradation ◽  
Pathological Process ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Collagen Formation ◽  
Nlrp3 Inflammasome Activation

Abstract Background:Osteoarthritis (OA) is a chronic degenerative joint bone disease characterized by cartilage degradation. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is associated with the inflammatory and metabolic responses to OA. However, the underlying mechanisms of the pathological process of OA are not clear. The aim of the present study was to examine the protective effects of vaspin both in vitro and in vivo.Methods:Monosodium iodoacetate (MIA)-induced Wistar rat model of OA was used to assess the in vivo effects of vaspin administered for 12 weeks. The characteristics of OA were evaluated by haematoxylin and eosin (H&E) and safranin O/fast green staining. The anti-inflammatory effect of vaspin was assessed using immunohistochemical, qRT-PCR, and western blotting analysis. Parallel experiments to detect the molecular mechanism through which vaspin prevents OA were performed using LPS-treated chondrocytes.Results:Our results showed that the degeneration of cartilage and upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-13 were ameliorated by vaspin. Additionally, vaspin suppressed the activation of TXNIP/NLRP3 and secretion of tumor necrosis factor ɑ and interleukin-1β in vivo. It was further confirmed that vaspin could also suppress LPS-induced NLRP3 inflammasome activation and reduce collagen formation in chondrocytes. Moreover, vaspin inhibited NLRP3 inflammasome activation by suppressing the ROS/TXNIP pathway.Conclusions: Vaspin inhibited OA by repressing TXNIP/NLRP3 activation in in vitro and in vivo models of OA, thus providing a novel therapeutic strategy for OA.

scholarly journals Neuroprotective effect of Estrogen Receptor α against neuroinflammation induced by hypoxia/ischemia via SIRT1-dependent AMPK pathway

2019 ◽  
Author(s):  
Z Z ◽  
He WQ ◽  
Cao XL ◽  
Tang B ◽  
Fan QY ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Nlrp3 Inflammasome ◽  
Neuroprotective Effect ◽  
Intraperitoneal Administration ◽  
Inflammasome Activation ◽  
In Vitro Production ◽  
Ampk Signaling ◽  
Ampk Pathway ◽  
Nlrp3 Inflammasome Activation

Abstract Background: Stroke-related damage in rats is protected against by estrogen which also has an anti-cerebral ischemia role mostly conducted via its association with estrogen receptor (ER) α .However,processes governing ER α-mediated neuroprotection are poorly comprehended. This study sought to establish whether ERα’s control of neuroinflammation caused by NLRP3 inflammasome activation emanating from SIRT1-AMPK signaling allowed ERα’s improvement of hypoxia/ischemic damage. Methods: The intraperitoneal administration of estrogen was performed to ovariectomized (bilaterally) (OVA) SD rats prior to middle cerebral artery occlusion (MCAO). The strong rise in NLRP3 inflammasome activation including caspase-1, ASC, IL-1β and IL-18 occurred following OVA and were specifically decreased following estrogen treatment. Moreover, the expression of Silent Information Regulator 1 (SIRT1) and ERα were reversed. The association between ERα-led inhibition of the NLRP3 inflammasome in conditions of hydrogen peroxide (H 2 O 2 ) and SIRT1-AMPK signaling were also examined. Results: Findings confirmed the prevention of NLRP3 inflammasome activation instigated by H 2 O 2 and the in vitro production of IL-1β, IL-18 together with the enhancement of this impact by SIRT1. Additionally, ERα's neuroprotective impact was prevented by inhibiting of AMPK. The synergistic impact of SIRT1 on ERα increased AMPK activation; however, SIRT1 knockout eliminated this. Conclusions: The findings indicate that inhibition of the NLRP3 inflammasome by ERα results in neuroprotection against hypoxia/ischemic injury and that ERα’s neuroprotection can be highly improved by the SIRT1-dependent AMPK pathway.

scholarly journals Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF-κB Pathway and NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qingfei Xiao ◽  
Zhihui Qu ◽  
Ying Zhao ◽  
Liming Yang ◽  
Pujun Gao
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Receptor Protein ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation ◽  
Underlying Mechanisms

Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators. Consistent with these results, the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced. Further study demonstrated that such inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-κB) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation, which may contribute to its anti-inflammatory effects. Together, these findings show that Ori may be an effective candidate for ameliorating LPS-induced inflammatory responses.

scholarly journals Inhibition of oxidative stress and NLRP3 inflammasome by Saikosaponin-d alleviates acute liver injury in carbon tetrachloride-induced hepatitis in mice

2020 ◽  
Vol 34 ◽  
pp. 205873842095059
Author(s):  
Yirong Chen ◽  
Renye Que ◽  
Liubing Lin ◽  
Yanting Shen ◽  
Jinkai Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Mice Model ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

NLRP3 inflammasome activation results in severe liver inflammation and injury. Saikosaponin-d (SSd) possesses anti-inflammatory and hepatoprotective effects. This study aimed to determine the protective effects of SSd on carbon tetrachloride (CCl4)-induced acute liver injury in mice, and whether oxidative stress and NLRP3 inflammasome activation participate in the process. The CCl4 mice model and controls were induced. The mice were treated with SSd at 1, 1.5, or 2.0 mg/kg in a total volume of 100 µl/25 g of body weight. Liver injury was assessed by histopathology. Oxidative stress was determined using mitochondrial superoxide production (MSP), malondialdehyde (MDA) content, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. NLRP3, ASC, and Caspase 1 were determined by real-time PCR and western blot. IL-1β and IL-18 levels were determined by ELISA. Significantly elevated oxidative stress was induced in the liver by CCl4, as demonstrated by histopathology and increases of MDA and MSP levels and decreases of SOD, GPx, and CAT activities (all P < 0.01). SSd significantly decreased the MDA and MSP levels and increased the activities of SOD, GPx, and CAT (all P < 0.05). The mRNA expression of NLRP3, ASC, and Caspase 1, and the protein expression of Caspase 1-p10, NLRP3, ASC, IL-1β, and IL-18 were significantly increased after CCl4 induction (all P < 0.01). These changes were reversed by SSd (all P < 0.05). Suppression of the oxidative stress and NLRP3 inflammasome activation were involved in SSd-alleviated acute liver injury in CCl4-induced hepatitis.

scholarly journals NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis

2019 ◽  
Vol 20 (14) ◽  
pp. 3466 ◽  
Author(s):  
Francesca Bonomini ◽  
Mariane Dos Santos ◽  
Francisco Veríssimo Veronese ◽  
Rita Rezzani
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Morphological Alteration ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

scholarly journals LncRNA Gm14205 induces astrocytic NLRP3 inflammasome activation via inhibiting oxytocin receptor in postpartum depression

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Jialei Zhu ◽  
Jing Tang
Keyword(s):  
Postpartum Depression ◽  
Nlrp3 Inflammasome ◽  
Oxytocin Receptor ◽  
Pathological Process ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation ◽  
New Strategy ◽  
Non Coding Rnas

Abstract Postpartum depression (PPD) is a kind of mental disorder characterized by persistent low emotions in puerperium. The most significant physiological change in postpartum is lactation which is regulated by oxytocin receptor (OXTR). However, whether OXTR is related to pathological process of PPD and the potential mechanism still remain unclear. In the present study, we prepared hormone-simulated pregnancy (HSP)-induced PPD mouse model and found that the protein level of OXTR in hippocampus of PPD model mice was down-regulated and Nod-like receptor protein 3 (NLRP3) inflammasome was activated. We identified five long non-coding RNAs (lncRNAs) related to PPD by transcriptome sequencing, including three up-regulated and two down-regulated. The five lncRNAs were associated with the signaling pathway of OXTR according to the bioinformatics analysis. Furthermore, we focused on one of the five lncRNAs, Gm14205, and found that it targeted OXTR which inhibited astrocytic NLRP3 inflammasome activation in hippocampal primary astrocytes. These findings illustrate that OXTR has protective effects in PPD by inhibiting NLRP3 inflammasome activation and provides a new strategy for targeting lncRNA Gm14205 in the pathogenesis of PPD.

scholarly journals Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Wenli Yu ◽  
Jingshu Lyu ◽  
Lili Jia ◽  
Mingwei Sheng ◽  
Hongli Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Hepatic Ischemia ◽  
Nlrp3 Inflammasome Activation ◽  
Hepatic Ischemia Reperfusion

Hepatic ischemia-reperfusion (HIR) has been proven to trigger oxidative stress and pyroptosis in the hippocampus. Sirtuin 3 (SIRT3) is an essential mitochondrial protein deacetylase regulating oxidative stress and mitophagy. Dexmedetomidine (Dex) has been demonstrated to confer neuroprotection in different brain injury models. However, whether the protective effects of Dex following HIR are orchestrated by activation of SIRT3-mediated mitophagy and inhibition of NOD-like receptor protein 3 (NLRP3) inflammasome activation remains unknown. Herein, two-week-old rats were treated with Dex or a selective SIRT3 inhibitor (3-TYP)/autophagy inhibitor (3-MA) and then subjected to HIR. The results revealed that Dex treatment effectively attenuated neuroinflammation and cognitive deficits via upregulating SIRT3 expression and activity. Furthermore, Dex treatment inhibited the activation of NLRP3 inflammasome, while 3-TYP and 3-MA eliminated the protective effects of Dex, suggesting that SIRT3-mediated mitophagy executes the protective effects of Dex. Moreover, 3-TYP treatment downregulated the expression level of SIRT3 downstream proteins: forkhead-box-protein 3α (FOXO3α), superoxide dismutase 2 (SOD2), peroxiredoxin 3 (PRDX3), and cyclophilin D (CYP-D), which were barely influenced by 3-MA treatment. Notably, both 3-TYP and 3-MA were able to offset the antioxidative and antiapoptosis effects of Dex, indicating that SIRT3-mediated mitophagy may be the last step and the major pathway executing the neuroprotective effects of Dex. In conclusion, Dex inhibits HIR-induced NLRP3 inflammasome activation mainly by triggering SIRT3-mediated mitophagy.

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