scholarly journals Gastrodin Alleviates Cognitive Dysfunction and Depressive-Like Behaviors by Inhibiting ER Stress and NLRP3 Inflammasome Activation in db/db Mice

2018 ◽  
Vol 19 (12) ◽  
pp. 3977 ◽  
Author(s):  
Tianyuan Ye ◽  
Xiangbao Meng ◽  
Ruiying Wang ◽  
Chenyang Zhang ◽  
Shuaibing He ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Er Stress ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Forced Swim Test ◽  
Inflammasome Activation ◽  
Diabetic Encephalopathy ◽  
Gas Treatment ◽  
Nlrp3 Inflammasome Activation

Patients with diabetes mellitus (DM) suffer more risks from diabetic encephalopathy such as cognitive dysfunction and depressive-like behaviors. Numerous studies show that ER (endoplasmic reticulum) stress and inflammation play important roles in the development of diabetic encephalopathy. Gastrodin (Gas), one major component of Gastrodia elata, is traditionally used in central nervous system disorders and is believed to possess anti-inflammatory, anti-apoptotic, and other neuroprotective effects. This present study aims to explore the protective effects of Gas on diabetic encephalopathy. Gas was administrated daily (70 and 140 mg/Kg) for 12 weeks. Meanwhile, the fasting blood glucose and body weight of db/db mice were measured every two weeks. After Gas treatment, the Morris water maze (MWM) test and novel object recognition (NOR) test were performed to assess the learning and memory functions of db/db mice, and the forced swim test was performed to evaluate depressive-like behaviors of db/db mice. Additionally, the expression of ER stress and Nucleotide binding and oligomerization domain-like (Nod) receptor family pyrin domain-containing 3 (NLRP3) inflammasome related proteins were evaluated by using Western blot. Our study suggested that Gas attenuated blood glucose levels and dyslipidemia of db/db mice. It has been shown that Gas could improve learning and memory function and depressive-like behaviors of db/db mice. Moreover, Gas inhibited ER stress and NLRP3 inflammasome activation in the hippocampus. Taken together, this study demonstrates that Gas attenuates the diabetic encephalopathy by inhibiting ER stress and NLRP3 inflammasome activation.

scholarly journals Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice

Molecules ◽  
2018 ◽  
Vol 23 (3) ◽  
pp. 522 ◽  
Author(s):  
Yadong Zhai ◽  
Xiangbao Meng ◽  
Tianyuan Ye ◽  
Weijie Xie ◽  
Guibo Sun ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Cognitive Disorders ◽  
Anxiety And Depression ◽  
Inflammasome Activation ◽  
Diabetic Encephalopathy ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

Diabetes is associated with a high risk of developing cognitive dysfunction and neuropsychiatric disabilities, and these disease symptomsare termed diabetic encephalopathy (DEP). Inflammation is involved in the development of DEP. The cleavage and maturation of the proinflammatory cytokine interleukin (IL)-1β is regulated by the NLRP3 inflammasome. Obese and type 2 diabetic db/db mice show anxiety- and depression-like behaviors and cognitive disorders associated with hippocampal inflammation. The purpose of this study was to explore the role of NLRP3 inflammasome in DEP. Results showed that expression levels of inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1, as well as IL-1β in the hippocampus of diabetic db/db mice were higher than those of non-diabetic db/m mice. Treatment of db/db mice with NLRP3 inflammasome inhibitor MCC950 ameliorated anxiety- and depression-like behaviors as well as cognitive dysfunction, and reversed increased NLRP3, ASC, and IL-1βexpression levels and caspase-1 activity in hippocampus. Moreover, MCC950 treatment significantly improved insulin sensitivity in db/db mice. These results demonstrate that inhibition of NLRP3 inflammasome activation may prove to be a potential therapeutic approach for DEP treatment.

Inhibition of NLRP3 inflammasome activation and pyroptosis with ethyl acetate fraction of Bungeanum ameliorated cognitive dysfunction in aged mice

2021 ◽  
Author(s):  
Meihuan Zhao ◽  
Yuan Dai ◽  
Ping Li ◽  
Jie wang ◽  
Tengyun Ma ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cognitive Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Ethyl Acetate Fraction ◽  
Inflammasome Activation ◽  
Material Basis ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Zanthoxylum Bungeanum ◽  
Zanthoxylum Bungeanum Maxim

Zanthoxylum bungeanum Maxim (Rutaceae), a homologous of medicine and foodstuff, has previously been demonstrated the potential prevention of age-related cognitive dysfunction. However, the mechanisms and material basis remain elusively understood....

scholarly journals Notoginsenoside R1 ameliorates diabetic encephalopathy by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

Oncotarget ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 9344-9363 ◽  
Author(s):  
Yadong Zhai ◽  
Xiangbao Meng ◽  
Yun Luo ◽  
Yongmei Wu ◽  
Tianyuan Ye ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Diabetic Encephalopathy ◽  
Nrf2 Pathway ◽  
Nlrp3 Inflammasome Activation

scholarly journals Empagliflozin Alleviates Diabetic Renal Tubular Lipid Accumulation and NLRP3 Inflammasome Activation Through AGEs-RAGE Pathway

2021 ◽  
Author(s):  
Zheng Liu ◽  
Juan Chen ◽  
Lili Sun ◽  
Jianzhong Li ◽  
Hong Sun
Keyword(s):  
Er Stress ◽  
Nlrp3 Inflammasome ◽  
Lipid Accumulation ◽  
Cholesterol Metabolism ◽  
Basal Diet ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Renal Tubular

Abstract Background: Advanced glycation end products (AGEs) are pathogenic factors of renal tubular lipid accumulation and play a negative role in diabetic kidney disease (DKD). Glucose cotransporter (SGLT) 2 inhibition offers strong renoprotection in the progression of DKD. The aim of the current study was to investigate the effects of empagliflozin (EMPA, a potent and selective SGLT2 inhibitor) on AGEs-induced renal tubular lipid accumulation in both diabetic mice fed with a high-AGEs diet and AGEs-treated cultured human renal proximal tubular epithelial (HK-2) cells. Methods: In vivo, EMPA was used to treat db/db mice fed a high-AGEs diet or an AIN-76 basal diet. In an in vitro study, HK-2 cells were treated with AGEs-bovine serum albumin (BSA) and/or EMPA. Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) translocation was detected by confocal microscopy. Results: EMPA reduced tubular lipid droplets and intracellular cholesterol content, as well as the expression of proteins involved in the synthesis and absorption of cholesterol in the kidneys of basal diet-fed db/db mice, high-AGEs diet-fed db/db mice and AGEs-BSA-treated HK-2 cells. AGEs-BSA loading promoted the formation of SCAP-SREBP-2 complexes and enhanced the transport of the complexes to the Golgi, but these effects were markedly inhibited by EMPA in HK-2 cells. EMPA reduced renal inflammation both in basal diet-fed db/db mice and high-AGEs diet-fed db/db mice, and suppressed NLRP3 inflammasome activation in AGEs-BSA-treated HK-2 cells. In addition, EMPA reduced the serum AGEs level in vivo and inhibited renal tubular endoplasmic reticulum (ER) stress and receptor of AGEs (RAGE) expression both in vivo and in vitro. Conclusions: EMPA attenuated AGEs synthesis and inhibited the AGEs-RAGE signaling pathway, thereby suppressing ER stress and inhibiting abnormal cholesterol metabolism and release of inflammatory cytokines, thus alleviating renal tubular lipid accumulation and inflammation.

scholarly journals ER stress induces NLRP3 inflammasome activation and hepatocyte death

2015 ◽  
Vol 6 (9) ◽  
pp. e1879-e1879 ◽  
Author(s):  
C Lebeaupin ◽  
E Proics ◽  
C H D de Bieville ◽  
D Rousseau ◽  
S Bonnafous ◽  
...  
Keyword(s):  
Er Stress ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Hepatocyte Death

scholarly journals Inhibition of IP3R/Ca2+ Dysregulation Protects Mice From Ventilator-Induced Lung Injury via Endoplasmic Reticulum and Mitochondrial Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Liu Ye ◽  
Qi Zeng ◽  
Maoyao Ling ◽  
Riliang Ma ◽  
Haishao Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lung Injury ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Ventilator Induced Lung Injury ◽  
Nlrp3 Inflammasome Activation

RationaleDisruption of intracellular calcium (Ca2+) homeostasis is implicated in inflammatory responses. Here we investigated endoplasmic reticulum (ER) Ca2+ efflux through the Inositol 1,4,5-trisphosphate receptor (IP3R) as a potential mechanism of inflammatory pathophysiology in a ventilator-induced lung injury (VILI) mouse model.MethodsC57BL/6 mice were exposed to mechanical ventilation using high tidal volume (HTV). Mice were pretreated with the IP3R agonist carbachol, IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) or the Ca2+ chelator BAPTA-AM. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected to measure Ca2+ concentrations, inflammatory responses and mRNA/protein expression associated with ER stress, NLRP3 inflammasome activation and inflammation. Analyses were conducted in concert with cultured murine lung cell lines.ResultsLungs from mice subjected to HTV displayed upregulated IP3R expression in ER and mitochondrial-associated-membranes (MAMs), with enhanced formation of MAMs. Moreover, HTV disrupted Ca2+ homeostasis, with increased flux from the ER to the cytoplasm and mitochondria. Administration of carbachol aggravated HTV-induced lung injury and inflammation while pretreatment with 2-APB or BAPTA-AM largely prevented these effects. HTV activated the IRE1α and PERK arms of the ER stress signaling response and induced mitochondrial dysfunction-NLRP3 inflammasome activation in an IP3R-dependent manner. Similarly, disruption of IP3R/Ca2+ in MLE12 and RAW264.7 cells using carbachol lead to inflammatory responses, and stimulated ER stress and mitochondrial dysfunction.ConclusionIncrease in IP3R-mediated Ca2+ release is involved in the inflammatory pathophysiology of VILI via ER stress and mitochondrial dysfunction. Antagonizing IP3R/Ca2+ and/or maintaining Ca2+ homeostasis in lung tissue represents a prospective treatment approach for VILI.

scholarly journals ER Stress Activates the NLRP3 Inflammasome: A Novel Mechanism of Atherosclerosis

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Xinnong Chen ◽  
Xiaochen Guo ◽  
Qihui Ge ◽  
Yixuan Zhao ◽  
Huaiyu Mu ◽  
...  
Keyword(s):  
Er Stress ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Ros Generation ◽  
Macromolecular Complex ◽  
Inflammasome Activation ◽  
Cellular Processes ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
The Unfolded Protein Response

The endoplasmic reticulum (ER) is an important organelle that regulates several fundamental cellular processes, and ER dysfunction has implications for many intracellular events. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is an intracellularly produced macromolecular complex that can trigger pyroptosis and inflammation, and its activation is induced by a variety of signals. ER stress has been found to affect NLRP3 inflammasome activation through multiple effects including the unfolded protein response (UPR), calcium or lipid metabolism, and reactive oxygen species (ROS) generation. Intriguingly, the role of ER stress in inflammasome activation has not attracted a great deal of attention. In addition, increasing evidence highlights that both ER stress and NLRP3 inflammasome activation contribute to atherosclerosis (AS). AS is a common cardiovascular disease with complex pathogenesis, and the precise mechanisms behind its pathogenesis remain to be determined. Both ER stress and the NLRP3 inflammasome have emerged as critical individual contributors of AS, and owing to the multiple associations between these two events, we speculate that they contribute to the mechanisms of pathogenesis in AS. In this review, we aim to summarize the molecular mechanisms of ER stress, NLRP3 inflammasome activation, and the cross talk between these two pathways in AS in the hopes of providing new pharmacological targets for AS treatment.

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