scholarly journals Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model

2018 ◽  
Vol 15 (3) ◽  
pp. 186-192 ◽  
Author(s):  
Qianchao He ◽  
Lingfei Jiang ◽  
Shanshan Man ◽  
Lin Wu ◽  
Yueqiang Hu ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hui Bai ◽  
Rui Yuan ◽  
Zhiheng Zhang ◽  
Lin Liu ◽  
Xinyu Wang ◽  
...  

Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 μg/L, 50 μL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 μL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1β and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.


2020 ◽  
Author(s):  
Liulong Zhu ◽  
Guoming Ding ◽  
Fan He ◽  
Maoqiang Li ◽  
Wu Jiang

Abstract Background: Neuronal loss, demyelination, and an excessive inflammatory response accompany the pathogenesis of spinal cord injury (SCI). The inflammatory response is promoted by inflammasomes in variety diseases. Dopamine is a neurotransmitter that also functions as a regulator in NLRP3 (nucleotide-binding oligomerization domain-like receptor 3) inflammasome-dependent neuroinflammation. However, the effects and molecular mechanisms underlying the role of dopamine in SCI are little known. Methods:Functional recovery was assessed using Basso Mouse Scale (BMS) and BMS subscore. Histopathologic damage was evaluated by H&E staining. Demyelination was evaluated using immunofluorescence staining of myelin basic protein. Neuronal loss was evaluated by immunochemistry staining of NeuN. Pyroptosis was assessed by flow cytometry, western blot, and cell viability and cytotoxicity assays.Results: This study using mice showed that dopamine was significantly associated with enhanced locomotor recovery after SCI; with a reduction in NLRP3 inflammasome activation, pyroptosis, neuron and myelin loss, and histological changes. In vitro data suggested an association between dopamine and suppressed NLRP3 inflammasome activation and neuronal pyroptosis, and greater survival of neurons. Conclusion: Thus, dopamine may be a novel and effective approach for improving recovery after SCI.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xue-mei He ◽  
Yan-zhen Zhou ◽  
Shuo Sheng ◽  
Jing-jie Li ◽  
Guo-qing Wang ◽  
...  

Neuroinflammation plays a crucial role in the pathological process of Parkinson’s disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of the NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasome activation could be an important breakthrough point on PD therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts, and other plant tissues with anti-inflammatory, antioxidant, and neuroprotective properties. However, the mechanisms underlying EA-mediated anti-inflammation and neuroprotection have not been fully elucidated. In this study, a lipopolysaccharide- (LPS-) induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. In addition, the DA neuronal MN9D cell line and microglial BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism. Results indicated that EA ameliorated LPS-induced DA neuronal loss in the rat substantia nigra. Further, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and subsequent proinflammatory cytokines’ excretion. Second, EA-mediated antineuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity were not shown upon microglial NLRP3 siRNA treatment. In conclusion, this study demonstrated that EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome activation.


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