BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Xin-Chun Zhang,Hong-Feng Liang,Xiao-Dong Luo,Hua-Jun Wang,Ai-Ping Gu,Chun-Ye Zheng,Qiao-Zhen Su,Jun Cai
Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia , the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.
研究领域:
神经科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
ACS Omega
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2019
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IF 2.584
Shanshan Wang,Qian Luo,Yuefang Zhou,Peihong Fan
The healthy benefits of hemp (Cannabis sativa L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2023
·Vol. 28
·期 8
·3482
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IF 4.6
Xingru Chen,Xiaolan Zhou,Xiaoqing Cheng,Liting Lin,Qi Wang,Ruoting Zhan,Qingguang Wu,Sijun Liu
In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1β (IL-1β). We further studied the mechanism of FA’s regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1β). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA’s inhibitory effects on TNF-α, IL-6 and IL-1β and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA’s inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases.Keywords:BV2 microglia;ferulic acid;autophagy;AMPK/mTOR signaling pathway;NLRP3 inflammasome;neuroinflammation
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2021
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IF 2.73
Shengyu Sun,Yourui Zou,Shaocai Hao,Zhanfeng Niu,Liang Wu
Objective Polydatin has been used in the treatment of various inflammatory diseases. However, its role in the regulation of neuroinflammation has not been reported. In this study, we designed to investigate the anti-inflammatory effects of polydatin in LPS-stimulated BV2 microglia cells.Methods Inflammatory mediators TNF-α, IL-1β, NO, and PGE2 production were measured by ELISA. The protein of signaling pathways were detected by western blot analysis.Results The results showed that polydatin significantly ameliorated the production of TNF-α, IL-1β, NO, and PGE2 up-regulated by LPS. Polydatin also blocked LPS-induced NF-κB activation. In addition, PI3K and AKT, the up-stream molecules of NF-κB signaling pathway, were inhibited by the treatment of polydatin. Also, we found the formation of lipid rafts was inhibited by polydatin through attenuating the cholesterol content. Finally, polydatin was found to increase the expression of ABCA1 and ABCG1.Conclusion In conclusion, the results of the present study suggested that polydatin exhibited its anti-inflammatory effects in BV2 cells through disrupting lipid rafts, which subsequently inhibiting PI3K/AKT signaling pathway.
研究领域:
药理学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
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2021
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IF 0.986
Wenyu Xin,Ming Jing,Junjie Yang,Meiling Wang,Guige Hou,Qiaoyun Wang,Leiming Zhang,Chunhua Wang
Emerging evidence indicates that NOD-like receptor protein 3 (NLRP3) inflammasome-induced inflammation plays a critical role in the pathogenesis of Parkinson’s disease (PD). Baicalein has been considered as a possible option for PD treatment based on its anti-neuroinflammatory effects. However, no studies have elucidated the precise mechanisms underlying the anti-neuroinflammatory activity of baicalein, particularly inflammasome-mediated effects. In this present study, rotenone-induced PD mice and BV2 microglia were used to investigate the anti-neuroinflammatory effects of baicalein and explore its underlying mechanism in vivo and in vitro. The results demonstrated that baicalein alleviated motor impairments and attenuated several inflammatory responses in rotenone-induced PD mice. Also, baicalein inhibited the expression of NLRP3 and activated caspase-1 in brain tissues. Correspondingly, baicalein prominently suppressed the inflammatory response in BV2 microglia induced by rotenone. Furthermore, in vitro data showed that baicalein suppressed the expression of NLRP3 and activated caspase-1 by abrogating the upregulation of ROS, as well as by inhibiting the TLR4/NF-κB signaling cascade. Overall, the results of the present study indicated that baicalein exerted anti-neuroinflammatory effects partly by inhibiting activation of the NLRP3 inflammasome, and targeting NLRP3 inflammasome signaling offers a novel therapeutic strategy for PD treatment.
研究领域:
神经科学
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药理学
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炎症
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Pan Su,Liming Liu,Yuhang Gong,Shuaijun Peng,Xiangli Yan,Ming Bai,Erping Xu,Yucheng Li
Background The pathogenesis of depression is largely influenced by dyshomeostasis of neuroinflammation regulated by microglia M1/M2 polarization, and NLRP3 inflammasome acts critical roles in shifting microglia polarization. Kaempferol (Kae), a major flavonoid in edible plants, possesses anti-inflammation and anti-depression capacity, but its underlying cellular and molecular mechanisms of antidepressive effect have not yet fully explored. Methods In vivo studies with lipopolysaccharide (LPS)-induced depressive mice were carried out to evaluate antidepressant effect of Kae. In vitro, BV2 microglia cell line stimulated by LPS along with IFN-γ to detect pharmacological effects of Kae on microglia polarization and NLRP3. Based on two depression-related GEO datasets (GSE54570 and GSE54568) and the potential targets of Kae obtained from GeneCards database, enrichment analysis and protein–protein interaction (PPI) network construction reveal potential therapeutic targets of Kae for depression. Then the precise antidepressant mechanisms of Kae were verified by western blot and immunofluorescent staining in vivo and vitro . Results Our results showed that Kae significantly improves LPS-induced depressive behaviors and alleviates neuroinflammation in prefrontal cortex. Moreover, Kae obviously shifted microglia polarization to M2 phenotype, and also suppressed NLRP3 in prefrontal cortex and BV2. Enrichment analysis and PPI network construction suggested PPARγ and STAT1 signaling are related to regulation of NLRP3 in depression. Furtherly, Kae remarkably enhanced PPARγ activation and inhibited nuclear translocation of p-STAT1 in microglia of prefrontal cortex and BV2. Importantly, pre-incubation with PPARγ antagonist T0070907 or overexpression with CA STAT1 (constitutively active STAT1) both prevented pharmacologic effects of Kae on shifting microglia polarization and suppressing NLRP3 in BV2. Noteworthily, T0070907 significantly blocked the inhibitory effect of Kae on STAT1 while overexpression with CA STAT1 abolished the effect of Kae on PPARγ activation in BV2. Above results suggested that pharmacologic effects of Kae on microglia polarization and NLRP3 are dependent on the balance of counter-regulatory PPARγ and STAT1 signaling. Conclusion Our results indicated that the shifting microglia polarization and suppression of NLRP3 via tilting the balance of PPARγ and STAT1 signaling may be the antidepressant mechanism of Kae, which provides a novel perspective for elucidating antidepressive effect of Kae.
研究领域:
药理学
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神经科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2021
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IF 2.466
Yujie Jia,Yu Tong,Lianqiu Min,Yanrong Li,Yan Cheng
NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.
研究领域:
神经科学
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND INDUSTRIAL HEALTH
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2024
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IF 1.7
Xingchang Sun,Xin Qin,Gaofeng Liang,Xuhong Chang,Huike Zhu,Jiahao Zhang,Dan Zhang,Yingbiao Sun,Sanwei Feng
With the widespread use of manganese dioxide nanoparticles (nano MnO2), health hazards have also emerged. The inflammatory damage of brain tissues could result from nano MnO2, in which the underlying mechanism is still unclear. During this study, we aimed to investigate the role of ROS-mediated p38 MAPK pathway in nano MnO2-induced inflammatory response in BV2 microglial cells. The inflammatory injury model was established by treating BV2 cells with 2.5, 5.0, and 10.0 μg/mL nano MnO2 suspensions for 12 h. Then, the reactive oxygen species (ROS) scavenger (20 nM N-acetylcysteine, NAC) and the p38 MAPK pathway inhibitor (10 μM SB203580) were used to clarify the role of ROS and the p38 MAPK pathway in nano MnO2-induced inflammatory lesions in BV2 cells. The results indicated that nano MnO2 enhanced the expression of pro-inflammatory cytokines IL-1β and TNF-α, elevated intracellular ROS levels and activated the p38 MAPK pathway in BV2 cells. Controlling intracellular ROS levels with NAC inhibited p38 MAPK pathway activation and attenuated the inflammatory response induced by nano MnO2. Furthermore, inhibition of the p38 MAPK pathway with SB203580 led to a decrease in the production of inflammatory factors (IL-1β and TNF-α) in BV2 cells. In summary, nano MnO2 can induce inflammatory damage by increasing intracellular ROS levels and further activating the p38 MAPK pathway in BV2 microglial cells.
研究领域:
神经科学
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毒理学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
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2022
·Vol. 87
·期 5
·2159-2172
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IF 3.693
Zhenzhu Zhu,Lipin Yang,Zhong Li,Qin Liu
Neurotoxicity seriously affects the normal function of the nervous system. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin widely distributed in plants. Using β -amyloid (A β ) transgenic Caenorhabditis elegans and cell models, the neuroprotective effect of C3G was examined. The results showed that C3G remarkably suppressed A β aggregation, enhanced antioxidant capacity, improved the sensitive capacity towards chemical compounds, and boosted the memory ability of C. elegans . There was no significant difference between preventive and long-term treatment groups at the same dosage of C3G. Given the rapid metabolism and oxidation of C3G in vivo, the antioxidative and anti-inflammatory activities of C3G, the metabolite cyanidin (Cy), oxidation products of Cy (OP), as well as protocatechuic acid (PCA) at the corresponding level in OP were compared by using lipopolysaccharide (LPS)-stimulated BV2 microglia cell model. The results indicated that C3G, Cy, and OP could prevent BV2 cells against LPS-induced inflammation and oxidative damage. There was no significant difference on antioxidative and anti-inflammatory activities among C3G, Cy, and OP at the same level. Notably, PCA at the corresponding concentration in OP exhibited limited antioxidative and anti-inflammatory activities. The results suggested that C3G could exert neuroprotective function through the metabolite Cy and its oxidation products by inhibiting inflammation and oxidative damage, and PCA was not the primary bioactive species in OP. Practical Application This study confirmed the neuroprotection of cyanidin-3-O-glucoside (C3G) in transgenic Caenorhabditis elegans . C3G, its metabolite cyanidin (Cy), and oxidation products of Cy (OP) alleviated both neuroinflammation and oxidative damage. It highlighted that C3G-rich foods could exert neuroprotective potential through their oxidation products, the constitution, and existence of OP in vivo need further study.
研究领域:
神经科学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Research Express
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2020
·Vol. 7
·期 1
·015413
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IF 1.929
Ruixia Hou,Yuxi Wang,Jiali Han,Yabin Zhu,Hua Zhang,Libing Zhang,Liping Li,Kui Xu,Guanglei Fu,Xianbo Mou,Xi Chen,Lu Yang,Lei Nie
Controllable regulation of cell behavior is one of the most important factors conducive to the restoration of tissue functions. Recently, various strategies have been developed using physical or chemical cues. Although these techniques are effective, the high cost and complex fabrication procedures impede their application. In this study, we used a low cost and simple strategy to fabricate PVA/silk fibroin composite hydrogels using a cyclic freeze-thaw method. With the increase of freeze-thaw cycles, the pore size of hydrogels decreased, the elastic modulus increased, and the swelling rate decreased. Furthermore, we chose two shapes of model cells, a spindle using bone marrow mesenchymal stem cells and smooth muscle cells, and a round shape using BV2 microglial cells. PVA/silk fibroin composite hydrogels inhibited the adhesion and proliferation of stem cells and muscle cells and changed their cell shape from spindle to round, maintained the initial round shape of BV2 microglial cells, and promoted the proliferation of BV2 microglial cells. These results demonstrate that PVA/silk fibroin composite hydrogels can be used as a novel hydrogel system to regulate cell behavior.
研究领域:
材料科学
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生物材料
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细胞生物学
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组织工程
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Xiao-yan Zou,Ren-ren Xie,Wei Li,Chun-ling Su,Yu-si Chen,Huang Tang
A series of 11-substituted sampangine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase. Their chelating ability and selectivity for Cu 2+ over other biologically relevant metal ions were demonstrated by isothermal titration calorimetry. Their blood-brain barrier permeability was also tested by parallel artificial membrane permeation assay. Among the synthesized derivatives, compound 11 with the strong anti-acetylcholinesterase activity, high blood-brain barrier penetration ability and high binding affinity to Cu 2+ was selected for further research. Western blotting analysis, transmission electron microscopy, DCFH-DA assay and paralysis experiment indicated that compound 11 suppressed the formation of Cu 2+ -Aβ complexes, alleviated the Cu 2+ induced neurotoxicity and inhibited the production of ROS catalyzed by Cu 2+ in Aβ42 transgenic C. elegans . Moreover, compound 11 also inhibited the expressions of proinflammatory cytokines, such as NO, TNF-α, IL-6 and IL-1β, induced by Cu 2+ + Aβ 1 – 42 in BV2 microglial cells. In general, this work provided new insights into the design and development of potent metal-chelating agents for AD treatment.
研究领域:
神经科学
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药理学
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分子生物学
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化学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2019
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IF 6.044
Hang Zhang,Jing Zhong,Qian Zhang,Degang Qing,Chunyan Yan
Coreopsis tinctoria is being widely cultivated in Xinjiang of China, whose consumption is known to prevent diabetes and neurodegenerative diseases. To elucidate the bioactive ingredients responsible for these benefits, the alkaline soluble crude polysaccharide (CTB) was isolated from C. tinctoria . In vitro experiments showed that the inhibition of α -amylase and α -glucosidase by CTB was 13407-fold and 906-fold higher than that by positive control, respectively. Then, a novel arabinogalactan, CTBP-1, was isolated and purified from CTB. Structural analysis showed that CTBP-1 possessed a 1,6-linked β - d -Gal p and 1,5-linked α - l -Ara f backbone with branches substituted at the C-3 position of the 1,6-linked β - d -Gal p , and the side chains included 1,5-linked α - l -Ara f , T-linked β - d -Gal p and T-linked α - l -Ara f . The inhibitory effects of CTBP-1 on α -amylase and α -glucosidase were 2.7 and 17.9 times that of acarbose, respectively. CTBP-1 could avoid indigestion and similar side effects. In addition, CTBP-1 remarkably inhibited the release of nitric oxide (NO), tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. In summary, CTBP-1 is a novel arabinogalactan with great potential as a treatment for type 2 diabetes and Alzheimer’s disease.
研究领域:
药理学
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生物化学
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分子生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）