Food Bioscience
·
2025
·
IF 5.9
Cheng Ning,Cailing He,Ling Yan,Changhong Liu,Aijin Ma,Lei Zheng
The research aimed to investigate the underlying anti-inflammatory and antioxidative mechanisms of walnut-derived peptides in BV-2 microglia with H 2 O 2 -induced injury, and to further assess their neuroprotective properties against cognitive impairments caused by lipopolysaccharide (LPS) in mice. The findings indicated that both walnut-derived peptides NPFD and LDAF significantly inhibited ROS production in H 2 O 2 -injured BV-2 microglia and attenuated oxidative stress in BV-2 microglial cells via the Nrf2/keap1 signaling pathway. In addition, LDAF showed greater improvement in inflammatory than NPFD in H 2 O 2 -injured BV-2 microglia. Meanwhile, The MWM demonstrated that LDAF had the potential to mitigate memory impairments caused by LPS through normalizing the brain's inflammatory responses and reducing oxidative stress. And LDAF treatment improved neuronal cell morphology in the hippocampal region of mouse brain tissue and increased the number of Nissl bodies in neurons of injured mice. These results showed that LDAF was able to improve spatial cognitive ability in mice by reducing inflammation and oxidative stress.
研究领域:
神经生物学
·
分子药理学
·
免疫调节
·
氧化应激
·
神经退行性疾病
·
营养干预
·
信号转导
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2023
·Vol. 18
·期 4
·e0281189
·
IF 3.7
Yanzhuo Yang,Qingting Yu,Bin Li,Zuisu Yang,Shuai Zhang,Falei Yuan
Palmitic acid (PA) is considered a major contributor to the inflammation in many metabolic diseases; however, this role has been questioned recently for the complicated procedures in preparing PA-bovine serum albumin (BSA) complex. This study is aimed to evaluate the effect of PA-BSA complexing methods on cell viability and inflammatory responses of BV-2 cells. Three commercially available BSA brands and two types of solvents were compared for their effects on the expression of inflammatory cytokines. Three commonly used proportions of PA-BSA were tested for cell viability and inflammatory responses. We found that all the three types of BSA were proinflammatory. Both ethanol and isopropanol dampened inflammation except that 1% isopropanol treatment increased the IL-1β level by 26%. When reducing the BSA content in PA-BSA solutions from 3:1 to 5:1, a marked increase in cell viability (11%) was seen. To our surprise, reducing BSA content in PA-BSA solutions from 5:1 to 10:1 decreased cell viability by 11%. The 5:1 group exhibited the lowest inflammatory profile. Either PA-BSA or BSA alone increased the entry of LPS to the cytosol, which further caused pyroptosis. In summary, we found 5:1 (PA:BSA) to be the best binding ratio for studying inflammation in BV-2 microglia. The presence of LPS in the cytosol in the context of BSA might be the reason for confounding results from palmitate studies.
研究领域:
神经科学
·
免疫学
·
细胞生物学
·
代谢紊乱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Chongchong Liu,Jiangyan Sun,Xiaoming Shen,Shefang Li,Sha Luo,Na Chen,Yunke Zhang
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4–31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32–62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
研究领域:
神经病学
·
药理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Li Li,Ru Liu,Jing He,Jing Li,Juan Guo,Yun Chen,Ke Ji
Objective. Microglial BV-2 cells are activated in the brain following insomnia. Naringin (NAR) is a polymethoxylated flavonoid that is also commonly found in citrus fruits and is known for its antioxidant potential. However, the effect of NAR on microglial cells has rarely been studied in the brain of an organism after insomnia. This study aimed to investigate the effects and potential mechanisms of action of NAR on microglial cell activation and inflammation. Methods. BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066. With the exception of the control group, all groups were stimulated with LPS (1 μg/mL) for 6 h. CCK8 was used to quantify cell viability and a scratch test was performed to detect cell migration. The expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), nterleukin 10 (IL-10), and insulin like growth factor (1IGF-1) were measured by ELISA. Western blotting was performed to determine the levels of p-STAT3 and p-JAK. The Focalcheck™ Thin-Ring Fluorescent Microspheres kit was used to detect cell phagocytosis. Immunofluorescence was used to observe the expression of iNOS and arginase1 in BV-2 cells. Results. Compared with the control group, cell migration, cell viability, and the expression of IL-1β, IL-6, TNF-α, and iNOS were significantly increased in the model group, whereas the expression levels of IL-10, IGF-1, and arginase 1, as well as cell phagocytosis were reduced. With the increase in NAR concentration, cell migration, cell viability, the expression levels of IL-1β, IL-6, TNF-α, and iNOS decreased, while the expression of IL-10, IGF-1, and arginase 1 increased. Compared with the control group, p-STAT3, and p-JAK expression in the model group were significantly increased (P<0.05). Compared with the model group, the expression of p-STAT3 and p-JAK in the NAR, NAR + WP1066, and WP1066 groups was significantly decreased (). Conclusion. NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway.
研究领域:
神经科学
·
免疫学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2026
·
IF 5.5
Zhipeng Lu,Yang Long,Xiang Li,Le Zhang,Jie Bai
The clinical utility of morphine is limited by the development of tolerance and addiction. These processes are linked to neuroinflammation involved microglial responses. Thioredoxin-1 (Trx-1) is a crucial endogenous antioxidant with neuroprotective properties, and our previous work has shown that Trx-1 overexpression blocks morphine-induced conditioned place preference (CPP). However, the role of Trx-1 in morphine-induced microglial inflammatory responses remains unclear. Here, we investigated the effects and underlying mechanisms of Trx-1 overexpression on morphine-induced microglial pro-inflammatory shifts, both in the microglial cell line BV-2 and in the ventral tegmental area (VTA) of mice. In vitro, morphine treatment increased intracellular reactive oxygen species (ROS) in BV-2 cells, upregulated markers associated with microglial reactivity (IBA-1 and MHC-II), activated the NF-κB pathway (evidenced by increased p -IκBα and nuclear p65 translocation), and elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) while reducing the anti-inflammatory cytokine IL-10. Overexpression of Trx-1 via adenoviral transduction reversed all these morphine-induced effects. In vivo, using a CPP paradigm, we confirmed that morphine CPP was blocked in Trx-1 transgenic (TG) mice. Biochemical analysis of the VTA from these mice revealed that Trx-1 overexpression similarly attenuated morphine-induced upregulation of IBA-1, MHC-II, and pro-inflammatory cytokines, consistent with in vitro results. Mechanistically, co-immunoprecipitation assays demonstrated an endogenous interaction between Trx-1 and the mu-opioid receptor (MOR). Overexpression of Trx-1 significantly enhanced this interaction and was associated with increased MOR expression. These results reveal that overexpression of Trx-1 suppresses morphine-induced neuroinflammation by binding MOR and reducing ROS-driven NF-κB activation in microglia. This mechanism positions Trx-1 as a potential therapeutic target for improving the clinical safety and efficacy of opioid addiction.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Dan Li,Jiangping Xu,Yunyun Qin,Ningbo Cai,Yufang Cheng,Haitao Wang
Roflupram (ROF) is a novel phosphodiesterase 4 inhibitor. We previously found that ROF suppressed the production of pro-inflammatory factors in microglial cells; however, the underlying mechanisms are largely unknown. The present study aimed to elucidate the underlying molecular mechanisms of the anti-neuroinflammatory effects of ROF in lipopolysaccharide (LPS)-activated microglial cells and LPS-challenged mice. Treatment with ROF suppressed LPS-induced expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in BV-2 microglia cell line. Immunofluorescence and Western blotting analysis showed that ROF significantly inhibited the activation of microglia, as evidenced by decreased expression of ionized calcium binding adaptor molecule-1 (Iba1). Similar results were obtained in primary cultured microglial cells. ROF induced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Sirtuin 1 (Sirt1). Interestingly, the AMPK inhibitor, compound C, blocked the role of ROF in both the phosphorylation of AMPK and the expression of Sirt1 in BV-2 cells stimulated with LPS. More importantly, the Sirt1 inhibitor, EX527, abolished the inhibitory role of ROF on the production of pro-inflammatory factors, and reactivated BV-2 cells. In mice challenged with LPS, ROF improved cognition and decreased the levels of IL-6 and TNF-α in both the cortex and hippocampus. In contrast, EX527 weakened the effects of ROF on cognitive enhancement and reduction of pro-inflammatory factors in the cortex and hippocampus. Furthermore, EX527 blocked the inhibitory role of ROF in the activation of microglial cells in both the hippocampus and cortex. Taken together, our results indicated that ROF attenuated LPS-induced neuroinflammatory responses in microglia, and the AMPK/Sirt1 pathway is essential for the anti-inflammatory effects of ROF.
研究领域:
神经科学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2021
·Vol. 47
·期 2
·264-278
·
IF 3.996
Gao Tianyu,Gao Ce,Liu Zhidong,Wang Yun,Jia Xiaoxia,Tian Hao,Lu Qian,Guo Lin
Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3β), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca 2+ oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3β activator of pyrvinium. Moreover, an IP 3 receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca 2+ oscillation/Calcineurin/GSK-3β and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.
研究领域:
神经科学
·
药理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2023
·
IF 11.4
Dingbang Huang,Lixuan Chen,Qiuyi Ji,Yang Xiang,Qin Zhou,Kaiju Chen,Xiaoshun Zhang,Fei Zou,Xingmei Zhang,Zaihua Zhao,Tao Wang,Gang Zheng,Xiaojing Meng
Alzheimer's disease (AD) is a common neurodegenerative disease that is associated with multiple environmental risk factors, including heavy metals. Lead (Pb) is a heavy metal contaminant, which is closely related to the incidence of AD. However, the research on the role of microglia in Pb-induced AD-like pathology is limited. To determine the mechanism by which Pb exposure aggravates AD progression and the role of microglial activation, we exposed APP/PS1 mice and Aβ 1-42 -treated BV-2 cells to Pb. Our results suggested that chronic Pb exposure exacerbated learning and memory impairments in APP/PS1 mice. Pb exposure increased the activation of microglia in the hippocampus of APP/PS1 mice, which was associated with increased deposition of Aβ 1-42 , and induced hippocampal neuron damage. Pb exposure upregulated copper transporter 1 (CTR1) and downregulated copper P-type ATPase transporter (ATP7A) in the hippocampus of APP/PS1 mice and Aβ 1-42 -treated BV-2 cells. Moreover, Pb enhanced mitochondrial translocation of the mitochondrial copper transporter COX17, leading to an increase in mitochondrial copper concentration and mitochondrial damage. This could be reversed by copper-chelating agents or by inhibiting the mitochondrial translocation of COX17. The increased mitochondrial copper concentration caused by increased mitochondrial translocation of COX17 after Pb exposure may be related to the enhanced mitochondrial import pathway of AIF/CHCHD4. These results indicate that Pb induces the activation of microglia by increasing the concentration of copper in the mitochondria of microglia, and microglia release inflammatory factors to promote neuroinflammation, thus aggravating the pathology of AD. The present study provides new ideas for the prevention of Pb-induced AD.
研究领域:
神经科学
·
毒理学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Kai Wang,Shujie Zan,Jiachun Xu,Weiming Sun,Caixia Li,Wei Zhang,Daoyan Ni,Ruzhen Cheng,Lin Li,Zhen Yu,Linlin Zhang,Shuang Liu,Yuanwu Cui,Yulian Zhang
Background Aging is the primary risk factor for the onset of Alzheimer's disease (AD). Inflamma-aging is a major feature in the process of aging, and the chronic neuroinflammation caused by inflamma-aging is closely related to AD. As the main participant of neuroinflammation, the polarization of microglia (MG) could influence the development of neuroinflammation. Objective This study aims to observe the impact of YHD on microglia (MG) polarization and neuroinflammation to delay the onset and progression of AD. Methods In vivo experiment, four-month senescence accelerated mouse prone 8 (SAMP8) were used as the model group, the SAMR1 mice of the same age were used as the control group. In YHD group, 6.24 g/kg YHD was intragastrically administrated continuously for 12 weeks, and Ibuprofen 0.026 g/kg in positive control group. Morris Water Maze test was used to evaluate the learning and memory ability, Nissl's staining and immunofluorescence double staining for neuron damage and MG M1/M2 polarization, Enzyme-Linked Immunosorbent Assay (ELISA) for neuroinflammation biomarkers in hippocampus, Western blot for key protein expression of TREM2/NF-κB signaling pathway. In vitro experiments, 10 μM/l Aβ 1-42 induced BV-2 cell model was used to re-verify the effect of YHD regulating MG polarization to reduce neuroinflammation. Also, TREM2 small interfering RNA (siRNA) was used to clarify the key target of YHD. Results YHD could improve the learning and memory ability of SAMP8 mice evaluated by the Morris Water Maze test. Like Ibuprofen, YHD could regulate the M1/M2 polarization of MG and the levels of neuroinflammatory markers TNF-α and IL-10 in hippocampus, and relieve neuroinflammation and neuron loss. In addition, YHD could also regulate the expression of PU.1, TREM2, p–NF–κB P65 in the TREM2/NF-κB signaling pathway. Further in vitro experiments, we found that YHD had a significant regulatory effect on Aβ 1-42 -induced BV-2 cell polarization, and it could significantly increase PU.1, TREM2, decrease p–NF–κB P65, p -IKKβ, TNF-α, IL-6, IL-1β. At the same time, using siRNA to inhibit TREM2, it proved that TREM2 was a key target for YHD to promote Aβ 1-42 -induced BV-2 cell M2 polarization to reduce neuroinflammation. Conclusions YHD could regulate the TREM2/NF-κB signaling pathway through TREM2, thereby to adjust MG polarization and reduce AD-related neuroinflammation.
研究领域:
神经科学
·
药理学
·
中医药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2023
·
IF 3.3
Lu-Lu Lin,Gui-Jun Song,Hui Zhang,Yan Yin,Shi-Meng Xin,Li Ding,Yu Li
Alzheimer's disease (AD) is a serious neurodegenerative disease characterized by amyloid-β (Aβ) aggregation and neuroinflammation. G-protein-coupled receptor 34 (Gpr34) was found highly expressed in the hippocampus of APP/PS1 mice. However, its role in AD remains unclear. Herein, the role of Gpr34 as well as its molecular mechanism was explored. Data in GSE85162 were analyzed and the differently expressed genes in the hippocampus tissues of APP/PS1 mouse model of AD were subjected to GO, KEGG and GSEA enrichment analyses. APP/PS1 mice were used as an animal model of AD and the cognitive impairment was evaluated by a water maze test. The level of Gpr34 in hippocampus and BV-2 cells as well as the activation of ERK/NF-κB signal was determined by quantitative real-time PCR, western blot or immunofluorescence. Our results showed that, in BV-2 cells exposed to Aβ 1-42 , Gpr34 knockdown decreased the levels of TNF-α, IL-1β, IL-6 and iNOS and suppressed the activation of ERK/NF-κB signal. Moreover, the Gpr34-overexpression-induced activation of ERK/NF-κB signal and up-regulated levels of TNF-α, IL-1β, IL-6 and iNOS were abolished by FR180204, an ERK inhibitor. On the other hand, the in vivo study showed that Gpr34 knockdown ameliorated the cognitive impairment in APP/PS1 mice, decreased the levels of TNF-α, IL-1β and IL-6, the activation of microglia and ERK/NF-κB signal. In conclusion, Gpr34 knockdown relieved cognitive deficits in APP/PS1 mice and suppressed neuroinflammation and microglial activation, maybe via the ERK/NF-κB signal. It is indicated that the high level of Grp34 in hippocampus may contribute to the pathogenesis of AD.
研究领域:
神经科学
·
分子生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2024
·Vol. 68
·期 3
·4034
·
IF 2.1
Lan Wang,Zhenyu Fan,Haijin Wang,Shougui Xiang
Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT ‒ qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
·
药理学
·
炎症
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Li Ying-Qi,Chen Yi,Jiang Si-Qi,Shi Yuan-Yuan,Jiang Xiao-Li,Wu Shan-Shan,Zhou Ping,Wang Hui-Ying,Li Ping,Li Fei
Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl3-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins.
研究领域:
神经科学
·
药理学
·
分子生物学
·
生物信息学
✓ 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）