INFLAMMOPHARMACOLOGY
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2024
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IF 4.6
Weng Jiyu,Wang Ying,Tan Zekai,Yuan Yanghe,Huang Shiyuan,Li Zexi,Li Yiming,Zhang Lanyue,Du Zhiyun
Objectives Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. Methods The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. Results In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. Conclusion Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.
研究领域:
神经科学
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Pengfei Yan,Junchao Wang,Xiyu Zhao,Liangyu Wang,Jia Xu,Weijia Li,Weihong Min,Dan Wu,Chunlei Liu
QMDDQ is peptide derived from shrimp that ameliorates scopolamine-induced memory impairment. In this study, behavioral experiments in mice showed that QMDDQ could reduce the latency, number of working memory errors of the total distance moved, number of reference memory errors, number of traversals of the original platform, and escape latency in mice. QMDDQ decreased AChE vitality and increased ACh, DA, and 5-HT content. HE staining revealed that the cells in the hippocampal areas exhibited a tight tissue structure, neat arrangement, clear outline, and no cell necrosis in the QMDDQ group. Immunohistochemistry showed that, the expression level of Notch1 protein was reduced, and that of the antibody antigen complex was reduced in the QMDDQ group. Immunofluorescence staining showed a decrease in the number of GFAP and Iba-1 of QMDDQ group. TEM revealed that the mitochondrial cristae are intact and clear of QMDDQ group. QMDDQ decreased expression levels of Notch 1, STAT3, HES1, GFAP, and Iba-1 and activated Notch1 signaling via western-blotting. Pharmacokinetic studies have shown that QMDDQ can be stably absorbed into the bloodstream, with absorption occurring within 12 h and metabolism being completed within 24 h. This study establishes a theoretical basis for active peptides to ameliorate memory impairment and initiates the development of memory-enhancing functional foods.
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
高影响因子
PHYTOTHERAPY RESEARCH
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2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
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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疼痛研究
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Feng Zhang,Keqing Zhao,Tao Tang,Yan Deng,Yun Zhang,Shuo Feng,Pu Feng,Mengyuan Guo,Xiaohui Li,Juan Cen
Neuroinflammation is considered as an important mechanism of vascular dementia (VaD). Our primary study showed that the bisindole analogue (2-(2-(bis(5-chloro-1H-indol-3-yl)methyl)phenoxy)aniline, compound 4ae ) had great anti-inflammation in zebrafish. Rat model of permanent occlusion of the bilateral common carotid arteries (2-vessel occlusion, 2VO) was utilized to evaluate the neuroprotective effect of 4ae . Our results showed that 4ae treatment effectively reduced Iba-1 positive microglia cells in cerebral cortex and hippocampus after cerebral ischemia . Compared with the model group, neuroinflammation characterized by Interleukin (IL)-6 and tumor necrosis factor (TNF)-α, oxidative stress characterized by reactive oxygen species (ROS) and superoxide dismutase (SOD) were both improved significantly after treatment with 4ae. Moreover, 4ae treatment significantly reversed ischemia-induced ACE enhancement, while notably increased the level of ACE2. To further elucidate the role of 4ae on neuroinflammation, we investigated the effects of 4ae on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system . The results demonstrated that the expressions of CD11b, TNFα and IL-6 and the level of ROS were up-regulated after treatment with LPS. More importantly, 4ae was able to block the activation of BV2 by reducing ROS production and the expression of inflammatory cytokines. In addition, our results suggested that 4ae inhibited the inflammatory response mediated by microglia cells by inhibiting NF-κB. This anti-inflammatory effect on microglia may be a potential mechanism for the neuroprotective effect of 4ae in VaD.
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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痴呆症
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神经保护
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产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
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2023
·Vol. 29
·期 4
·1000-1011
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IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
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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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Yu Wang,Shanshan Zhao,Xu Liu,Yumin Zheng,Lei Li,Su Meng
Objective Autism is a neurodevelopmental disorder which significantly impacts the quality of people’s life. Oxytocin is a hormone impacting the social cognition and interpersonal trust. In this study, we aimed to explore the role of oxytocin in autism. Methods Autistic mice models were established by valproate . Animal behaviors were assessed by open field test, tail suspension test , marble burying test and three-chamber social interaction test. Oxidative stress was evaluated by the levels or activities of malondialdehyde , superoxide dismutase , glutathion peroxidase , reduced glutathione and reactive oxygen species . Inflammation was assessed by the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6. The number of activated microglia was detected by immunofluorescence with an Iba-1 antibody. Results Our results showed that oxytocin improved the behaviors of autistic mice, with less anxiety, depression and repetitive behavior , and ameliorated social interaction. Further study showed that the elevated oxidative stress and inflammation in autistic mice were alleviated after treatment of oxytocin. Conclusion Our study demonstrates that oxytocin treatment ameliorates autism in a mouse model, maybe through its modulation on oxidative stress and inflammation. It is indicated that oxytocin may beneficial to autism.
研究领域:
神经科学
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药理学
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行为科学
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免疫学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Yao Hua,Limei Zhou,Weidong Yang,Wenji An,Xiaolin Kou,Jian Ren,Hailang Su,Rong Chen,Zhengping Zhang,Jianjun Zou,Zhihong Zhao
Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+) - borneol , is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma . Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.
研究领域:
神经病学
·
药理学
·
实验性卒中研究
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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）