Journal of Neuroinflammation
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2026
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IF 11.5
Hanqi Wang,Yijun Chen,Junna Chang,Zhen Liu,Yang Yu
Depression is one of the most prevalent psychiatric disorders worldwide, yet its pathogenesis remains unclear. Here, we aimed to investigate the effects of formyl peptide receptor 2 (FPR2), a key regulator of innate immunity and inflammation, on lipopolysaccharide (LPS)-induced depression-related behaviors in mice after intraperitoneal administration, and to elucidate its regulatory mechanisms in microglia. FPR2 knockout (Fpr2 -/- ) significantly attenuated LPS-induced depressive and anxiety-like behaviors in mice. LPS markedly increased FPR2 expression in microglia of the prefrontal cortex (PFC) and hippocampus, while only a minimal increase was observed in neurons. FPR2 deficiency alleviated LPS-induced microglial activation and reduced neuronal synaptic alterations. RNA sequencing and validation experiments confirmed that FPR2 deletion substantially decreased LPS-induced microglial NLRP3 inflammasome activation and IL-1β levels in the brain. Mechanistically, FPR2 regulated downstream NLRP3 activation by modulating CSF1, and FPR2/CSF1 activation was governed by its upstream ligand, serum amyloid A (SAA). Analysis of public clinical datasets revealed that SAA1 levels were significantly upregulated in the orbital ventral PFC of patients with major depressive disorder (MDD) and in the plasma of patients with late-life depression. These findings demonstrate that the SAA/FPR2/CSF1/NLRP3 pathway mediates LPS-induced depressive-like behaviors by regulating microglial activation and neuroinflammation.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Junbo Chen,Shanquan Liang,Dan Liu,Shaoqing Yang,Qiaojuan Yan,Zhengqiang Jiang
2′-Fucosyllactose (2′-FL) shows promise in ameliorating metabolic disorders. However, the role of 2′-FL in metabolic hypertension (MH) remains unclear. This study aimed to evaluate the effects of 2′-FL on MH and explore its underlying mechanisms. 2′-FL treatment (1000 mg/kg) reduced systolic blood pressure (SBP) by 16.6% and alleviated dyslipidemia, microglial activation, and neuroinflammation in MH mice. 2′-FL markedly increased short-chain fatty acids (SCFAs)-producing beneficial bacteria, e.g., Akkermansia and Bifidobacterium by 3.9-fold and 19.5-fold, accompanied by increased fecal acetate and butyrate. Notably, the benefits of 2′-FL for MH were transferable via fecal microbiota transplantation (FMT). Particularly, 2′-FL-mediated attenuation of vascular dysfunction was associated with the inhibition of the lipopolysaccharide/toll-like receptor 4 (LPS/TLR4) signaling, a protective effect that could be transferred via FMT. The antihypertensive and metabolic benefits of 2′-FL in mice were accompanied by gut-brain axis modulation. These findings suggest that 2′-FL represents a promising dietary strategy for preventing hypertension-associated complications.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Teng Liu,Mingyan Yang,Yawen Yu,Xinxin Bai,Yaping He,Fei Yao,Yami Wu,Guangcan Zhou,Yanmei Wang,Dong Qi,Huaying Fan
Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid decline in kidney function, with inflammation being a key driver. In this study, the hydrophobic drug Rhein was conjugated to hyaluronic acid (HA) via esterification of its carboxyl group. The HA was then modified with 4-hydroxymethylphenylboronic acid pinacol ester (PBAP), which is responsive to reactive oxygen species (ROS). Finally, curcumin was loaded onto this construct to develop a ROS-responsive nanodelivery system (RHP@Cur). In vitro, the nanoparticles showed good ROS responsiveness in H 2 O 2 medium and successfully targeted the CD44 receptors on macrophages. Compared to curcumin alone, RHP@Cur significantly inhibited the secretion of NO and TNF-α and blocked NF-κB activation, with more pronounced effects. RHP itself also exhibited some anti-inflammatory effects. In an in vivo AKI model, the anti-inflammatory effects of RHP@Cur were consistent with the in vitro results. H&E staining results showed that RHP@Cur significantly improved kidney pathological damage. Immunohistochemical results revealed that it reduced the deposition of kidney injury molecule-1 (KIM-1) in the kidneys, with better effects than curcumin and RHP. These results suggest that Rhein exerts a synergistic anti-inflammatory effect, and its potential for combined use with curcumin for kidney therapy makes RHP@Cur more effective than RHP in treating AKI. In addition, since RHP@Cur delivers Cur, it enhances the therapeutic effect of Cur. Therefore, RHP@Cur provides a potential effective means for the treatment of acute kidney injury.
研究领域:
药物纳米技术
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炎症疾病研究
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药物递送系统
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急性肾损伤治疗
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生物聚合物化学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Zhen He,Xiangyun Tan,Ming Yuan,Liang Chen,Yan Meng,Qi Wang,Junjie Hu,Zhenpeng Qiu,Yuan Yang
Acute liver injury (ALI) is a prevalent form of hepatic disease associated with significant morbidity and mortality due to medical treatments, exposure to toxins or viral infections. Anethole trithione (ATT) is a heterocyclic sulfur compound recognized for its chemoprotective properties against cancer and drug-induced toxicity. This study aimed to evaluate the effectiveness of ATT in the treatment of ALI. The therapeutic effects of ATT on hepatic injury were evaluated in vivo by inducing ALI in mice through the administration of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Additionally, HepG2 and Huh7 cells exposed to LPS were utilized to investigate the underlying mechanisms in vitro. The results indicated that ATT significantly reduced the production of reactive oxygen species (ROS), mitigated oxidative stress-related biochemical markers, and inhibited hepatocyte apoptosis in vivo, resulting in marked improvement in ALI in the murine model. Mechanistic studies conducted both in vivo and in vitro demonstrated that ATT alleviates LPS/D-Gal-induced ALI by inhibiting ROS production and the activity of nuclear factor-kappa B (NF-κB). Collectively, these findings underscore the potential therapeutic benefits of ATT in the management of ALI.
研究领域:
药理学
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肝脏病学
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免疫学
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PubMed
高影响因子
Materials Today Bio
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2026
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IF 11
Bichao Lu,Jie Su,Yu Long,Xuefeng Liu,Tongfei Fu,Ningfeng Mao,Miao Wang,Wei Guo,Ke Yi,Shuhan Zhou,Wenliang Lv
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are severe respiratory diseases with a high mortality rate, characterized by pathological lung damage induced by excessive inflammation. Current therapeutic strategies for ALI are limited; conventional treatments are associated with severe side effects and lack targeted efficacy. Hesperetin(Hes)is a natural flavanone abundant in citrus fruits that exhibits promising anti-inflammatory potential, yet its further clinical application is hindered by poor solubility and low bioavailability. Small intracellular vesicles (sIVs) derived from mesenchymal stem cells have been demonstrated to possess the advantages of high yield, rapid cellular uptake and excellent stability. In view of this, the present study constructed a Hes-loaded sIVs-liposome nanodelivery system (sIVs-LPs@Hes) for the treatment of ALI via nebulized inhalation. Our findings revealed that sIVs-LPs@Hes could be efficiently absorbed and persistently retained in the lung, and it exerted a superior protective effect by inhibiting glycolysis through the MCU-mCa 2+ -NF-κB pathway, promoting M2 polarization of macrophages, ameliorating pulmonary inflammatory status, reducing pulmonary edema and repairing pathological lung damage. In conclusion, the present study not only elucidated the specific anti-inflammatory mechanism of Hes, but also developed a novel composite nanodelivery system by integrating the merits of sIVs and liposomes, thereby providing a promising potential therapeutic strategy for ALI.
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2016
·Vol. 41
·期 7
·1662-1672
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IF 2.472
Song Xiaoyu,Zhou Biao,Zhang Pingping,Lei Di,Wang Yubin,Yao Guodong,Hayashi Toshihiko,Xia Mingyu,Tashiro Shin-ichi,Onodera Satoshi,Ikejima Takashi
Silibinin, a flavonoid derived from the herb milk thistle ( Silybum marianum ), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1β and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS–BDNF–TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.
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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PubMed
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
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2023
·Vol. 69
·期 7
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IF 1.6
Jingmei Cao,Qing Zhao,Qing Jia,Yiming Li
Growing evidence suggested that long non-coding RNA (lncRNA) played a crucial role in the progression of ulcerative colitis (UC). Therefore, the purpose of this study is to understand how the lncRNA CBR3-AS1, which has been found to be up-regulated in UC, contributes to the bio-progression of the disease. To determine the concentration and relationship of the lncRNA CBR3-AS1, miRNA-145-5p, and FN1 in the LPS-induced Caco-2 model cells, qRT-PCR was employed in this study. Starbase was used to predict the target sites of the lncRNA CBR3-AS1 and the miRNA-145-5p, and Targetscan was used to predict the probable linking points of the FN1 and the miRNA-145-5p, which was confirmed by a twofold luciferase reporter test. The vitality of Caco-2 cells was determined using the CCK-8 and FCM tests. Using the ELISA kit, TNF, IFN, IL-6, and IL-17 were identified. The results of the experiment show that in Caco-2 cells treated with 10 ng/mL LPS, LncRNA CBR3-AS1 was up-regulated. Additionally, Caco-2 cells' LPS-induced apoptosis and inflammatory response were inhibited by lncRNA CBR3-AS1 inhibition. Dual-luciferase reporter experiments demonstrated that miRNA-145-5p and lncRNA CBR3-AS1 might connect. Moreover, miRNA-145-5p, which was shown to be poorly expressed in UC, was found to suppress inflammatory and apoptotic responses in Caco-2 cells activated by LPS. It's significant that FN1 was confirmed to be miRNA-145-5p's downstream target. Sh-CBR3-AS1's inhibitory effects were reversed by miRNA-145-5p knockdown, and the effects of the miRNA-145-5p inhibitor were reversed by sh-FN1. In conclusion, LncRNA CBR3-AS1 may offer a unique method for treating UC by suppressing the function of miRNA-145-5p, which is implicated in the development of UC.
研究领域:
分子生物学
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胃肠病学
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免疫学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Zheng Li,Haihua Feng,Yue Wang,Bingyu Shen,Ye Tian,Lin Wu,Qiaoling Zhang,Meiyu Jin,Guowen Liu
Rosmarinic acid (RA) has antioxidation, anticancer, antibacterial, anti-inflammatory and various biological functions. In our study, we aim to evaluate effects of RA on acute liver injury caused by LPS and d -galactosamine ( d -GalN) and its underlying molecular mechanism in mice. Our findings showed that RA could protect C57BL/6 mice from LPS/ d -GalN-induced acute liver injury, which not only reflected on declining aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the serum, but also restrained the phosphorylation of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK1/2) and p38 protein expression and the content of tissue myeloperoxidase (MPO) elevation. Moreover, RA could enhance the level of glutathione-dependent peroxidase (GSH-PX). Furthermore, RA promoted that nuclear factor erythroid-2-related factor 2 (Nrf2) transported into nucleus, and then up-regulated heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM) and quinone oxidoreductase (NQO1). These results indicated that RA could protect the mice from acute liver injury induced by LPS/ d -GalN.
研究领域:
药理学
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肝病学
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免疫学
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PubMed
高影响因子
Oncotarget
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2016
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IF 5.008
Dong Yang,Xinchuan Zheng,Ning Wang,Shijun Fan,Yongjun Yang,Yongling Lu,Qian Chen,Xin Liu,Jiang Zheng
Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells. By contrast, KB inhibited LPS internalization in Kupffer and RAW 264.7 cells. Loss of TLR4 did not affect LPS uptake into KB-treated hepatocytes. We also detected selective upregulation of the asialoglycoprotein receptor (ASGPR) upon KB treatment, and ASGPR colocalized with KB in cultured hepatocytes. Molecular docking showed that KB bound to ASGPR in a manner similar to GalNAc, a known ASGPR agonist. GalNAc dose-dependently reduced KB internalization, suggesting it competes with KB for ASGPR binding, and ASGPR knockdown also impaired LPS uptake into hepatocytes. Finally, while KB enhanced LPS uptake, it was protective against LPS-induced inflammation and hepatocyte injury. Our study provides a new mechanism for conjugated LPS hepatic uptake induced by the LPS neutralizer KB and mediated by membrane ASGPR binding.
研究领域:
免疫学
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肝病学
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药理学
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PubMed
高影响因子
BMC GASTROENTEROLOGY
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2023
·Vol. 23
·期 1
·1-10
·
IF 2.4
Xiang Ping,Ge Tingrui,Zhou Jingyi,Zhang Yonggang
Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1 , miR-142-5p, and nuclear receptor coactivator-3 ( NCOA3 ) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1 . Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1 -plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si- NCOA3 . Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.
研究领域:
分子生物学
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胃肠病学
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免疫学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
·
IF 2.5
Jiajia Pan,Lijun Meng,Rujun Li,Zicheng Wang,Wenjie Yuan,Yucheng Li,Lin Chen,Qinhao Shen,Weili Liu,Li Zhu
Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.
研究领域:
药理学
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心脏病学
·
分子生物学
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DOI
PubMed
高影响因子
IMMUNOBIOLOGY
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2024
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IF 2.5
Dan Gu,Ting Cao,Shijie Yi,Xiaoqian Li,Ya Liu
Background We have previously found that enhancer of zeste homolog 2 (EZH2) is correlated with inflammatory infiltration and mucosal cell injury in ulcerative colitis (UC). This study aims to analyze the role of X-inactive specific transcript (XIST), a possible interactive long non-coding RNA of EZH2, in UC and to explore the mechanisms. Methods C57BL/6N mice were treated with dextran sulfate sodium (DSS), and mouse colonic mucosal epithelial cells were treated with DSS and lipopolysaccharide (LPS) for UC modeling. The UC-related symptoms in mice, and the viability and apoptosis of mucosal epithelial cells were determined. Inflammatory injury in animal and cellular models were assessed through the levels of ACS, occludin, IL-1β, IL-18, TNF-α, caspase-1, and caspase-11. Molecular interactions between XIST, EZH2, and GABA type A receptor-associated protein (GABARAP) were verified by immunoprecipitation assays, and their functions in inflammatory injury were determined by gain- or loss-of-function assays. Results XIST was highly expressed in DSS-treated mice and in DSS + LPS-treated mucosal epithelial cells. It recruited EZH2, which mediated gene silencing of GABARAP through H3K27me3 modification. Silencing of XIST alleviated body weight loss, colon shortening, and disease active index of mice and reduced inflammatory injuries in their colon tissues. Meanwhile, it reduced apoptosis and inflammation in mucosal epithelial cells. However, these alleviating effects were blocked by either EZH2 overexpression or GABARAP knockdown. Rescue experiments identified caspase-11 as a key effector mediating the inflammatory injury following GABARAP loss. Conclusion This study suggests that the XIST-EZH2 interaction-mediated GABARAP inhibition activates caspase-11-dependent inflammatory injury in UC.
研究领域:
分子生物学
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免疫学
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胃肠病学
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PubMed
高影响因子
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