ENVIRONMENTAL POLLUTION
·
2021
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IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
研究领域:
毒理学
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环境科学
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分子生物学
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免疫学
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发育生物学
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高影响因子
INFLAMMATION
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2026
·Vol. 49
·期 1
·41
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IF 5
Zheng-qing Hu,Ruijie Ma,Hang Zhang,Jiahao Miao,Jia-qing Sun,Jinlong Yuan,Jiaqiang Liu,Zihuan Zhang,Dayong Xia
This study aims to elucidate the mechanism by which Heat Shock Protein 60 (HSP60) mediates microglial pyroptosis in the context of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and to investigate the effects of HSP60 inhibition on EBI after SAH. A mouse subarachnoid hemorrhage (SAH) model was established using prechiasmatic cistern blood injection. In vitro, microglia were stimulated with 25 µmol/L oxyhemoglobin (OxyHB) to simulate the SAH pathological environment. In vivo, mice received 100 mg/kg Mizoribine, while in vitro, 80 µmol/L Mizoribine was used to suppress SAH-induced HSP60 upregulation. Techniques including Western blotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, ELISA, modified Garcia neurological scoring, beam walking, brain water content measurement, Morris water maze, TUNEL staining, and Nissl staining were employed to systematically investigate the role of HSP60 inhibition in neuroinflammation and microglial pyroptosis after SAH. Compared to the sham group, both in vivo and in vitro studies with blinded, random sampling of six groups demonstrated a significant increase in HSP60 expression post-SAH. In vivo, 100 mg/kg Mizoribine alleviated blood-brain barrier disruption, cerebral edema, neuronal apoptosis/necrosis, and improved neurological deficits and cognitive impairment. In vitro, 80 µmol/L Mizoribine markedly attenuated microglial activation and pyroptosis, downregulated pro-inflammatory cytokines, and mitigated neuroinflammation. The upregulation of HSP60 after SAH promotes NLRP3 inflammasome assembly by activating the TLR4/MyD88/NF-κB signaling pathway, thereby inducing microglial pyroptosis and exacerbating the progression of early brain injury. Inhibition of HSP60 represents a potential therapeutic strategy for ameliorating EBI after SAH.
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Frontiers in Pharmacology
·
2020
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IF 4.225
Wei Aiwu,Xiao Huidongzi,Xu Guangli,Yu Xile,Guo Jingjing,Jing Zhuqing,Shi Shaoqi,Song Yanli
Anticardiolipin antibody (aCL), an important characterization of antiphospholipid syndrome, shows an intense association with vascular endothelial injury. Hyperoside is a flavonoid extracted from medicinal plants traditionally used in Chinese medicines, displaying anti-inflammatory, anti-cancer, and anti-oxidative properties in various diseases. Recent studies have shifted the focus on the protective effects of hyperoside on vascular endothelial injury. However, little is known about the mechanisms involved. In the present study, we investigated the effect of hyperoside on aCL-induced injury of human umbilical vein endothelial cells (HUVECs) in vitro. Our data illustrated that aCL induced HUVEC injury via inhibiting autophagy. Hyperoside reduced aCL-induced secretion of proinflammatory cytokines IL-1β and IL-8 and endothelial adhesion cytokines TF, ICAM1, and VCAM1 in HUVECs. Additionally, hyperoside activated autophagy and suppressed the mTOR/S6K and TLR4/Myd88/NF-κB signaling transduction pathways in aCL-induced HUVECs. To the best of our knowledge, this is the first study to investigate the effect of hyperoside on aCL-induced injury, as well as offer insights into the involved mechanisms, which is of great significance for the treatment of antiphospholipid syndrome.
研究领域:
免疫学
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药理学
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细胞生物学
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血管生物学
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高影响因子
Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1385
·
IF 7.5
Gong Jiaxin,Wei Feng,Wu Tianyu,Zhang Ningzhi,Zhang Yongqiao,Cui Zhaoqiang,Ge Junbo
Background Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. Methods Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipotoxicity model in AC16 cells was used to further confirm the protective effects of Fuc and its downstream signaling pathway against inflammation, pyroptosis and mitochondrial injury in vitro. Results In vivo, Fuc treatment alleviated obesity-related weight gain, hyperlipidemia, elevated systolic blood pressure and cardiac diastolic dysfunction. It also reduced the expression of pro-inflammatory cytokines and pyroptosis-related proteins, the level of oxidative stress, and mitochondrial abnormalities in the myocardium. Moreover, the vitro lipotoxicity model further confirmed the protective effect of Fuc. The molecular docking analysis identified TLR4 as the key target of Fuc. Fuc reduced the level of TLR4 and its downstream proteins MyD88 and p-NF-κB, while activating TLR4/MyD88/NF-κB pathway by TLR4 agonist Neoseptin3 reversed the protective function of Fuc in vitro. Conclusions These findings demonstrated that Fuc mitigated cardiac inflammation, pyroptosis and mitochondrial injury by inhibiting the TLR4/MyD88/NF-κB pathway, highlighting its potential as a therapeutic agent for obesity-associated cardiac injury.
研究领域:
心脏病学
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分子生物学
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免疫学
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代谢性疾病
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药理学
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NEUROSCIENCE LETTERS
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2026
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IF 2.2
Wuwei Xu,Yanxin Xu,Chunyan Yao,Xianmei Fu,Xiaoling Liu,Jinping Fan,Kexue Wang,Yumeng Zhou,Yuefei Li,Ting Hu,Yan Sai,Peng Luo,Tongjian Cai
T-2 toxin is a widely distributed environmental mycotoxin that poses severe neurotoxic risks to humans and animals. Neuroinflammatory responses constitute a key mechanism underlying the neurotoxicity of T-2 toxin. However, its molecular mechanisms for inducing inflammatory responses in the nervous system remain incompletely understood. This study investigated the role of B-cell translocation gene 2 (BTG2) in T-2 toxin-induced microglial activation and evaluated the neuroprotective potential of resveratrol (Res). In vivo experiments demonstrated that exposure to T-2 toxin resulted in spatial learning, memory impairments and locomotor deficits in mice. These behavioral phenotypes were accompanied by neuroinflammation in the hippocampus and cerebral cortex, characterized by microglial activation and the upregulation of BTG2. Res pre-treatment effectively reversed these neurobehavioral deficits and suppressed the neuroinflammatory response. Mechanistic analyses revealed that Res considerably alleviated T-2 toxin-induced TLR4/MyD88/NF-κB pathway activation. In vitro studies using BV-2 microglial cells confirmed these findings. Notably, siRNA-mediated knockdown of BTG2 also abolished TLR4 pathway activation and subsequent cytokine expression induced by T-2 toxin, establishing BTG2 as a critical upstream regulator. Furthermore, RNA sequencing systematically verified that BTG2 regulates the immune response network, specifically targeting the TLR4 cascades. Collectively, these findings provide novel evidence that Res may target the BTG2-regulated TLR4/MyD88/NF-κB signal pathway to exert neuroprotection, providing a promising intervention option for reducing the environmental and health hazards associated with exposure to T-2 toxin
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 20
·10073
·
IF 4.9
Mei Feng,Xinxiang Chen,Fan Huang,Lin Chen,Can Liu,Wei Li,Yinyan Li,Shaobin Chen,Zhen Deng,Zhengyi Wei,Yuan Luo,Xiyong Yu,Aiping Qin
Alpinetin, a distinctive plant-derived dihydroflavonoid from cardamom seeds, represents an under-explored chemical scaffold compared to common flavonoids like quercetin or kaempferol. While many flavonoids have shown general cardioprotective potential, the structural specificity of alpinetin may confer unique pharmacological advantages. Inspired by its historical use in traditional Chinese medicine for cardiac discomfort, this study systematically investigated its efficacy against acute myocardial infarction (AMI). In a rat AMI model, alpinetin demonstrated superior infarct size reduction and functional recovery relative to other tested flavonoids. It significantly attenuated key AMI pathologies—including inflammatory infiltration, CD68+ macrophage activation, IL-6/TNF-α release, collagen deposition, and cardiomyocyte apoptosis—more effectively than common flavonoid benchmarks. Mechanistically, alpinetin selectively targeted the TLR4/MyD88/NF-κB signaling axis with notable potency, a pathway not robustly modulated by other flavonoids in the screening. These findings not only validate the traditional wisdom of cardamom but also establish alpinetin as a structurally and mechanistically distinct flavonoid with high translational promise, offering a new candidate for the targeted treatment of ischemic heart disease.
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高影响因子
MOLECULES
·
2026
·Vol. 31
·期 11
·1933
·
IF 5.1
Yanlong Li,Anning Zhan,Xiaobing Zhang,Yu Duan,Jiawen Tang,Hua Bai,Qi Wang
Objective: The present study investigates the effect of 1,8-cineole on improving lipid metabolism disorder by regulating oxidative stress and inflammation via the TLR4/MyD88/NF-κB pathway. 1,8-Cineole is a monoterpene compound widely found in the essential oils of many plants and has been reported to possess anti-inflammatory and antioxidant activities. However, its role in regulating lipid metabolism disorders remains unclear. This study aimed to investigate the effects of 1,8-cineole on lipid metabolism and explore the potential mechanisms related to oxidative stress and inflammation. Methods: Cell viability was assessed by MTT assay to determine the optimal PA concentration for inducing lipid accumulation and the non-cytotoxic range of 1,8-cineole in HepG2 and AML-12 cells. Lipid droplets were visualized by Oil Red O staining, while triglyceride (TG) and total cholesterol (TC) levels were quantified using enzymatic kits. Oxidative stress markers (ROS by DCFH-DA fluorescence; MDA by TBA method; CAT activity by ammonium molybdate method) and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18 by ELISA) were measured. Western blotting analyzed key proteins in the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, p-P65, p-IκBα). Pathway-specific inhibitors were employed for mechanistic validation. Results: 1,8-Cineole (up to 1000 μg/mL) showed no cytotoxicity. It significantly attenuated PA-induced lipid droplet accumulation, reduced TG and TC levels (p< 0.05), and ameliorated oxidative stress by decreasing ROS and MDA while enhancing CAT activity in AML-12 cells (p< 0.01). Furthermore, 1,8-cineole suppressed pro-inflammatory cytokine release (TNF-α, IL-6, and IL-1β;p< 0.01), whereas no significant effect was observed on IL-18 levels. Downregulated TLR4/MyD88/NF-κB pathway activation. Inhibition of TLR4 or NF-κB mirrored these protective effects. Conclusions: 1,8-Cineole alleviates PA-induced lipid metabolism disorders, oxidative stress, and inflammation in hepatocytes, likely through suppression of the TLR4/MyD88/NF-κB signaling pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donglin Sui,Mingxin Li,Chunqing Ai,Shugang Li,Hong Chang,Yixuan Li,Shouhao Zhao,Huan Li,Xiaomeng Ren
This study aimed to investigate the therapeutic efficacy of Larimichthys Crocea Isinglass polysaccharide (CIP) in ameliorating DSS-induced colitis. CIP, a complex polysaccharide composed of six monosaccharides with a molecular weight of 3.97 kDa. Specifically, CIP treatment mitigated weight loss and histopathological damage in the colon, increased colon length, and by inhibiting the TLR4/MyD88/NF-κB pathway significantly downregulated the secretion levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, while simultaneously upregulating the anti-inflammatory cytokine IL-10 and inhibition of the oxidative stress-related enzyme inducible nitric oxide synthase (iNOS). Additionally, CIP treatment enhanced intestinal barrier function by increasing the expression of intestinal tight junction proteins (TJs) and MUC2, and it promoted the production of short-chain fatty acids (SCFAs). Concurrently, CIP modulated the composition of the intestinal microbiota, inhibiting the proliferation of potentially harmful bacteria such as Bacteroidota and Campylobacter . Taken together, these findings suggest that CIP exhibits promising attributes as a functional food constituent, with a particular efficacy in modulating and maintaining intestinal health.
研究领域:
免疫学
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营养学
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肠道健康研究
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Scientific Reports
·
2026
·
IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
·
IF 2.5
Zhen Yang,Huiying Li,Wei Zhao,Yingxia Yu,Yanling Lin,Jianxuan Liu,Xinghu Fan,Moyan Wang,Xin Teng,Zhikai Qiu
Objective Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. Methods The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. Results A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. Conclusion The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.
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JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Yiyang Du,Tingxu Yan,Bo Wu,Bosai He,Ying Jia
Ethnopharmacological relevance Increased inflammatory response and disruption of neuroplasticity are important mechanisms in the hypothesis of the pathogenesis of depression. Thus, these two aspects are conducive to the development of treatments for depression. Suanzaoren Decoction (SZRD) is a classic traditional Chinese medicine compound for the treatment of insomnia, which can clinically relieve depression symptoms, but its antidepressant pharmacological mechanism remains to be elucidated. Aim of this study Based on the hypothesis of inflammation and neuroplasticity in depression, this study aimed to investigate the antidepressant effect of SZRD and its specific molecular mechanism through chronic unpredictable mild stress (CUMS) induced SD rat model and lipopolysaccharide (LPS) induced BV2 cell neuroinflammation model. Materials and methods The body weight and behavioral indexes of CUMS model rats treated with orally or without oral SZRD for 4 weeks were detected. Hematoxylin and eosin staining was used to observe brain pathological damage. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was used to observe neuronal apoptosis. Immunofluorescence, ELISA kit and Western blotting were used to detect the inflammatory index Iba-1 and inflammatory factors, as well as the important inflammatory pathway TLR4/MyD88/NF-κB. Enzyme linked immunosorbent assay (ELISA) and western blotting were used to detect neuroplasticity indexes proteins-brain-derived neurotrophic factor (BDNF), presynaptic membrane protein-synaptophysin (SYP), and postsynaptic protein- 95(PSD95), and the key pathway Wnt/β-catenin. The possible mechanism of SZRD antidepressant was further explored in LPS-induced BV2 cells. Results In vivo and in vitro experiments showed that SZRD treatment significantly reversed the depression-like behaviors in rats, decreased the levels of inflammatory factors and increased the expression levels of BDNF, SYP, PSD95 in depression model rats. Furthermore, SZRD treatment inhibited the activation of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways and reduced the massive nuclear translocation of NF-κB and β-catenin. The addition of NF-κB pathway agonists could partially offset the inhibitory effect of SZRD on the Wnt pathway, and the addition of Wnt pathway agonists could also partially offset the inhibitory effect of SZRD on the TLR4 pathway. Conclusion This study suggestted that SZRD may exert its antidepressant effect by regulating TLR4/MyD88/NF-κB pathway and Wnt/β-catenin pathway in combination.
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FASEB JOURNAL
·
2025
·Vol. 39
·期 5
·e70439
·
IF 4.2
Yun Li,Site Yu,Jizhang Zeng,Situo Zhou,Xu Cui,Jie Zhou,Pihong Zhang
Excessive inflammation is a prominent issue in diabetic wounds, leading to delayed healing or amputation. Corilagin (Cori) is a natural polyphenolic compound with diverse pharmacological activities, particularly its anti-inflammatory properties. The aim of this study was to evaluate the anti-inflammatory effect of Cori on diabetic wounds and to explore the potential underlying mechanisms. The impact of Cori on wound healing was assessed in streptozotocin (STZ)-induced diabetic mice through morphological observation, histological staining, and gene expression analysis. Flow cytometry, qRT-PCR, western blot analysis, and RNA sequencing were conducted to elucidate the underlying mechanisms in RAW264.7 cells. The results demonstrated that Cori accelerated wound healing, inhibited excessive inflammation, and regulated macrophage polarization in diabetic mice. In Vitro, Cori decreased M1 polarization and inhibited the expression of pro-inflammatory mediators in RAW264.7 cells. Sequencing analysis revealed that Cori exerts anti-inflammatory effects on RAW 264.7 cells through multiple targeted mechanisms. Moreover, in LPS-induced macrophages, Cori dramatically decreased the activation of TLR4, MyD88, and NF-κB. Additionally, Cori enhanced M2 polarization by promoting fatty acid oxidation. In conclusion, the findings suggest that Cori modulates macrophage polarization through various targeted mechanisms, effectively suppressing inflammation and accelerating diabetic wound healing. Graphical Diabetic ulcers are common chronic wounds marked by excessive and persistent inflammation, imposing significant healthcare and economic burdens. Corilagin (Cori) was shown to accelerate wound healing in STZ-induced diabetic mice by modulating macrophage polarization and suppressing inflammation. In vitro, Cori inhibited M1 polarization and reduced the expression of pro-inflammatory mediators via the TLR4/MyD88/NF-κB pathway, while promoting M2 polarization by enhancing fatty acid oxidation. This study highlights Cori's potential as a therapeutic agent for diabetic wound management through its multi-targeted anti-inflammatory mechanisms.
研究领域:
药理学
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免疫学
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分子生物学
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糖尿病研究
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