MICROBIAL PATHOGENESIS
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2023
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IF 3.8
Shun Wang,Xiaodi Jin,Hao Chen,Mingdong Han,Jiaxin Bao,Dong Niu,Yikang Wang,Rui Li,Zhiyong Wu,Jichang Li
Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo . Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.
研究领域:
兽医学
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药理学
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免疫学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiqi Huang,Yifan Su,Qianyu Wang,Mingxiao Feng,Dawei Zhang,Qian Yu,Chunyan Yan
Ganoderma lucidum spores are tiny mature germ cells ejected from the abaxial side of the pileus and were responsible for multiple pharmacological properties. The defatted G. lucidum spores are the byproducts after the extraction of G. lucidum spores oil by supercritical fluid extraction technology, which have not been given sufficient attention. In order to fully utilize the resources of G. lucidum spores, a glucomannan (SGL90–1, 6.4 kDa) was isolated from the defatted G. lucidum spores. SGL90–1 was composed of mannose, glucose, galactose, and fucose in a molar ratio of 23.9:28.7:9.0:1.0. The backbone of SGL90–1 was consisted of →2,4)- α -D-Man p -(1→, →6)- β -D-Man p -(1→, →2,6)- α -D-Man p -(1→, →2)- α -D-Glc p -(1→, and →3,6)- β -D-Glc p -(1 → with seven side chains, and terminated with β -D-Man p -(1→, β -D-Glc p -(1→, α -L-Fuc p -(1→, and β -D-Gal f -(1→. Moreover, SGL90–1 could significantly elevate the phagocytic capability of RAW264.7 macrophages and promote the levels of nitric oxide (NO), tumor necrosis factor- α (TNF- α ), and interlrukin-6 (IL-6) through activating the TLR4/MyD88/NF-κB signaling pathway. Collectively, these findings demonstrated the potential of SGL90–1 as a natural functional food with strong immune-enhancing effect.
研究领域:
真菌学
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免疫学
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药理学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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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.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Yi Zhao,Zi-Yan Hu,Ming Lou,Fu-Wei Jiang,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Shuo Liu,Yu-Sheng Shi,Hong-Mei Zhu,Jin-Long Li
Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.
研究领域:
毒理学
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胃肠病学
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分子生物学
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Guanghui Jiang,Bulei Wang,Yuwen Wang,Haoyue Kong,Yufei Wang,Peng Gao,Minghao Guo,Wenna Li,Jian Zhang,Zhezhi Wang,Junfeng Niu
Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides , with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide ( B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata . The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely →4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-2ace-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-3ace-Man p -(1→, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.
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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肝病学
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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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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DOI
PubMed
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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高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Yu Ling,Luo Qianwen,Rao Xiaohui,Xiao Xiao,Wang Pinghan
Kawasaki disease (KD) is a severe pediatric vasculitis leading to coronary artery complications. Hydrogen sulfide (H 2 S), a recognized endogenous gasotransmitter with anti-inflammatory properties, offers potential as a novel treatment for KD through its cardiovascular benefits. However, the specific effects and underlying mechanisms remain unclear. The objective of present study is to investigate the anti-inflammatory and therapeutic effects of exogenous H 2 S in KD using network pharmacology and experimental validation. By online database searches, a total of 405 pharmacological targets for H 2 S, 826 KD-related targets, and 107 potential therapeutic targets of H 2 S for KD were identified. Through PPI analysis and Cytoscape screening, 9 hub genes were filtered, namely TNF, IL6, JUN, AKT1, IL1B, TP53, NFKB1, MAPK1, and RELA. KEGG pathway enrichment indicated that the TLR4/MyD88/NF-κB signaling pathway may play a crucial role in the therapeutic effects of H 2 S on KD. Additionally, in vivo experiments confirmed that the treatment of sodium hydrosulfide (NaHS), an H 2 S donor, markedly improved body weight, reduced inflammatory pathology in the coronary arteries, and downregulated levels of inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, WB analysis confirmed that NaHS inhibited the expression of TLR4, MyD88, NF-κB, and p-NF-κB. In brief, it is the first to reveal that exogenous H 2 S attenuates the inflammatory response in KD via the TLR4/MyD88/NF-κB pathway, highlighting its potential as a novel therapeutic approach for KD. These findings lay a foundation for further development of H 2 S-based therapies for KD management.
研究领域:
儿科
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药理学
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免疫学
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心血管科学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1385
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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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产品关联
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PubMed
高影响因子
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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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
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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高影响因子
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