Pharmaceuticals
·
2026
·Vol. 19
·期 2
·275
·
IF 5.7
Zhongnan Hu,Hui Liu,Weihua Wu,Tayyab Ali,Adam Junka,Farukh S. Sharopov,Xuan Zou,Shisong Fang,Yanfang Sun
Background: Influenza A virus is an acute respiratory virus that spreads quickly, affects a broad range of populations, and can lead to many complications and mortality.ArtemisiaL. species are widely used in traditional medicine, but their antiviral potential against H1N1 remains uncertain.Methodology: Network pharmacology and molecular docking were used to computationally explore their potential function in this domain, and to investigate how their invasion mechanisms and adsorption occur. UPLC-MS/MS analysis identified the main components of the extracts. The anti-H1N1 mechanism ofArtemisiaL. extracts was studied in vitro.Results: Network pharmacology identified 95 key targets betweenArtemisiaL. and IAV, with quercetin and luteolin as core active compounds. Molecular docking predicted strong binding affinities between these compounds and influenza virus proteins. UPLC-MS/MS analysis identified 75, 100, and 64 chemical components inACBE,AALE, andACTE, respectively, mainly flavonoids and terpenoids.ArtemisiaL. extracts exhibited both preventive and therapeutic effects against H1N1, reducing progeny virus NP mRNA and protein levels. In vitro experiments showed that higher concentrations of the extracts prevent virus attachment to MDCK cells by denaturing the HA protein. NA plays an essential role in progeny virus release. We found that a high concentration of ACTE can inhibit NA up to 85%, and ACBE showed a low inhibitory effect on NA.Conclusions: In terms of therapeutic effects,ArtemisiaL. extracts can regulate intracellular inflammatory factors via the TLR4/NF-κB/MyD88 signaling pathways and reduce the expression of IL-1β, IL-6, TNF-α, TLR4, NF-κB, p65, and MyD88 at the mRNA level, thereby inhibiting H1N1 virus replication. These results suggest that bioactive components inArtemisiaL. extracts may inhibit H1N1, potentially leading to the development of natural-product-based anti-influenza agents.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Tengteng Yuan,Shujie Lv,Wei Zhang,Yanan Tang,Hong Chang,Zihan Hu,Liang Fang,Jiaojiao Du,Sifan Wu,Xinli Yang,Yangfu Guo,Ruihan Guo,Zongrui Ge,Lei Wang,Caiyun Zhang,Rulin Wang,Weidong Chen
Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.
研究领域:
药理学
·
肝病学
·
分子生物学
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Qing Xia,Yuan Wei,Long-ji Hu,Fan-mei Zeng,Yu-wei Chen,Dan Xu,Yuan Sun,Lu-wei Zhao,Yi-fei Li,Guan-hua Pang,Wen Peng,Miao He
Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.
研究领域:
环境科学
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免疫学
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毒理学
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病理学
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PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Wang Hetong,Song Laiyu,Ju Wenhui,Wang Xuguang,Dong Lu,Zhang Yining,Ya Ping,Yang Chun,Li Fasheng
PM 2.5 is the main particulate air pollutant whose aerodynamic diameter is less than 2.5 micron. The inflammation of various respiratory diseases are associated with PM 2.5 inhalation. Pro-inflammatory cytokine IL-1β generated from effected cells usually plays a crucial role in many kinds of lung inflammatory reactions. The exacerbation of Th immune responses are identified in some PM 2.5 related diseases. To elucidate the underlying mechanism of PM 2.5 -induced acute lung inflammation, we exposed Balb/c mice to PM 2.5 intratracheally and established a mice model. Acute lung inflammation and increased IL-1β expression was observed after PM 2.5 instillation. Regulatory factors of IL-1β (TLR4/MyD88 signaling pathway and NLRP3 inflammasome) participated in this lung inflammatory response as well. Treatment with compound essential oils (CEOs) substantially attenuated PM 2.5 -induced acute lung inflammation. The decreased IL-1β and Th immune responses after CEOs treatment were significant. PM 2.5 may increase the secretion of IL-1β through TLR4/MyD88 and NLRP3 pathway resulting in murine airway inflammation. CEOs could attenuate the lung inflammation by reducing IL-1β and Th immune responses in this model. This study describes a potentially important mechanism of PM 2.5 -induced acute lung inflammation and that may bring about novel therapies for the inflammatory diseases associated with PM 2.5 inhalation.
研究领域:
免疫学
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呼吸医学
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环境健康
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PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2022
·
IF 6.073
Cui Huan,Zhang Cheng,Zhang Chunmao,Cai Zhuming,Chen Ligong,Chen Zhaoliang,Zhao Kui,Qiao Sina,Wang Yingchun,Meng Lijia,Dong Shishan,Liu Juxiang,Guo Zhendong
Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan in vivo, and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1β, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.
研究领域:
免疫学
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病毒学
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药理学
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分子生物学
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 1
·73
·
IF 4.5
Zhou Juan,Li Haipeng,Wen Ying,He Lingli,He Yangli,Meng Heng
Neuromyelitis optica spectrum disorder (NMOSD) is a rare but serious inflammatory demyelinating disease. A key characteristic of NMOSD is the presence of a pathogenic autoantibody in serum called aquaporin-4 immunoglobulin G (AQP4-IgG). This study investigates the mechanism of astrocyte-derived small extracellular vesicles (EVs) carrying mitochondrial DNA (mtDNA) to promote AQP4-IgG-induced microglial activation in neuromyelitis optica (NMO) via the toll-like receptor 9 (TLR9)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Serum IgG was isolated from NMOSD patients (AQP4-IgG) and healthy controls (Con-IgG). Astrocytes were treated with AQP4-IgG or Con-IgG. EVs were isolated via ultracentrifugation, characterized, and examined for internalization. Microglia were exposed to EVs, and mtDNA levels were assessed. An NMO mouse model was established, with neurological damage, mouse behaviors, tissue damage, and microglial characterization evaluated using modified neurological severity score, open-field test, rotarod test, luxol fast blue staining, and flow cytometry. Inflammatory cytokines, TLR9, MyD88, p65, IκBα, p-p65, and p-IκBα in BV2 cells and spinal cord tissues were analyzed via ELISA, RT-qPCR, and western blot. AQP4-IgG-induced astrocyte-derived EVs increased Iba1-high-expressing and CD86/tumor necrosis factor-α-high-expressing cells, reduced CD206/transforming growth factor-β-high-expressing cells, and boosted inflammatory responses. AQP4-IgG-induced EVs carried mtDNA to activate microglia via the TLR9/MyD88/NF-κB pathway. TLR9/MyD88/NF-κB pathway inhibition reversed AQP4-IgG-induced EVs’ promotion on microglial activation. In vivo, AQP4-IgG-induced EVs-mtDNA exacerbated microglial activation and NMO through the TLR9/MyD88/NF-κB pathway. AQP4-IgG-induced EVs carried mtDNA to upregulate TLR9, further activating the MyD88/NF-κB pathway, thereby promoting microglial activation and transition toward pro-inflammatory gene-high-expressing cells to drive NMO progression.
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FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Yanan Wang,Qianqian Wang,Gaigai Wang,Qiongqiong Zhang,Yongpeng Guo,Xin Su,Yu Tang,Matthew Koci,Jianyun Zhang,Qiugang Ma,Lihong Zhao
Zearalenone (ZEN) poses a potential threat on human and animal health partly through the nuclear factor (NF)-κB signaling pathway. In silico study suggested that rutin effective against TLR4 and NF-κB. A wetting test was designed to evaluate the effect and underlying mechanism of rutin in alleviating ZEN-induced inflammation in animals. Twenty-four female mice were randomly divided into 4 groups: control (basal diet), ZEN group (basal diet + ZEN), rutin group (basic diet + rutin), Z + R group (basal diet + rutin + ZEN). Results showed that rutin effectively alleviated ZEN-induced inflammation and damage of liver and jejunum in mice. Rutin addition reduced the content of lipopolysaccharide (LPS) in serum and liver mainly by improving the intestinal barrier function resulted from the production increase of short-chain fatty acids (SCFA). In sum, this study showed that rutin alleviated ZEN-induced liver inflammation and injury by modulating the gut microbiota, increasing the production of SCFA and improving intestinal barrier function, leading to the decrease of LPS in liver and the inhibition of MyD88 independent NF-κB signaling pathway in mice. Specifically, these findings may provide useful insights into the screening of functional natural compounds and its action mechanism to alleviate ZEN induced liver inflammation.
研究领域:
药理学
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毒理学
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分子生物学
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免疫学
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高影响因子
Food & Function
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2024
·
IF 5.1
Bufan Xu,Luyao Zhang,Di Wu,Zihe Qi,Juanjuan Cao,Wenrui Li,Lihua Fan,Yiheng Shi,Yongning Wu,Guoliang Li
Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.
研究领域:
环境科学
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毒理学
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微生物学
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免疫学
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水生生物学
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DOI
PubMed
高影响因子
GLYCOBIOLOGY
·
2014
·Vol. 24
·期 12
·1334-1342
·
IF 3.747
Zhang Wuxia,Mu Haibo,Dong Dongqi,Wang Dongdong,Zhang Amin,Duan Jinyou
Hyaluronic acid (HA) is an ubiquitous nonsulfated glycosaminoglycan of the extracellular matrix in all mammalian connective tissues. Along with the age growth, HA will lose its N-acetyl groups in vivo; however, the significance of this physiological process remains largely unknown. Herein, three highly N-deacetylated HAs (dHAs), dHA-5 kDa (Mw: 5 kDa, DD: 100%), dHA-16 kDa (Mw: 16 kDa, DD: 94%) and dHA-110 kDa (Mw: 110 kDa, DD: 72%), were generated after hydrazinolysis. Their capability in the activation of antigen-presenting cells (APCs) was compared with that of their respective HAs. Our results demonstrated that both HAs and dHAs could activate the nuclear factor-kappa B (NF-κB) transcription factor in APCs and induced cytokine production through the Toll-like receptor (TLR)/MyD88 pathway. Notably, the capacity of dHAs in cytokine induction was much lower than that of HAs. In addition, the TLR-2 pathway was much involved following the appearance of zwitterionic motifs in dHAs. Thus, our findings highlight that N-deacetylation renders HA divergences in immune response, which might be implicated in age-induced functional change in endogenous glycosaminoglycans due to the structural modification in vivo.
研究领域:
免疫学
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生物化学
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分子生物学
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老年医学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ruyi Chen,Fenfen Li,Kai Zhou,Mengyu Xing,Xiaoxi Zhang,Xinyu Zhao,Chenxi Wu,Ziwei Han,Yixuan Zhou,Li Yan,Daozong Xia
Ethnopharmacological relevance Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China. Aims of the study To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA. Materials and methods UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting . Results In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome. Conclusion MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.
研究领域:
药理学
·
中药学
·
网络生物学
·
分子生物学
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炎症研究
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PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zhixiang Cui,Hezhi Wang,Lu Qin,Ye Yuan,Jingwen Xue,Yalin An,Le Sun,Renfang Zhu,Qingyu Li,Yi Wang,Shuman Cui,Xuanguang Zhan,Qiyao Zhai,Haiyan Sun,Xin Zhang,Jian Guan,Chang Liu,Shirui Mao
The immunomodulatory effects and excellent tolerability of polysaccharides make them optimal candidates for pulmonary vaccine adjuvants. Yet, the structure–immunostimulatory activity relationship of polysaccharides remains unrevealed. Here, we developed nanovaccines decorated with four polysaccharides of distinct structures─hyaluronic acid (HA), pectin (PC), chondroitin sulfate (SC), and heparan sulfate (SH)─all sharing similar particle sizes and zeta potential. Polysaccharides containing sulfate groups (SC, SH) exhibited superior efficacy in overcoming natural inhalation barriers and recruiting dendritic cells (DC). DC stimulation assays revealed that HA and SH significantly upregulated the expression of costimulation signals, with IL-6 secretion rising over 8.7-fold compared to pure OVA. Fluorescence resonance energy transfer demonstrated their detachment within the lysosomal microenvironment, thereby enhancing antigen cross-presentation. However, in vivo findings only showed that SH upregulated CCR7 chemokine and swiftly migrated to lymph nodes. Molecular docking and Western blot analyses further elucidated the involvement of the TLR─MyD88─TRAF6─NF-κB/MAPK/IRF-7 signaling pathways. Notably, SH-modified nanovaccines induced a more robust cellular and humoral immune response with the potential for immune memory. This study confirms that sulfate groups in polysaccharides enhance immune activation and that combining sulfate with acetyl groups offers a promising adjuvant configuration for augmenting mucosal, cellular, and humoral immunity.
研究领域:
免疫学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yaming Yu,Ningning Mao,Lin Yu,Fangzhu Lin,Xiaofeng Shi,Xuanqi Lu,Yang Yang,Yu Lu,Deyun Wang
Ethnopharmacological relevance Endometritis is a common reproductive disease in dairy cattle after calving, characterized by persistent inflammation of the endometrium. YiMu-QingGong San (YMQGS), a patented Chinese medicine formulation, has demonstrated efficacy in the treatment of clinical endometritis in dairy cattle. However, the potential mechanisms by which YMQGS alleviates endometritis remain unclear. Aim of the study The objective of this study is to elucidate the underlying therapeutic mechanisms of YMQGS in the context of endometritis. Materials and methods The chemical components of YMQGS were analyzed using UHPLC/MS. The anti-inflammatory capabilities of YMQGS were assessed by inducing an inflammatory response in RAW264.7 cells with lipopolysaccharide (LPS). Moreover, a clinical model of endometritis was simulated via vaginal injection of LPS into the uterine horns to investigate the therapeutic mechanisms of YMQGS. Results YMQGS could downregulate the expression of inflammatory mediators (TNF-α, IL-6, IL-1β) by suppressing the activation of the TLRs/MyD88/TRAF6/NF-κB signaling pathway in RAW264.7 cells. Additionally, YMQGS facilitated the polarization of RAW264.7 cells towards M2-like macrophages (Mφs) while inhibiting M1-like Mφs polarization, thereby exerting anti-inflammatory effects. Further investigation revealed that YMQGS could diminish ROS production, augment cellular antioxidant capacity, preserve mitochondrial membrane potential, and reduce intracellular [Ca 2+ ]i accumulation, thereby minimizing cellular damage. In the mouse model of endometritis, YMQGS similarly inhibited the activation of the NF-κB signaling pathway in uterine tissues and modulated Mφ polarization in the endometrium, leading to a decrease in the expression of inflammatory factors and subsidence of the inflammatory response in the endometrium. Histological staining results showed that YMQGS reduced endometrial fibrosis, increased the expression of endometrial ZO-1, Occludin and glycoprotein, protect the endometrial barrier function, and prevent the further development of endometritis. Conclusion Collectively, the present study confirms that YMQGS possesses notable anti-inflammatory and antioxidant properties. The suppression of the NF-κB signaling pathway and the modulation of Mφ polarization emerge as the pivotal mechanisms by which YMQGS alleviates endometritis.
研究领域:
药理学
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免疫学
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生殖医学
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中医药
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PubMed
高影响因子
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