INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Wenyao Yang,Juanzhu Han,Liping Zhang,Yunsong Sun,Yuchen Zhu,Yiyu Liu,Jingyu Chen,Xiaoyao Liao,Hui Liao,Weizhuo Xu,Yongbo Song
Skeletal muscle inflammation associated with sepsis has been identified as a critical pathological process contributing to metabolic dysfunction and poor clinical outcomes. Voltage-gated sodium channels (VGSCs) have been implicated in immune modulation; however, their specific roles in skeletal muscle inflammation remain poorly understood. In this study, the VGSC subtype Nav1.5 was investigated as a potential regulator of inflammation, and the therapeutic efficacy of a novel recombinant scorpion peptide, DKK678, was evaluated. An in vitro model using lipopolysaccharide (LPS)-stimulated C2C12 cells and an in vivo cecal ligation and puncture (CLP) model in septic mice were established. In both models, Nav1.5 expression was significantly upregulated in response to inflammatory stimuli, while Nav1.4 expression remained unchanged. The nuclear factor kappa B (NF-κB) signaling pathway was found to be activated, contributing to increased expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adhesion molecules (VCAM-1), and gap junction proteins (Cx43). Suppression of VGSC activity using lidocaine resulted in the inhibition of NF-κB phosphorylation and downregulation of inflammatory markers, while the expression of interleukin-10 (IL-10) and interleukin-4 (IL-4) were restored. Tetrodotoxin (TTX) treatment did not replicate these effects, suggesting Nav1.5-specific involvement. DKK678 was developed through bioinformatic design and molecular docking simulations, which predicted a stronger binding affinity and structural stability with Nav1.5 compared to Nav1.4. These predictions were validated through functional experiments. In vitro, DKK678 treatment dose-dependently inhibited LPS-induced NF-κB pathway activation and reversed abnormal expression of VCAM-1 and Cx43. In vivo, DKK678 significantly ameliorated CLP-induced skeletal muscle damage, suppressed inflammatory cytokine production, and improved tissue histopathology. Furthermore, the structural integrity of immune organs such as the thymus and spleen was preserved in DKK678-treated septic mice, with partial restoration of lymphocyte populations and organ indices. Notably, Nav1.5 expression was downregulated by DKK678, while Nav1.4 expression remained unaffected. These results demonstrate that Nav1.5 serves as a critical inflammatory modulator in skeletal muscle and immune tissues. Its upregulation was shown to drive NF-κB pathway activation and inflammatory cytokine production. By targeting Nav1.5, DKK678 was able to exert dual protective effects on both skeletal muscle and immune organs under septic conditions. The therapeutic potential of DKK678 was found to be comparable to that of dexamethasone (DEX) at high doses, without altering Nav1.4 expression. In conclusion, the present study provides new mechanistic insight into the role of Nav1.5 in skeletal muscle inflammation and identifies DKK678 as a promising peptide therapeutic that targets Nav1.5 to suppress NF-κB-mediated inflammatory injury. These findings suggest that Nav1.5 inhibition represents a viable strategy for the treatment of sepsis-associated myositis and related inflammatory disorders.
研究领域:
免疫学
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药理学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jiao Liu,Danye Niu,Yu Tang,Ruoheng Zheng,Yinyin Qin,Xiuqin Cheng,Shubo Pan,Jinfei Yuan,Xiaohua Shi,Jiao Yang
Background β-Hydroxy β-Methylbutyrate (HMB), derived from leucine, is known for its role in anti-oxidation and anti-inflammation. But, the application of HMB in IBD treatment is not fully understood, highlighting the requirement for further research. Purpose We aimed to examine the effects of HMB treatment on DSS-induced chronic colitis in mice and explore its underlying mechanisms. Methods To simulate colonic inflammation, a murine colitis model was generated by using DSS induction. Critical indicators such as body weight, colon length, disease activity index (DAI), and gross pathology were thoroughly monitored. Immunohistochemistry assay was conducted to assess the expression of Occludin and F4/80. Flow cytometry was employed to evaluate the expression levels of CD80 and CD86. qPCR was performed to measure cytokine expression (IL-6, IL-1β, TNF-α, IL-22, CXCL2, iNOS). RNA sequencing was carried out using bone-marrow derived dendritic macrophage cells (BMDMs). Results Our study indicates that HMB treatment substantially mitigated colonic damage in murine models of DSS-induced colitis, highlighting its anti-inflammatory potential. Notably, HMB significantly enhanced the expression of Occludin in these mice. Furthermore, HMB downregulated proinflammatory markers such as IL-6, IL-1β, and TNF-α as well as CXCL2 in the colon tissue. In vitro experiments also revealed that HMB reduced production of proinflammatory cytokines induced by DSS and suppressed the expression levels of CD80 and CD86 in macrophage cells. On a mechanistic level, we demonstrated the anti-inflammatory effects of HMB by reducing the phosphorylation of p-ERK and p-p65, thereby limiting cytokine production in both in vivo and in vitro settings. Conclusion These findings indicate that HMB possesses anti-inflammation against intestinal inflammation and may hold promise as a potential therapeutic candidate for IBD treatment. There's growing interest in combining traditional anti-inflammatory agents with supplements like HMB to improve outcomes in complex IBD cases. HMB's role in established muscle preservation and reduction of systemic inflammation as described in this study could make it a valuable adjunct in IBD therapy.
研究领域:
免疫学
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药理学
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消化病学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
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2025
·
IF 3
Jinlei Yun,Yindi Zhang,Hongyan Zhang,Fengkun Xiao,Yichun Wang,Peng Xu,Liping Qu
The members of Pleione (Orchidaceae) are popular worldwide for their ornamental appeal and medicinal properties. Pleione bulbocodioides , a CITES Appendix II-listed species, has been traditionally used in dermatological therapies but remains pharmacologically understudied. In this study, the in vitro anti-inflammatory effects of extracts from artificially cultivated P. bulbocodioides were investigated. We found the P. bulbocodioides extract (PE) significantly suppressed TNF-α/IFN-γ-induced expression of IL-6, IL-1β, CCL5, CCL8, CXCL8, CXCL3, and TMEM173 (STING) genes in both HaCaT cells and NHEKs. Transcriptomic analysis and Western blotting confirmed the inhibitory effects on STING/NF-κB signaling pathway of PE. And phytochemical characterization identified militarine and batatasin III as principal bioactive constituents responsible for STING/NF-κB pathway inhibition by PE. PE also demonstrated comparable anti-inflammatory efficacy in LPS-induced RAW 264.7 macrophages and SLS-irritated 3D reconstructed human epidermis. Thus, these findings indicate the potential of PE as a natural anti-inflammatory therapeutic or skincare ingredient for dermatological applications.
研究领域:
药理学
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植物学
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皮肤病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 6.7
Yihang Wu,Zixiu Liu,Zhenxiu He,Jumei Yi,Xingfang Qiao,Chunbin Tan,Yajing Xing,Yaobo Zeng,Dajian Yang,Junlin Yin,Baomin Fan,Guangzhi Zeng
Ulcerative colitis is a chronic inflammatory disease with a remitting-relapsing clinical course, it has evolved into a global burden given its high incidence worldwide. Cantharidin (CTD) derivatives are a class of compounds whose structures characterized with a 7-oxabicyclo [2.2.1]heptane core. Though potent cytotoxicity CTD and its derivatives showed, their clinical usage as anti-cancer drugs was limited by the toxicity in organs. In order to find new CTD analogues with good activity and lower toxicity, 21 CTD analogues with or without alkynyl substitution at C5 position of 7-oxabicyclo [2.2.1]heptane core were synthesized, some compounds showed better in vitro anti-inflammatory activity compared to CTD and norcantharidin (NCTD). Based on the structure-activity relationship results of in vitro experiment, analogue 3i was chosen for further study. Results from the acute toxicity in mice showed that 3i was hypotoxic with the single-dose MTD (maximum tolerated dose) for oral administration is over 1852 mg/kg, at least 35-fold lower than that of NCTD. Mechanism study indicated that 3i could potently inhibit TNF-α induced activation of NF-κB signaling by down-regulation the expression levels of phosphor- IKK, IκBα , and NF-κB p65 , and alleviated dextran sulfate sodium-induced colitis in mice. This study indicated that CTD analogues with alkynyl substitution at C5 position of 7-oxabicyclo [2.2.1]heptane core is a kind of new compounds with good anti-inflammatory activity and lower toxicity in vivo, and might be used as therapeutic agents for inflammatory diseases.
研究领域:
药理学
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炎症
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药物发现
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2017
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IF 2.956
Haiming Chen,Chuanjian Lu,Huazhen Liu,Maojie Wang,Hui Zhao,Yuhong Yan,Ling Han
Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD , and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment .
研究领域:
皮肤病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
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2025
·Vol. 20
·期 1
·1-22
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IF 5.7
Li Xueyan,Ding Lu,Li Zirui,Cao Zhenghua,Li Min,Yin Kai,Song Siyu,Cao Liyuan,Xia Qinjing,Wang Zihan,Zhao Daqing,Tong Xiaolin,Li Xiangyan,Wang Zeyu
Background Asthma is a chronic inflammatory airway disease that remains inadequately controlled by existing conventional treatments. A traditional Chinese medicine (TCM) formula of Yangke powder (yǎng ké sǎn-YKS) has demonstrated potential in alleviating asthma symptoms and reducing its acute exacerbation. Despite clinical evidence supporting its benefit, there is still insufficient understanding of the active compounds in YKS and their underlying mechanisms, which limits its broader clinical application. Objective This study aims to identify the key active ingredients in YKS and explore their mechanisms, particularly through the PI3K/AKT/NF-κB pathways, to provide a scientific basis for its application in asthma treatment. Methods We employed UPLC-Q-Exactive Orbitrap-MS to analyze YKS constituents, identified key ingredients, and explored asthma treatment mechanisms through bioinformatics, network pharmacology, Mendelian randomization, and molecular docking. The asthma model was evaluated using ovalbumin (OVA) and pulmonary function tests, while pathological examination was conducted using hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson trichrome stains. Concentrations of IgE, IL-4, and IL-5 were measured by ELISA, and protein and mRNA expressions were confirmed via qPCR, immunohistochemistry, and Western blot analysis. Results A total of 174 compounds were identified in YKS by UPLC-MS, with 49 detected in the bloodstream, indicating their role as active ingredients. Bioinformatics analysis revealed 353 asthma-related targets and 972 potential targets for YKS. Key targets such as AKT1, TNF, and IL1B were validated by molecular docking. Our studies indicated that YKS modulates asthma primarily through the PI3K/Akt and NF-κB pathways, improving airway resistance, reducing inflammation, mucus production, and airway remodeling, and decreasing Th2 cytokines and IgE levels. Conclusion This investigation identifies Kaempferol, Norephedrine, Cynaroside, Genistein, and Rutin as critical active ingredients in YKS, impacting key biomarkers such as AKT1, TNF, and IL1B. These substances effectively modulate the PI3K/AKT/NF-κB pathway, enhancing the management of allergic asthma.
研究领域:
药理学
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免疫学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Ji Yang,Peng Guo,Hongtao Luo,Xin Tang,Wei Liu,Xiaolin Ren
Background: Current therapeutic options for inflammatory bowel disease (IBD) remain suboptimal due to limited efficacy, significant side effects, and high relapse rates, necessitating novel treatment strategies. Lumefantrine, a clinically established antimalarial drug, emerges as a compelling repurposing candidate based on its putative anti-inflammatory activity, though its efficacy and mechanism in IBD remain unexplored.Methods: A murine IBD model was induced by 3% dextran sulfate sodium (DSS). Mice received oral Lumefantrine (20 mg/kg/day) for 7 days. Disease progression was monitored via disease activity index (DAI) scoring and histological analysis. Serum cytokines (IL-1β, IL-6, TNF-α) and colonic inflammatory mediators (Cox-2, iNos) were quantified by ELISA and qPCR. Tight junction proteins (Claudin-1, ZO-1) were assessed by immunohistochemistry and Western blot. Molecular targets were identified through computational docking and pull-down assays. Additionally, NF-κB signaling modulation was assessed in lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IEC-6 and NCM460) via Western blot analysis.Results: Oral administration of Lumefantrine significantly attenuated disease activity index (DAI) scores and restored intestinal barrier integrity through upregulation of epithelial tight junction proteins Claudin-1 and ZO-1. Treated mice exhibited reduced serum levels of IL-1β, IL-6 and TNF-α, along with decreased colonic expression of inflammatory mediators cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos). Computational and experimental approaches identified FLI-1 a transcription factor upregulated in IBD colon tissues as Lumefantrine’s direct binding target. This interaction mediated suppression of NF-κB signaling, specifically downregulating phosphorylation of IκBα and p65 in LPS-stimulated intestinal epithelial cells.Conclusion: Lumefantrine ameliorates experimental colitis through FLI-1-dependent inhibition of the NF-κB pathway, demonstrating high repurposing potential as an IBD therapeutic.
研究领域:
免疫学
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分子生物学
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药理学
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转化医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
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2019
·Vol. 17
·期 1
·138
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IF 2.468
Chang Liu,Yaohui Zhu,Zhenxiang Lu,Weina Guo,Bayaer Tumen,Yalan He,Chao Chen,Shanshan Hu,Kangzhi Xu,Yan Wang,Lei Li,Shenghe Li
Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.Keywords:Cadmium;acute liver injury;Nrf2;NLRP3;NF-κB;MAPKs
研究领域:
毒理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
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2025
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IF 1.4
Chanyu Wu,Xiaohan Wang,Xincan Li,Hexian Li,Qiuyue Peng,Xiaoxin Niu,Yutong Wu,Zhiying Wang,Zuoyong Zhou
Corynebacterium pseudotuberculosis , a zoonotic intracellular bacteria, is responsible for abscesses and pyogranuloma formation of the infected host, which is essentially a chronic inflammatory response. Tripartite motif-containing protein 21 (TRIM21) negatively regulates pro-inflammatory cytokines production during C . pseudotuberculosis infection, the mechanism of which remains unclear. This study found that C . pseudotuberculosis infection in macrophages induced phosphorylation of IκB and p65. TRIM21 interacted with IκBα by PRY/SPRY domain, stabilizes IκBα and negatively regulates IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. In addition, TRIM21 positively regulates the ubiquitination of IκBα via K48 linkage rather than K63 linkage in C. pseudotuberculosis -infected macrophages. In brief, our research confirmed that TRIM21 negatively regulates canonical NF-κB activation by interacting with IκBα and decreasing IκBα phosphorylation in macrophages during C. pseudotuberculosis infection. Preventing inflammation induced by C. pseudotuberculosis infection through regulation of the NF-κB pathway is a potential way to control this pathogen.
研究领域:
免疫学
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微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Rui Ge,Qikai Su,Jian Liang,Lu Zheng,Qing-shan Li,Li Tang
The identification of natural compounds with therapeutic efficacy for acute lung injury has consistently represented a critical area of research. Dulcitol, a natural product isolated from plants, is extensively used in the food and medical industries as a sweetener. Herein, we investigated whether dulcitol exerts an anti-inflammatory effect on LPS-induced acute lung injury (ALI) in mice. In our study, ICR mice were pretreated with dulcitol at dose of 6, 12 and 24 mg/kg for seven consecutive days, followed by intratracheally instilled with LPS (10 mg/kg) to induce acute lung injury. In vitro, RAW264.7 and A549 cells were incubated with LPS in the presence of dulcitol to investigate the anti-inflammatory activity and mechanism. The results demonstrated that dulcitol effectively inhibited the infiltration of inflammatory cells and reduced the excessive production of pro-inflammatory cytokines triggered by LPS to ameliorates acute lung injury in mice. Additionally, in vitro experiments indicated that dulcitol suppressed the release of NO, IL-6 and TNF-α while reducing mRNA expression levels of IL-1β, IL-6, COX-2, iNOS and TNF-α in RAW264.7 and A549 cells in a dose-dependent manner. Furthermore, dulcitol significantly decreased TLR4, MyD88, and TRIF levels and inhibited the translocation of NF-κB from the cytoplasm to the nucleus. Our finding suggested that dulcitol could serve as a protective agent against LPS-induced acute lung injury by inhibiting the TLR-4/NF-κB signaling pathway.
研究领域:
免疫学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Wenkai Nie,Xuan Zhao,Yan Zhang,Cheng Zeng,Huiwen Yang,Bing Liu
Objective Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that significantly impacts patients' quality of life. Chlorogenic acid (CGA), a polyphenol present in various dietary sources and plants, has been shown to reduce skin inflammation. However, its efficacy and mechanisms of action in AD have not been thoroughly investigated. This study aimed to evaluate the therapeutic effect of CGA on AD in mice and explored its mechanism. Methods To establish a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB) to evaluate the therapeutic potential of CGA. The anti-inflammatory effects of CGA were assessed by measuring IL-1β and IL-6 levels in TNF-α-stimulated HaCaT cells. The phosphorylation levels of PI3K, Akt, Akt1, NF-κB, and IκB-α were analyzed using Western blotting. Molecular docking was conducted to evaluate the binding affinity of CGA to Akt1. Results Topical application of CGA significantly reduced dermatitis scores, spleen index, epidermal thickness, mast cell infiltration, and skin fibrosis. CGA reversed DNCB-induced increases in IgE, histamine, TNF-α, IL-1β, IL-6, and IL-8 levels. Western blot analysis showed that CGA inhibited the PI3K/Akt and NF-κB signaling pathways. In vitro , CGA exerts its anti-inflammatory effects by inhibiting the Akt1/NF-κB pathway, and the Akt activator (SC79) can counteract this effect. Molecular docking and dynamics simulations suggest that CGA may inhibit Akt1 activity by interacting with specific residues (ALA-50, GLY-37, TYR-326, ASP-323). Conclusions CGA improves AD by inhibiting the Akt1/NF-κB pathway, suggesting its potential as a natural treatment for AD.
研究领域:
皮肤病学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Jing Yang,Yiwen Zhou,Jinsong Shi
Acute pancreatitis (AP) is a noninfectious inflammatory disease with high morbidity and mortality, which is characterized by severe inflammation and tissue necrosis. Cordycepin (CRD), derived from Cordyceps militaris , possesses anti-inflammatory effects and immunomodulation properties. Here, we investigated the protective effects of CRD on pancreatic injury and clarified potential mechanisms in AP model. There were established caerulein-induced AP and CRD pretreatment models in vivo and in vitro, as showed by serum enzymes, histopathological alterations and pro-inflammatory cytokines. Pretreatment with CRD notably downregulated the serum amylase and lipase levels and apparently reduced pancreatic histopathological alterations in AP mice. Meanwhile, the MPO staining confirmed that CRD pretreatment modulated the infiltration of neutrophils in AP mice. Furthermore, CRD markedly decreased the levels of pro-inflammatory factors (IL-6, IL-1β, and TNF-α) though inhibiting the activation of nuclear factor-κB (NF-κB) and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in AP mice. In pancreatic acinar cancer cell 266-6, CRD pretreatment decreased cholecystokinin(CCK)-induced inflammatory response was consistent with those in vivo. Mechanistically, CRD was also revealed to activate activated protein kinase (AMPK) and attenuated inflammation both in vivo and in vitro. On the whole, this study indicated that CRD protects mice from pancreatic inflammatory process and damage by suppressed NF-κB and NLRP3 inflammasome activation via AMPK, which probably contributed to the potential therapy for AP.
研究领域:
药理学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）