EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Hui Zhang,Qimei Yun,Zezhou Xu,Yifan Wang,Xianzhi Zhou,Ling Deng,Binsheng He
Neuroinflammation plays an essential role in neurological dysfunction in cerebral ischemia and reperfusion injury. Understanding the molecular network associated with neuroinflammation will provide potential targets for the neuroprotective treatment of ischemic stroke. An ischemia/reperfusion (I/R) rat model was established by middle cerebral artery occlusion (MCAO) and verified by laser speckle imaging and neurological function scoring. The ipsilateral cortex was analyzed using transcriptomic sequencing. The resulting transcriptomic dataset was combined with the ischemic stroke-associated C0948008 dataset from DisGeNet to screen differentially expressed genes (DEGs). Protein‒protein interaction (PPI) analysis was performed on DEGs associated with the inflammatory response. The candidate genes were verified using Western blotting or ELISA. I/R rats were subsequently treated with the TLR4 inhibitor TAK-242 to investigate the role of the TLR4/SYK/NF-κB pathway in neuroinflammation during ischemic stroke. A total of 264 genes were identified, most of which were enriched in inflammatory response pathways. PPI analysis of the DEGs associated with the inflammatory response revealed a total of three mutually interacting gene clusters, with TLR4, SYK, and NF-κB serving as the hub genes. The expression of proteins in the TLR4/SYK/NF-κB pathway and inflammatory cytokines significantly upregulated the I/R rats, whereas the trends were dramatically reversed by TAK-242. In addition, TAK-242 efficiently decreased the infarct area, improved neurological function, alleviated poststroke cognitive impairment (PSCI), recovered neuronal viability, and inhibited the overactivation of microglia and astrocytes. These data suggest that the TLR4/SYK/NF-κB pathway plays an important role in neuroinflammation and provide potential targets for neuroprotective therapy for ischemic stroke.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 8
·970
·
IF 8.2
Xiaofen Li,Yinju Zhang,Wenxia Dai,Ming Xia,Lang Zhou
Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce.Cinnamomum migaois a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and mechanisms remain largely unclear. This study investigated the efficacy and underlying mechanism ofC. migaoethyl acetate extract (MGE) against AMI. MGE significantly improved the viability of H9c2 cardiomyocytes subjected to OGD/R injured. UPLC-MS/MS and molecular networking identified 30 constituents in MGE, among which sesquiterpenoids predominated. In ISO-induced AMI rats, MGE dose-dependently mitigated myocardial injury, as reflected by reduced ST-segment elevation, serum CK-MB and LDH levels, and alleviated histopathological damage. MGE enhanced SOD and CAT activities, decreased MDA content, and inhibited the secretion of TNF-α, IL-6 and IL-1β. Mechanistically, MGE downregulated the expression of NOX4, HIF-1α, p38 MAPK and NF-κB p65, while activating the Nrf2/HO-1 pathway. Oxyphyllenone A and magnodelavin C were identified as key active sesquiterpenoids that stably bound to IL-17 and TNF. Collectively, MGE alleviates AMI injury via anti-oxidative, anti-hypoxic, and anti-inflammatory effects through modulation of the HIF-1α/Nrf2/NF-κB/MAPK axis downstream of oxidative stress, with sesquiterpenoids serving as its key bioactive components. This work provides robust experimental evidence supportingC. migaoas a promising natural antioxidant candidate for the prevention and treatment of AMI.
✓ 已验证
产品关联
DOI
高影响因子
NATURAL PRODUCT RESEARCH
·
2026
·
IF 1.8
Lin Zhang,Guanke Liu,Bingyang Zhang,Shiqing Song,Xiao Liu,Tie Yao,Feng Qiu,Feng Zhao
Two new secoiridoid glycosides, gentscaside A (1) and gentscaside B (2), were isolated along with three known compounds gentiopicroside (3), rindoside (4), gentiotrifloroside (5), from the Rhizomes of Gentiana scabra. The structures of the new compounds were determined by comprehensive NMR analysis, and their absolute configurations were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The five compounds were evaluated for their anti-inflammatory activity (NO inhibitory activity in LPS-stimulated macrophages). Compounds 1, 4 and 5 showed significant inhibitory effects on LPS-induced NO release in RAW 264.7 cells. The IC50 values are 2.15 μM, 3.02 μM and 6.87 μM, respectively. Additionally, the potential anti-inflammatory mechanism of the active new compound 1 was explored.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Shengyu Li,Yuting Pan,Gang Wang,Jintao Fang,Jingwei Wang,Youqi Ji,Zhenhao Dong,Ping Ling,Xianghou Zheng,Yao Gao,Qing Xia,Xia Liu,Wei Zhang
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by large-intestinal mucosal ulceration and persistent inflammation, which manifests as bloody diarrhea and abdominal pain and may elevate colorectal cancer risk. Polysaccharide-based hydrogels are attractive candidates for local rectal therapy of UC owing to favorable biocompatibility; however, their therapeutic performance is compromised by short lesion residence time caused by continuous intestinal peristalsis. Herein, we fabricated a muco-adaptive multifunctional hydrogel (B-ODT/CM@PF) constructed via dual-dynamic cross-linking of boronate-diol ester bonds and Schiff-base imine bonds for local treatment of UC. The carboxymethyl chitosan component contributes to rapid local hemostasis and epithelial barrier repair, whereas boron-complexed oxidized dextran confers broad-spectrum bactericidal capacity by disrupting bacterial membrane integrity. Benefiting from boronate-diol interactions, paeoniflorin (PF) is anchored within hydrogel networks to realize inflammation-triggered sustained release. The released PF targets the TLR4-NF-κB signaling axis to drive macrophage M2 polarization and mitigate excessive intestinal inflammatory responses. Moreover, B-ODT/CM@PF rescues the integrity of the intestinal mucosal barrier by inhibiting MLCK activation and preserving tight-junction proteins expression, further ameliorating colitis manifestations. Collectively, this dual-crosslinked bioadhesive hydrogel achieves synergistic functions including mucosal adhesion, hemostasis, antibacterial activity, immunomodulation and barrier reconstruction, providing a promising strategy for local treatment of UC.
✓ 已验证
DOI
高影响因子
BMC GASTROENTEROLOGY
·
2025
·Vol. 25
·期 1
·1-14
·
IF 2.6
Yuan Zuohui,Yang Xiaoping,Wang Xiaochun,Shi Xinlong,Chen Jia,Huang Lijun,Yang Jie,Shi Yuping,Zhang Liping,Mai Ping
Section
Background
This study aimed to investigate the effects of melatonin on diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore its potential mechanisms through modulation of the TLR4/MyD88/NF-κB pathway.
Section
Methods
Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D + melatonin 5 mg/kg (M-L), and IBS-D + melatonin 10 mg/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-κB proteins in colon tissue. Additionally, 16 S rRNA sequencing was used to analyze the composition of the intestinal microbiota.
Section
Results
Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.
Section
Conclusion
Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4/MyD88/NF-κB pathway and partial restoration of the intestinal microbiota.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Bingliang Zhou,Xiangshun Meng,Zhengying Yu,Bao Zhang,Wei Zhao,Lei Wang,Liang Peng,Jinhu Zou,Jingyu Chen,Xu Lin,Xuefeng Gao,Sheng-He Huang,Hong Cao
IntroductionIbeA is a critical virulence factor that is present in the GimA island in Escherichia coli (E. coli) K1, the most common cause of Gram-negative bacterial meningitis in newborns. IbeA has multiple virulence functions, including adhesion, invasion, and biofilm formation in the pathogenesis of E. coli K1 meningitis. However, it is unclear how IbeA coordinates its role in bacterial adhesion, invasion, and biofilm formation during crossing the blood-brain barrier (BBB).MethodsAn isogenic ibeA deletion mutant (ZD1) was generated from the neonatal meningitis–associated E. coli K1 strain E44. To define IbeA-mediated virulence, bacterial adhesion, invasion, and biofilm formation were quantified in human brain microvascular endothelial cells (HBMECs) using TEER, confocal imaging, and crystal violet assays. A neonatal rat meningitis model evaluated bacterial dissemination, BBB disruption, neuroinflammation, and neurological deficits. Mechanistic studies focused on Vimentin (VIM) dynamics using lipid-raft fractionation, cytoskeleton extraction, immunofluorescence, vimentin-knockout (Vim-KO) HBMEC and Co-immunoprecipitation to assess its redistribution, post-translational modifications, and interaction with NF-κB. The functional involvement of the IbeA–VIM–NF-κB signaling pathway was further examined by modulating VIM activity with glatiramer acetate (GA) in both in vitro and in vivo experiments.ResultsDeletion of ibeA and VIM significantly impaired bacterial adhesion, invasion, and biofilm formation both on HBMECs and on abiotic surfaces. In neonatal rats, infection with ZD1 resulted in higher survival rates, milder neurological symptoms, and a marked reduction of biofilm structures within the cerebral microvasculature compared with infection by the wild-type strain. IbeA-triggered post-translational modifications and cytoplasmic mobilization of VIM drive its nuclear translocation, which in turn activates NF-κB signaling. Pharmacological inhibition of VIM with GA disrupted IbeA-mediated virulence, lowering bacterial loads in the blood and alleviating neurological injury.ConclusionsIbeA is a key virulence factor that coordinates E. coli K1 adhesion, invasion, and biofilm formation by activating the VIM–NF-κB signaling pathway. Our study establishes for the first time a direct mechanistic link between IbeA’s multiple virulence functions through the above signaling pathway leading to acute BBB disruption and meningitis and identify GA as a potential drug development candidate for this disease.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Longqing Hu,Zhongyuan Yin,Songwei Tan,Yu Deng,Xincai Qu,Ting Hu,Qiong Wang
Triple-negative breast cancer (TNBC) derives only limited clinical benefit from radiotherapy (RT), partly due to abnormalities in the tumor microenvironment and dysregulated signaling pathways. By integrating TNBC cases from the METABRIC and TCGA cohorts, we implemented an analysis framework centered on RT-by-gene interaction terms, implicating TNF-α–NF-κB signaling and inflammatory response as potential effect modifiers of RT benefit. Based on a pathway-guided polyphenol–gene interaction screen, curcumin (Cur) was prioritized as a modulator of TNF-α–NF-κB/inflammation-related programs. We then engineered a multifunctional nanoplatform (TCC) that couples catalytic modulation of the tumor microenvironment with suppression of adaptive pro-survival programs. TCC was built on pH-responsive nanoceria (CeO 2 nanozymes) to modulate redox homeostasis and alleviate hypoxia, loaded with Cur, and coated with D-α-tocopherol polyethylene glycol succinate (TPGS) to improve stability and cellular uptake; cRGD was further introduced to generate cRGD-TCC for enhanced tumor targeting. In vitro and in vivo, TCC promoted G 2 /M-phase arrest, amplified RT-induced reactive oxygen species generation and DNA damage, and attenuated TNF-α–NF-κB/inflammatory programs and markers of inflammation, survival, and invasion. Collectively, TCC provides an integrated radiosensitization strategy that addresses microenvironmental barriers and adaptive tumor signaling, thereby potentially enhancing RT response in TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Wang Xin,Zhang Baokun,Chen Zhiheng,Shi Qiang,Yang Erzhu,Xu Jianguang,Lian Xiaofeng
After spinal cord injury (SCI), blood–spinal cord barrier (BSCB) disruption and hemorrhage lead to blood cell infiltration and progressive secondary injuries. Therefore, early restoration of the BSCB represents a key step in the treatment of SCI. Bazedoxifene (BZA), a third-generation estrogen receptor modulator, has recently been reported to inhibit inflammation and alleviate blood–brain barrier disruption caused by traumatic brain injury, attracting great interest in the field of central nervous system injury and repair. However, whether BZA can attenuate BSCB disruption and contribute to SCI repair remains unknown. Here, we developed a new type of biomaterial carrier and constructed a BZA-loaded HSPT (hyaluronic acid (HA), sodium alginate (SA), polyvinyl alcohol (PVA), tetramethylpropane (TPA) material construction) ( [email protected] ) system to effectively deliver BZA to the site of SCI. We found that [email protected] could significantly reduce inflammation in the spinal cord in SCI rats and attenuate BSCB disruption by providing covering scaffold, inhibiting oxidative stress , and upregulating tight junction proteins, which was mediated by regulation of the NF-κB/MMP signaling pathway . Importantly, functional assessment showed the evident improvement of behavioral functions in the [email protected] SCI rats. These results indicated that [email protected] can attenuate BSCB disruption via the NF-κB pathway after SCI, shedding light on its potential therapeutic benefit for SCI. Statement of significance After spinal cord injury, blood–spinal cord barrier disruption and hemorrhage lead to blood cell infiltration and progressive secondary injuries. Bazedoxifene has recently been reported to inhibit inflammation and alleviate blood–brain barrier disruption caused by traumatic brain injury. However, whether BZA can attenuate BSCB disruption and contribute to SCI repair remains unknown. In this study, we developed a new type of biomaterial carrier and constructed a bazedoxifene-loaded HSPT ( [email protected] ) system to efficiently treat SCI. [email protected] could provide protective coverage, inhibit oxidative stress, and upregulate tight junction proteins through NF-κB/MMP pathway both in vivo and in vitro , therefore attenuating BSCB disruption. Our study fills the application gap of biomaterials in BSCB restoration.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2023
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Kenan Zheng,Baojiang Lv,Lulu Wu,Chen Wang,Haoyou Xu,Xiaojun Li,Zhibing Wu,Yuanqi Zhao,Zequan Zheng
Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Heart Journal
·
2022
·Vol. 63
·期 3
·578-590
·
IF 1.823
Haibo Du,Lianqin Ding,Tian Zeng,Di Li,Li Liu
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）