MEDIATORS OF INFLAMMATION
·
2018
·
IF 3.549
Yiyi Jin,Jianchang Qian,Xin Ju,Xiaodong Bao,Li Li,Suqing Zheng,Xiong Chen,Zhongxiang Xiao,Xuemei Chen,Weiwei Zhu,Weixin Li,Wencan Wu,Guang Liang
Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Huangming Zhuang,Bin Li,Ting Xie,Changgeng Xu,Xunshan Ren,Fuze Jiang,Tianrun Lei,Panghu Zhou
Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation. Indole-3-aldehyde (3-IAld) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in multiple inflammatory diseases. However, the potential therapeutic role of 3-IAld in OA and the underlying mechanism remain to be explored. Methods IL-1β was utilized to induce chondrocytes inflammation. Then, cell counting kit-8 was carried out to assess the cytotoxicity of 3-IAld on rat chondrocytes viability. Meanwhile, RT-qPCR, Western blot, and immunofluorescence were performed to evaluate the expression of inflammatory factors, matrix-degrading enzymes and matrix synthesis protein, and the NF-κB pathway in chondrocytes treated with IL-1β alone, with 3-IAld or with siRNA-AhR. Results Our results showed that 3-IAld did not affect cellular viability at concentrations up to 50 μM. 3-IAld significantly inhibited the expression of pro-inflammatory cytokines (IL-6, iNOS and COX-2), and matrix-degrading enzymes (MMP3, MMP13 and ADAMTS5), upregulated the expression of matrix synthesis protein (aggrecan and collagen-II), and inactivated the NF-κB pathway in IL-1β-treated chondrocytes. However, AhR knockdown could totally abolish the aforementioned therapeutic capabilities and the inactivation of the NF-κB pathway induced by 3-IAld. Conclusions 3-IAld reduced inflammation through the AhR-NF-κB signalling pathway in IL-1β-induced chondrocytes, which is expected to provide a new therapeutic strategy for OA.
研究领域:
药理学
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免疫学
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骨科
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细胞生物学
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MOLECULAR NEUROBIOLOGY
·
2026
·Vol. 63
·期 1
·772
·
IF 5.5
Tian Xiaofeng,Liu Qing,Zhang Jiacheng,Du Huijiao,Wei Zhaoran,Sun Linjie,Gao Jiamin,Zhao Ruiting,Wang Lei,Zhang Yizhou
In recent years, the association between abnormal cholesterol metabolism and Parkinson’s disease (PD) has attracted considerable attention, but the specific mechanism remains controversial. First, we used Mendelian Randomization (MR) analysis to clarify the relationship between cholesterol and PD. Subsequently, scRNA-seq and RNA-seq were used to identify the crucial role of astrocyte 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in this process. Moreover, we verified its downstream target genes by RNA-seq, in vivo and in vitro experiments. The upstream transcriptional regulator of HMGCR was identified by database and validated by luciferase reporter and siRNA knockdown assays. The results of the MR analysis showed that low cholesterol levels may increase the risk of PD. This phenomenon was also observed in the PD mouse model. The scRNA-seq and RNA-seq results showed that astrocyte HMGCR played an important role in PD. Increasing astrocytic HMGCR alleviated cholesterol level and PD-related phenotypes. Mechanistically, astrocytic HMGCR-mediated cholesterol alleviated PD phenotypes by inhibiting Nuclear Factor Kappa-B (NF-κB) neuroinflammation. Furthermore, knocking down Forkhead Box O1 (FOXO1) restored HMGCR expression and cholesterol levels, subsequently inhibiting NF-κB activation. Our research indicated that the cholesterol synthesis disorder in astrocytes driven by HMGCR can exacerbate the pathogenesis of PD by promoting neuroinflammation. Targeting HMGCR in astrocytes will be a potential therapeutic approach.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Anming Zhu,Junxi Liu,Xianxian Cao,Jiahui Wu,Fengkun Xiao,Youyun Liu,Yanzhen Shen,Feifei Wang,Liping Qu
Pedunculoside as a TLR3-targeting immunomodulator for cheilitis-like inflammation treatment. • Pedunculoside has anti-skin inflammation and barrier repaire effects. • Pedunculoside inhibits the TLR3/TRIF/NF-κB signaling. • Pedunculoside provides a novel plant-assisted strategy for the treatment of cheilitis. Background Cheilitis is a lip-specific inflammatory disorder lacking safe long-term therapies. Topical glucocorticoids are limited by adverse effects, highlighting the need for plant-derived immunomodulators with dual anti-inflammatory and barrier-repairing effects. Objective To evaluate the therapeutic potential, mechanism and human efficacy of pedunculoside in cheilitis. Methods Pedunculoside was evaluated in vitro using CCK-8, scratch, ELISA, immunofluorescence, RT-qPCR, western blot, molecular docking and SPR. In human efficacy evaluation, pedunculoside formulation were assessed by VISIA-CR imaging, skin hydration and transepidermal water loss on the lips. Results Pedunculoside (≤120 μM) showed no cytotoxicity and increased scratch wound closure 4.5-fold ( N = 4). It upregulated barrier genes (AQP3: 1.7-fold, FLG: 2.3-fold, SPINK5: 11.16-fold, IVL: 7.96-fold, ZO-1: 2.26-fold, OCLN: 2.22-fold and KRT1: 4.41-fold) ( N = 4) and suppressed inflammatory cytokines (IL-6: 0.68-fold, IL-8: 0.53-fold, IL-1β: 0.65-fold, TSLP: 0.69-fold, CCL5: 0.55-fold and CCL17: 0.58-fold) ( N = 3). Mechanistically, pedunculoside directly bound with TLR3 and suppressed TLR3/TRIF/NF-κB signaling. In human efficacy, the pedunculoside formulation reduced lip redness by 0.3-fold (4 h, N = 32) and 0.23-fold (at 28 days, N = 20), decreased TEWL value by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) and improved hydration by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) versus baseline. Conclusion Pedunculoside is a novel TLR3-targeting immunomodulator that enhances barrier repair and suppresses inflammation in vitro, while its formulation improves cheilitis symptoms. The absence of animal studies before human testing represents a limitation; larger trials are warranted to confirm long-term safety and efficacy. Download: Download high-res image (372KB) Download: Download full-size image
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Balkan Medical Journal
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2026
·Vol. 43
·期 5
·253
·
IF 4.5
Ke Xu,Xiangyu Ren,Hongjie Cao,Tiantian Lyu,Zuisu Yang,Fangfang Huang
Background Bisphenol A (BPA), a widely used industrial chemical, is a well-known endocrine disruptor linked to testicular damage and impaired male reproductive function. Fucoxanthin (Fx), a marine carotenoid with potent antioxidant properties, has not been extensively studied for its potential to mitigate BPA-induced testicular injury. Aims To evaluate the protective effects of Fx against BPA-induced testicular injury and explored the underlying signaling mechanisms. Study Design Experimental study. Methods A mouse model of BPA-induced testicular injury was established. Transcriptomic analysis was performed to identify significantly altered genes. The therapeutic potential of Fx was assessed using combined molecular and histological approaches. Complementary in vitro experiments with TM3 Leydig cells were conducted to support the in vivo findings. Results Fx administration markedly attenuated BPA-induced disruptions in serum sex hormones, testicular histopathology, and proinflammatory cytokine levels. Ribonucleic acid sequencing revealed that Fx’s protective effects are associated with modulation of the nuclear factor kappa B (NF-κB), nucleotide-binding oligomerization domain-like, and Toll-like receptor signaling pathways. Validation experiments indicated that Fx inhibits nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and suppresses pyroptosis, accompanied by downregulation of key genes and proteins in the lipopolysaccharide/NLRP3 signaling cascade. In vitro analyses confirmed that Fx reduces oxidative stress and inflammation by inhibiting NF-κB activation and pyroptosis. Conclusion These findings suggest that Fx may serve as a promising dietary supplement or nutraceutical agent to mitigate the adverse reproductive effects of environmental endocrine disruptors, with potential benefits for male reproductive health.
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Urolithiasis
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2026
·Vol. 54
·期 1
·62
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IF 2.6
Sun Yan,Zhang Xiaoyu,Chen Xiaoyu,Zhao Jiawen,Liu Yunlong,He Weiyang
Paeoniflorin (PF) is a bioactive monoterpene glycoside with well-established anti-inflammatory properties; however, its therapeutic potential and molecular mechanism in nephrolithiasis remain insufficiently defined. In this study, network pharmacology was employed to predict potential targets of PF. In vitro, HK-2 cells exposed to calcium oxalate (CaOx) crystals were treated with PF to evaluate inflammatory responses, crystal adhesion, and NF-κB activation. A glyoxylic acid-induced mouse model was used to assess renal crystal deposition, renal function, and expression of key regulatory targets, supported by transcriptomic profiling. Molecular docking and molecular dynamics simulations were performed to analyze the interaction between PF and Serpine1, and functional relevance was further examined using exogenous Serpine1 rescue experiments. Integrated analyses indicated that PF exerts anti-nephrolithic effects predominantly through modulation of inflammation-associated signaling. PF dose-dependently suppressed CaOx-induced NF-κB phosphorylation and nuclear translocation, reduced the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and decreased crystal adhesion in HK-2 cells. In vivo, PF markedly attenuated renal crystal deposition, improved renal functional indices, and downregulated renal Serpine1 and IL-1β expression. Computational simulations supported a stable interaction between PF and Serpine1 (binding energy − 6.22 kcal/mol). Consistently, supplementation with exogenous Serpine1 partially reversed PF-mediated inhibition of NF-κB activation and cytoprotective effects. Collectively, these findings suggest that PF mitigates CaOx-associated renal injury by suppressing inflammation-centered signaling programs involving the Serpine1/NF-κB axis, thereby providing mechanistic insight into PF as a potential multi-target therapeutic candidate for nephrolithiasis.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Jinqi Hu,Jiexin Zhang,Xiaomei Ge,Suyu Li,Xudong Li,Tianrui Zhang,Xiang Li,Meng He,Guanbin Gao,Taolei Sun
SAA improves liver function and reduces fibrosis in a CCl 4 -induced mouse model. • SAA suppresses the phosphorylation of AKT1 in hepatic fibrosis. • SAA decreases inflammation and HSC activation by inhibiting the AKT1/NF-κB axis. • SAA might be a potential therapeutic agent for hepatic fibrosis. Hepatic fibrosis (HF) is a crucial and reversible stage, yet there is a paucity of effective clinical antifibrotic drugs. Salvianic acid A (SAA) has shown antifibrotic potential in preliminary studies; however, its molecular mechanisms and potential targets remain incompletely understood. To evaluate the therapeutic efficacy and mechanisms of SAA in mitigating HF, we employed a carbon tetrachloride (CCl 4 )-induced HF mouse model. In parallel, we used transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 cells and primary mouse hepatic stellate cells (HSCs) for in vitro studies. In CCl 4 -induced mice, SAA markedly improved liver function and suppressed HF, as evidenced by significant reduction in α-smooth muscle actin and collagen I expression and alleviation of inflammatory response. Similar antifibrotic and anti-inflammatory effects were observed in vitro . To investigate the targets and mechanism of SAA in HF, we employed network pharmacology, molecular docking, molecular dynamics simulations, and microscale thermophoresis. We found that SAA was predicted to interact with the allosteric pocket of RAC-alpha serine/threonine-protein kinase 1 (AKT1), accompanied by inhibition of AKT1 phosphorylation and the downstream nuclear factor-kappa B (NF-κB) signaling. To further explore the involvement of AKT1 in SAA's antifibrotic effects, we used the AKT activator SC79. In CCl 4 -induced mice, SC79 partly reversed the antifibrotic effects of SAA. Consistently, we observed that SC79 partially restored the inflammatory and fibrotic markers in TGF-β1-simulated HSCs, counteracting the inhibitory efficacy of SAA. Our findings suggest that SAA exerts antifibrotic effects in part through suppression of the AKT1/NF-κB axis and may represent a promising therapeutic candidate for HF. Download: Download high-res image (435KB) Download: Download full-size image
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Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
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2023
·
IF 2
Guanghong Shen,Chengjian Lou,Qunfeng Li,Bingxin Zhao,Yuhuan Luo,Fei Wu,Dian Jiao,Marong Fang,Yu Geng
Inflammatory injury following ischemia-reperfusion (I/R) severely limits the efficacy of stroke treatment. Edaravone dexborneol (C.EDA) has been shown to reduce inflammation following a cerebral hemorrhage. However, the precise anti-inflammatory mechanism of C.EDA is unknown. In this study, we investigated whether C.EDA provides neuroprotection after I/R in rats, as well as the potential mechanisms involved. A middle cerebral artery occlusion/reperfusion (I/R) model was created using Sprague-Dawley rats. The blood flow of the central cerebral artery was monitored by a laser speckle imaging system. The neurological score was used to assess behavioral improvement. Cerebral infarction volume was measured by TTC staining. And the integrity of the blood–brain barrier was detected by Evan's blue staining. The expression of the nuclear factor kappa-B (NF-κB)/ the NOD-like receptor protein (NLRP3) inflammasome signal pathway and microglia polarization were detected by immunofluorescence and Western blotting. The cerebral blood flow ratio indicates that the cerebral I/R model was successfully established. After reperfusion for 72 h, the improvement of neurological scores, infarct volume reduction, and integrity of the blood–brain barrier was observed in I/R rats with C.EDA treatment. Meanwhile, the immunofluorescence result showed that the expression of iNOS, NLRP3, and NF-κB protein was decreased and the level of Arg1 was increased. Western blot analysis showed that the expression of NF-κB/NLRP3 signal pathway-related protein was decreased. In conclusion, this study indicates that C.EDA alleviates I/R injury by blocking the activation of the NLRP3 inflammasome and regulating the polarization of M1/M2 microglia via the NF-κB signal pathway.
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Aging-US
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2020
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IF 4.831
Ke Lin,Wu Luo,Jueqian Yan,Siyuan Shen,Qirui Shen,Jun Wang,Xinfu Guan,Gaojun Wu,Weijian Huang,Guang Liang
Excessive vascular remodeling has been shown in hypertensive patients. In experimental models of hypertensive vascular injury, such as angiotensin II (Ang II) challenged mice, toll like receptor 2 (TLR2) initiates inflammatory responses. More recently, studies have reported atypical endothelial to mesenchymal transition (EndMT) in vascular injuries and inflammatory conditions. Here, we aimed to investigate whether TLR2 mediates Ang II-induced vascular inflammation and initiates EndMT. In a mouse model of angiotensin II-induced hypertension, we show that aortas exhibit increased medial thickening, fibrosis, and features of EndMT. These alterations were not observed in TLR2 knockout mice in response to Ang II. TLR2 silencing in cultured endothelial cells confirmed the essential role of TLR2 in Ang II-induced inflammatory factor induction, and EndMT-associated phenotypic change. Mechanistically, we found Ang II activates nuclear factor-κB signaling, inducing pro-inflammatory cytokine production, and mediates EndMT in both cultured endothelial cells and in mice. These studies illustrate a novel role of TLR2 in regulating Ang II-induced deleterious vascular remodeling through the induction of EndMT. The studies also suggest that TLR2 may be targeted to alleviate hypertension-associated vascular injury.
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Cell Death & Disease
·
2018
·Vol. 9
·期 7
·1-16
·
IF 5.638
Wang Zhe,Zhao Simeng,Song Lihua,Pu Yuzhi,Wang Qiang,Zeng Guangzhi,Liu Xing,Bai Ming,Li Shao,Gao Fabao,Chen Lijuan,Wang Chen,Tan Ninghua
Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1–TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.
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BIOCHEMICAL PHARMACOLOGY
·
2016
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IF 5.091
Shan Liu,Lingxin Zhu,Jie Zhang,Jingjing Yu,Xue Cheng,Bin Peng
Previous studies, including those from our laboratory, have demonstrated that the natural flavonoid isoliquiritigenin (ISL) is a promising agent for bone destructive diseases. However, the mechanisms underlying its anti-osteoclastogenic effects are still far from clear. Here, we evaluated the potential alterations of autophagy and nuclear factor-κB (NF-κB) during anti-osteoclastogenic effects by ISL in vitro and in vivo . We observed that ISL inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed autophagic microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 accumulation. ISL treatment resulted in the interruption of several specific features for autophagy in osteoclast precursors, including acidic vesicular organelle formation, LC3-II accumulation, and appearance of autophagic vacuoles. The RANKL-stimulated expression levels of autophagy-related genes and proteins also diminished in ISL-treated osteoclast precursors. The reactivation of autophagy by rapamycin almost reversed the ISL-elicited anti-osteoclastogenic effects. Interestingly, ISL inhibited the RANKL-stimulated NF-κB expression and nuclear translocation, whereas the NF-κB inhibitor Bay 11-7082 markedly suppressed the RANKL-induced autophagic activation. Consistent with the in vitro results, the administration of ISL could attenuate osteoclastogenic cathepsin K , autophagic LC3, and NF-κB expression to protect against inflammatory calvarial bone erosion in vivo . Our findings highlight the inhibition of NF-κB-dependent autophagy as an important mechanism of ISL-mediated anti-osteoclastogenic activity.
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IMMUNOLOGY LETTERS
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2025
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IF 2.8
Rui Kong,Jun Bai,Qing Yao,Xiaoqing Xu
Allergic asthma is characterized by persistent chronic airway inflammation, leading to mucus hypersecretion and airway hyperresponsiveness. Dual-specificity phosphatase 14 (DUSP14), a member of the DUSP family, is a key regulator in various biological processes. However, the function of DUSP14 in allergic asthma remains to be elucidated. In this study, we aim to explore the function and mechanism of DUSP14 in asthma-related airway inflammation. In an ovalbumin (OVA) asthma mouse model, DUSP14 was found to be significantly diminished. DUSP14 overexpression relieved airway inflammation and attenuated airway mucus production. In vitro , overexpression of DUSP14 attenuated IL-13-induced cellular inflammation and mucus hypersecretion in bronchial epithelial cells (BEAS-2B). Afterwards, we used the co-immunoprecipitation assay to confirm that DUSP14 interacted with TAK1. DUSP14 overexpression restrained the activation of TAK1 and NF-κB signaling pathway in vitro and in vivo . Taken together, our findings clearly showed that DUSP14 could alleviate airway inflammation by inhibiting TAK1 activity and NF-κB signaling pathway, positioning the DUSP14-TAK1-NF-κB regulatory axis as a potential therapeutic target for allergic asthma.
研究领域:
免疫学
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呼吸病学
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分子生物学
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