INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zong-hui Xu,Man Li,Lin Liu,Shu-jing Wu,Ruo-an Wei,Mpofu Uphakeme Inobubele Sitholumusa,Xiao-ping Zhao,Jun-qiu Liu,Guo-yin Kai
Astragaloside IV (AS-IV), derived from Astragalus membranaceus , exhibits significant anti-inflammatory properties in a variety of diseases. However, the specific anti-inflammatory mechanism of AS-IV depends on the different organs and doses. Its protective effect is still unknown in acute lung injury (ALI). This study aims to investigate the potential anti-inflammatory mechanism of AS-IV in ALI. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were utilized to form pyroptosis models in MH-S and RAW264.7 cells. Mouse model of ALI was induced by intranasal LPS administration. In addition, the anti-pyroptosis effect of AS-IV was evaluated by using the C5aR1 agonists BM-213, the C5aR1 overexpression plasmids and C5aR1 siRNA. AS-IV significantly reduced pulmonary edema, improved histopathological injury, and decreased inflammatory factors. Meanwhile, AS-IV reduced ROS level and the amount of NLRP3 and GSDMD-N in vitro and in vivo . Inhibiting C5aR1 can effectively and significantly alleviate the pyroptosis of alveolar macrophages. Further studies found that BM-213 and C5aR1 overexpression plasmids partially reversed the anti-pyroptosis effect of AS-IV. The anti-pyroptosis effect of AS-IV was significantly inhibited when C5aR1 was knocked down. Our study demonstrate that AS-IV has anti-inflammatory protective effects on LPS-induced ALI, indicating that AS-IV may be a potential therapeutic agent for the treatment of ALI. This effect may be achieved by reducing the content of C5a, lowering the expression of C5aR1, and inhibiting cell pyroptosis.
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2025
·Vol. 40
·期 8
·324
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IF 3.5
Tian Lei,Su Pan,Feng Gang,Peng Shuaijun,Liu Liming,Yan Xiangli,Liu Xianghua,Li Yucheng,Bai Ming,Wang Baoying,Xu Erping
Modified Xiaoyao San (MXYS) is a well-established clinical prescription for the treatment of depression in China. While MXYS shows considerable promise for the development of new antidepressants, its pharmacological mechanisms remain poorly understood. This study aims to investigate the antidepressant potential and underlying mechanisms of MXYS in lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Behavioral assessments (sucrose preference test, tail suspension test, open field test) demonstrated that MXYS significantly ameliorated LPS-induced anhedonia and behavioral despair. Histopathological and molecular analyses revealed that MXYS mitigated LPS-induced neuronal damage in the prefrontal cortex (PFC), restored dendritic spine density, and rebalanced neuroinflammatory cytokines by reducing the pro-inflammatory IL-1β and elevating the anti-inflammatory IL-10. Moreover, MXYS promoted microglial polarization toward the anti-inflammatory M2 phenotype (CD206⁺) while suppressing the pro-inflammatory M1 phenotype (CD68⁺). Mechanistically, MXYS inhibited NLRP3 inflammasome activation and pyroptosis through the upregulation of the E3 ubiquitin ligase TRIM31, which facilitated NLRP3 degradation. Transmission electron microscopy confirmed that MXYS inhibited LPS-induced microglial pyroptosis, as evidenced by reduced Gasdermin D (GSDMD) expression and preserved cellular ultrastructure. In vitro validation using LPS-stimulated BV2 microglia further corroborated the MXYS-mediated suppression of NLRP3 inflammasome activity, pyroptosis, and inflammatory cytokine dysregulation, alongside enhanced TRIM31 expression. Collectively, these findings demonstrate that MXYS exerts antidepressant effects by modulating neuroinflammation through TRIM31-dependent NLRP3 ubiquitination, microglial phenotype switching, and the inhibition of pyroptosis, providing novel insights into its therapeutic potential for the treatment of depression. Graphical
研究领域:
药理学
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神经科学
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免疫学
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中医中药
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分子生物学
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DOI
PubMed
高影响因子
Neuropsychiatric Disease and Treatment
·
2022
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IF 2.989
Kun Zhang,Ran Liu,Yuan Gao,Wen Ma,Weidong Shen
Background Neuroinflammation is an important pathological mechanism of depression that leads to an increase in indoleamine-2,3-dioxygenase (IDO) activity and NMDAR activation. This study aimed to observe the effects of electroacupuncture on depression-like behaviour in lipopolysaccharide (LPS)-treated rats and the underlying mechanism.Methods Wistar rats were intraperitoneally administered LPS (0.5 mg/kg) for 7 consecutive days to establish a depression model. Electroacupuncture treatment was administered 1 hour after daily LPS injection. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to evaluate the depressive-like behaviours. IL-1β, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA); Trp, 5-hydroxytryptamine (5-HT), kynurenine (Kyn) and quinolinic acid (Quin) were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry; and N-methyl-D-aspartate receptor (NMDAR) protein and mRNA were assessed by Western blot and real-time qPCR.Results The results showed that electroacupuncture treatment successfully corrected LPS-induced depressive-like behaviour, reduced the inflammatory factor (IL-1β, IL-6 and TNF-α) levels in the blood and hippocampus, prevented IDO over-activation and recovered NR2B expression after challenge by LPS.Conclusion Electroacupuncture treatment provided protection against LPS-induced depressive-like behaviour, and the associated mechanisms may be related to inhibiting the inflammatory response, regulating the IDO-mediated tryptophan-degrading pathway, and inhibiting NR2B activation.
研究领域:
神经科学
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药理学
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免疫学
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行为科学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shanbo Ma,Rui Zhang,Long Li,Jin Wang,Meiling Zheng,Xiaodi Guo,Shan Miao,Wei Quan,Wenjuan Liu,Xiaopeng Shi
The current study isolated a homogeneous polysaccharide (AP) with a molecular weight of 7.9 kDa from the pomace of Fuji apples. AP was found to consists of rhamnose, galactose, arabinose, glucose, and galacturonic acid in a ratio of 4.3:5.2:2.6:1.0:11.9. Ten sugar residues in AP, including T-Ara f , 1,5-Ara f , 1,2-Rha p , 1,3-Rha p , T-Gal p , 1,3,5-Ara f, 1,4-Gal p , 1,4-Gal p A, 1,6-Glc p , and 1,3,6-Glc p were identified using methylation and GC–MS. Combined with 1D and 2D NMR, it was further revealed that AP possesses a backbone of α-Gal p- (1 → [3)-α-Rha p -(1 → 2)-α-Rha p -(1] 2 → [4)-α-Gal p A-(1] 10 → 3,6)-β-Glc p -(1 → 6)-β-Glc p -(1 → 4)-β-Gal p -(1 → 4)-β-Gal p -(1→, with two branches: α-Ara f -(1 → 5)-α-Ara f -(1 → 5)-α-Ara f -(1 → 3,5)-α-Ara f -(1 → 6)-β-Glc p -(1→ and →3)-α-Rha p -(1 → 5)-α-Ara f -(1 → 3,6)-β-Glc p -(1→ bonded to the C-3 of β-1,3,6-Glc p . AP significantly inhibited the release of cytokines and inflammatory mediators, such as TNF-α, IL-1β, IL-6, reactive oxygen species (ROS) and nitric oxide (NO). Western blotting results indicated that AP treatment markedly downregulated iNOS and NF-κB protein expression in LPS-induced RAW264.7 cells, leading to decreased levels of phosphorylated proteins (p-NF-κB and p-ΙκΒα) and preventing the degradation of ΙκΒα. Furthermore, in LPS-induced RAW264.7 macrophages, AP inhibited the expression of TLR4 protein, which in turn inhibited the activity of the NF-κB pathway. The findings demonstrated that AP exhibits anti-inflammatory properties in vitro by targeting the TLR4/NF-κB signaling pathway, thus impeding the nuclear translocation of NF-κBp65, suppressing the expression of related pro-inflammatory factors.
研究领域:
食品科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2019
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IF 4.18
Hongjin Chen,Yali Zhang,Wenxin Zhang,Hui Liu,Chuchu Sun,Bing Zhang,Bin Bai,Di Wu,Zhongxiang Xiao,Hazel Lum,Jianmin Zhou,Ruijie Chen,Guang Liang
Background ALI/ARDS is characterized by severe hypoxemic respiratory failure attributed to inflammatory tissue injury. There are no treatment modalities able to prevent/reverse the dire pathological sequelae in these patients . Evidence links the inflammatory lung injury to uncontrolled activation of the immune signaling complex, TLR4-MD2 (Toll-like receptor-myeloid differentiation factor 2). Baicalein , a natural flavonoid , is reported to have robust anti-inflammatory properties, but its inhibition mechanism remains unclear. Hypothesis/Purpose This study investigated the protective mechanisms of baicalein on ALI/ARDS. Methods We used two experimental mouse models of LPS-induced ALI , pulmonary infection model (intratracheal LPS), and systemic infection model (intravenous LPS). Blood, BALF , lung and liver tissues were analyzed using routine methods. In vitro studies using peritoneal mouse macrophages or recombinant proteins were designed to elucidate inhibition mechanisms of baicalein. Results Our critical new findings revealed that Baicalein was an MD2 inhibitor, directly bound to MD2, effectively suppressing TLR4-MD2 activation and the subsequent MAPK and NF-κB signaling. The inhibited MD2 prevented development of inflammatory tissue injury and improved survival. The importance of MD2 in the inflammatory injury in ALI was corroborated by data obtained from MD2 −/− mice, which did not develop the characteristic LPS-induced lung tissue damage. Thus, the findings indicated that MD2 was critical for development of ALI, functioning as an early upstream signal driving the progression of inflammatory injury. Conclusion Baicalein, as a direct and selective MD2 inhibitor, inhibited the early upstream TLR4-MD2 signaling and is a promising therapeutic agent for the treatment of ALI/ARDS.
研究领域:
免疫学
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药理学
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肺科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2019
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IF 3.559
Haihua Zhang,Haijun Gu,Qinghui Jia,Yanqing Zhao,Hongqiang Li,Shurui Shen,Xin Liu,Guisheng Wang,Qiumei Shi
Inflammatory bowel disease (IBD) is a chronic inflammatory condition with high incidence. Syringin exhibits multiple pharmacological properties, including anti-inflammatory effects. However, the effect of syringin on inflammation of IBD is still unclear. Here, the dextran sulfate sodium (DSS)-induced colitis model was established in vivo . Rat intestinal epithelium IEC6 cells were treated with lipopolysaccharide (LPS) in vitro . Syringin inhibited DSS or LPS-induced overproduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and proinflammatory substances (iNOS, COX-2). Moreover, syringin inactivated the proinflammatory NF-κB p65 pathway by decreasing IκBα phosphorylation at Ser 32. The activation of antioxidant Nrf2 signaling pathway was promoted by syringin. Additionally, LPS-induced inflammation in IEC6 cells was also suppressed by NF-κB inhibitor PDTC and Nrf2 activator RTA408. The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2015
·Vol. 52
·期 2
·228-234
·
IF 1.145
Gao Aichao,Wang Xichao,Yu Haiyan,Li Na,Hou Yubo,Yu Weixian
Porphyromonas gingivali s ( Pg ) as the major pathogenic bacterium of chronic periodontitis can cause alveolar bone resorption. Lipopolysaccharide (LPS) is its main virulence factor. The Eph family plays an important role in maintaining bone homeostasis. In this study, the effects of P. gingivalis lipopolysaccharide ( Pg -LPS) on the expression of EphA2 in osteoblasts and osteoclasts were investigated. MC3T3-E1 cells and RAW264.7 cells were separately cultured in osteoblast-conditioned medium and osteoclast-conditioned medium to induce their differentiation into osteoblasts and osteoclasts, respectively. MC3T3-E1 cells were treated with 1 μg/mL of Pg -LPS 3, 7, and 14 d later, while RAW264.7 cells were treated with 10 μg/mL of Pg -LPS 1, 3, and 5 d later. The results have shown that Pg -LPS increased the expression of EphA2 both in osteoblasts and osteoclasts, decreased the expression of osteogenic-related genes ( ALP , Sp7 ), and increased the expression of osteoclast-related genes ( MMP9 , c-fos , ACP5 , CtsK , and NFATc1 ). Tartrate-resistant acid phosphatase (TRAP) staining illustrated that Pg -LPS promoted osteoclast differentiation and decreased the activity of alkaline phosphatase. Therefore, analysis indicates that, when treated with Pg -LPS, the expression of EphA2 is upregulated while the activity of osteoblasts and osteoclasts was reduced and increased, respectively. Our data suggest that EphA2 is closely related to the formation of osteoblasts and resorption of osteoclast and is likely to play an role in bone resorption induced in chronic periodontitis. These findings may provide information on new targets for prevention and treatment of chronic periodontitis.
研究领域:
牙医学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
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2024
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IF 4.6
Weng Jiyu,Wang Ying,Tan Zekai,Yuan Yanghe,Huang Shiyuan,Li Zexi,Li Yiming,Zhang Lanyue,Du Zhiyun
Objectives Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. Methods The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. Results In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. Conclusion Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.
研究领域:
神经科学
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药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2026
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IF 3.9
Jia-fan Liang,Dong-liang Wang,Zhi-hui Zhang,Yi-xuan Li,Man Yuan,Meng-meng Ju,Ya-nan Sun,Guo-ping Zhao
Inflammatory bowel disease (IBD) is a chronic condition associated with epithelial barrier disruption, dysregulated immunity, and gut microbiota imbalance, with substantial morbidity and mortality rates. Effective treatments without side effects are limited, highlighting the need for alternatives. Edible bird's nest (EBN), a traditional health food rich in sialic acid (SA), exhibits antioxidant, immunomodulatory, and gut barrier–enhancing activities. Its effects and mechanisms against intestinal inflammation are unknown. Here we evaluated the effects of EBN on lipopolysaccharide (LPS)-induced colitis in male C57BL/6 J mice. EBN significantly attenuated LPS-induced intestinal inflammation, reduced intestinal permeability, and alleviated colonic tissue damage in a dose-dependent manner. It also increased IL-6 level and promoted M2 macrophage polarization. Furthermore, EBN altered gut microbiota composition, notably increasing the relative abundance of Blautia. Spearman correlation analysis identified strong associations between inflammatory cytokines (IL-1β, IL-6, IL-10) and beneficial taxa such as Blautia and Roseburia. These findings indicate that EBN exerts significant protective effects against LPS-induced intestinal inflammation, with SA likely acting as a key bioactive component. This work provides evidence supporting the potential of EBN as a dietary intervention for IBD treatment.
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高影响因子
Virulence
·
2026
·
IF 6.8
Hui-Hui Zhang,Yi-Dan Cao,Ying-Ying Xie,Yu-Ze Li,Xiao-Na Fan,Qiu-Yue Diao,Yu-Jiao Liang,Li-Ren He,Zi-Xing Zhong,Li-Juan Xia,Ze-Hua Cui,Xiao-Ping Liao,Xin-Lei Lian,Dong-Hao Zhao,Jian Sun,Hao Ren
Colistin holds clinical importance as a last resort therapy against infections caused by multidrug-resistant Gram-negative pathogens. In addition to well-studied plasmid-encoded mcr alleles, the adaptive mechanisms primed by host conditions are increasingly evidenced to be responsible for suboptimal efficacy of colistin in clinical practice, yet have long been neglected. Herein, we reported the identification of baicalein that potentiates colistin killing in vitro and in vivo by manipulating bacterial labile iron pool, where ferrous iron accumulates at the expense of ferric and total iron. This change in iron abundance leads to inactivation of the PmrA/B two-component system and subsequent PmrA/B-dependent lipopolysaccharide modifications, finally promoting colistin to bind and destabilize the bacterial membrane. Meanwhile, increased ferrous iron, in response to colistin-induced ROS, results in ferroptotic-like damage, which generates lethal reactive electrophilic species to deteriorate the essential cellular constituents. These data underscore an exploitable link between iron homeostasis and colistin susceptibility, as both primary and secondary actions of colistin respond to the shifts in cellular labile iron. To sum, this study offers a translationally viable regimen of baicalein-colistin combination against Gram-negative pathogen infection and reveals the cellular labile iron as a generally applicable target for developing next-generation colistin adjuvants.
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PubMed
高影响因子
Antioxidants
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2026
·Vol. 15
·期 5
·652
·
IF 8.2
Haoyang Dai,Qinqin Zhang,Pei Chen,Suiqing Chen
The pathogenesis of acute liver injury (ALI) involves the loss of hepatic detoxification function, massive death of liver parenchymal cells within a short period, and excessive inflammatory responses. Studies have shown that Esculetin (Esc) possesses potent anti-inflammatory, antioxidant, and anti-tumor properties. In this study, we investigate whether Esc has a protective effect against ALI in mice and its potential mechanism. Esculetin markedly decreased ROS, MitoSOX, and apoptosis levels in AML12 cells and restored MMP. H&E staining demonstrated that Esc alleviated hepatic histopathological injury, and its intervention reduced serum ALT and AST levels. Moreover, Esc diminished ROS and apoptosis levels in the liver. Hepatic proteomic profiling identified the AMPK signaling pathway. Esc reduced the protein levels of p-AMPK/AMPK, PGC-1α, p-SIRT1/SIRT1, and BAX and upregulated the levels of Bcl-2 in liver tissue. Concomitantly, we added inhibitor Compound C (CC) to the AML12 cells to assess whether Esc acted through the AMPK pathway. The results showed that CC exacerbated the degree of liver injury, whereas Esc was able to reverse these phenomena, thus exerting an anti-liver injury effect. These findings provide mechanistic insights into the protective effects of Esc against ALI and support its potential as a therapeutic candidate for ALI.
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DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2026
·
IF 3.4
YiXi Zeng,Yanqing Ma,Shunfan Chen,Lanyue Zhang,Hui Li
We aimed to investigate the neuroprotective effect of Echinacoside (ECH) extracted from Cistanche tubulosa (Schenk) Wight in a mouse model of LPS-induced neuroinflammation and associated memory impairment, and the potential role of the microbiota-gut-brain axis (MGBA) in this process. Intraperitoneal injection of LPS in mice can induce inflammation, causing learning and memory impairment, and it can also affect the balance of the intestinal flora. The Morris water maze (MWM) experiment, immunohistochemistry, immunofluorescence chemistry, Nissl staining, and 16S rRNA gene sequencing of the mice intestinal flora were performed for the study. The results of the MWM experiment showed that mice treated with ECH were able to find the platform faster compared to the model group, with shorter distances moved than the C. tubulosa (Schenk) Wight extract (CTE) group, and they had more platform crossings. Immunofluorescence staining of brain cortex and hippocampal tissues showed that ECH could attenuate LPS-induced neuronal damage and reduce the expression levels of Ionized calcium-binding adapter molecule 1 (Iba-1) positive cells and the Tumor Necrosis Factor-alpha (TNF-α). 16S rRNA gene sequencing of mice intestinal flora revealed that ECH exerted beneficial effects by reshaping the structure of the intestinal flora. Our findings suggest that ECH may be beneficial for alleviating neuroinflammation-related cognitive impairments, providing theoretical support for a new neuro-psycho-pharmacological approach to MGBA-related diseases through restoring intestinal flora homeostasis.
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高影响因子
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