INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Honglei Zhang,Yun Lu,Yuanlei Zhang,Jiayu Dong,Su Jiang,Yunping Tang
Objective This study explores the therapeutic effects and mechanisms of DHA-enriched phosphatidylserine (DHA-PS) on liver injury induced by cyclophosphamide (CTX) in mice, focusing on the gut-liver axis. Methods A mouse model was established by administering CTX (80 mg/kg) intraperitoneally for 5 days. DHA-PS (50 or 100 mg/kg) was administered for the next 7 days to assess its reparative impact on liver damage. Results The findings revealed significant improvements in liver biochemical indices, inflammatory markers, and oxidative stress levels in the mice treated with DHA-PS. Through non-targeted metabolomics analysis, DHA-PS mitigated CTX-induced metabolic disruptions by modulating lipid, amino acid, and pyrimidine metabolism. Immunofluorescence analysis further confirmed that DHA-PS reduced the expression of liver-associated inflammatory proteins by inhibiting the TLR4/NF-κB pathway. Additionally, DHA-PS restored the intestinal barrier, evidenced by adjustments in the levels of intestinal lipopolysaccharide (LPS), secretory immunoglobulin A (sIgA), and tight junction proteins (Claudin-1, Occludin, and ZO-1). It also improved gut microbiota balance by enhancing microbial diversity, increasing beneficial bacteria, and altering community structures. Conclusion These results suggest that DHA-PS could be a potential therapeutic agent or functional food for CTX-induced liver injury through its regulation of the gut-liver axis.
研究领域:
药理学
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肝病学
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胃肠病学
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免疫学
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代谢组学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Kang Dong,Xin Wang,Ze-jia Zhou,Xin-ru Zheng,Zhuang-peng Chang,Rui Zhao,Jun-jin Liu,Rui-gang Hou,Xiao Zhang,Yun-yun Shao
Introduction Ulcerative colitis (UC) is a chronic intestinal disease characterized by spleen-lung qi deficiency and dampness-pathogenic obstruction. Although there are various treatment options available, patients frequently encounter significant drug-related side effects. Previous studies have shown the potential of Codonopsis Radix polysaccharides A (CPA) in treating UC, but their limited bioavailability has restricted their clinical use. Therefore, the objective of this study was to develop a novel formulation that can address the aforementioned limitations and assess its potential advantages.Methods and Results We synthesized a negatively charged amphipathic prodrug called CPA-SA-DHA (CSD), which consists of CPA as the hydrophilic component, and succinic anhydride and docosahexaenoic acid as the hydrophobic segments. The CSD nanoparticles obtained had a particle size of 180.0 ± 3.2 nm, a negative zeta potential of −29.8 ± 5.3 mV, and a uniform shape with a PDI index of 0.230 ± 0.003. The interaction between positive and negative charges significantly increased the retention time of CSD nanoparticles in the colonic microenvironment. Furthermore, CSD nanoparticles demonstrated enhanced bioavailability in UC mice compared to CPA. Additionally, we observed that CSD nanoparticles exhibited therapeutic effects on DSS-induced UC mice by regulating the diversity and abundance of gut microbiota. This effect may be mediated by the inhibition of pro-inflammatory signaling pathways TLR4/NF-κB.Conclusion These findings confirm the potential of CSD nanoparticles as a promising treatment option for UC.
研究领域:
药学
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胃肠病学
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纳米技术
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免疫学
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DOI
PubMed
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2020
·Vol. 98
·期 6
·
IF 1.946
Di Wang,Meilan Zhou,Yan Wang,Shiren Sun
Xerostomia is a self-conscious symptom. High-mobility group box 1 (HMGB1) promotes pro-inflammatory effects in many diseases. This study aimed to clarify the role of HMGB1 in Sjögren syndrome (SS)-triggered xerostomia. Nonobese diabetic (NOD)/Ltj mice were used to establish an SS-triggered xerostomia model. The results showed that saliva production was decreased and anti-Sjögren syndrome B (anti-SSB) level was increased in SS. PCR, Western blot, and immunohistochemistry experiments indicated that the HMGB1 and aquaporin 5 (AQP5) levels were enhanced and diminished in SS compared with those in the control, respectively. While the mice were treated with anti-HMGB1, xerostomia was reversed due to the elevated saliva production and reduced anti-SSB level. In addition, it was found that the inhibition of HMGB1 restrained the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) axis activation. The TLR4 and p-IκB levels were alleviated, while the IκBα and NF-κB p65 levels were augmented. The NF-κB p65 binding activity was attenuated via the electrophoretic mobility shift assay (EMSA) after anti-HMGB1 treatment. Moreover, the repression of HMGB1 facilitated the expression of AQP5. These findings demonstrate that suppression of HMGB1 ameliorates SS-triggered xerostomia via suppressing the HMGB1/TLR4/NF-κB signaling pathway and upregulating AQP5 expression.
研究领域:
免疫学
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分子生物学
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疾病模型
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2026
·
IF 3.6
Renjun Gao,Yu Cai,Xue Jiang,Xue Li,Jingrui Li,Yu Kang
Background Safflower yellow injection (SYI) has demonstrated cardioprotective effects on myocardial ischemia/reperfusion (MI/R) injury. This study aimed to explore its mechanistic basis. Methods H9c2 cells were pre-treated with 80 μg/mL SYI for 24 h before exposure to oxygen-glucose deprivation/reoxygenation (OGD/R). Protein levels related to endoplasmic reticulum (ER) stress and apoptosis were detected by western blot (WB). IL‑6 and TNF‑α protein and mRNA levels were determined by ELISA and qPCR. CCK-8 test and flow cytometry were used to measure cell viability and apoptosis, respectively. Moreover, the expression of proteins implicated in HMGB1/TLR4/NF-κB pathway was measured by WB assay. Finally, rescue validation was performed using recombinant HMGB1 (rHMGB1). Results SYI treatment alleviated OGD/R-induced ER stress and reduced IL-6 and TNF-α levels in H9c2 cells. These changes were accompanied by increased cell viability and reduced OGD/R‑induced apoptosis. Mechanistically, SYI significantly restrained activation of the HMGB1/TLR4/NF-κB signaling cascade in H9c2 cells triggered by OGD/R. Further rescue experiments with recombinant HMGB1 (rHMGB1) reversed the protective effects of SYI against OGD/R damage. Conclusion These findings indicate that the HMGB1/TLR4/NF‑κB axis mediates the protective effects of SYI against myocardial OGD/R injury, potentially through modulating ER stress and inflammatory responses. This study provides a mechanistic basis for the cardioprotective action of SYI in vitro and informs future investigations into its therapeutic potential. However, these results are derived from cell-based experiments alone, and further validation in animal models is needed to confirm the in vivo relevance of this mechanism.
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DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 2
·129
·
IF 4.5
Liu Shanshan,Yan Jing,Dong Jian
This study investigates the early synergistic effects of curcumin and licorice through vertical cooperation, which can simultaneously target both the upstream and downstream components of neuroinflammation. It evaluates their neuroprotective effects and potential mechanisms in a d -galactose/sodium nitrite-induced Alzheimer’s disease mouse model.Eighty C57BL/6 mice were divided into eight groups ( n = 10): wild-type (WT), AD model, curcumin monotherapy (AD + CL, 100 mg/kg), G. glabra monotherapy (AD + GG, 100 mg/kg), low-dose combination (AD + COM-L, 50 + 50 mg/kg), high-dose combination (AD + COM-H, 100 + 100 mg/kg), donepezil (3 mg/kg), and SN50 (NF-κB inhibitor, 400 µg/kg). Cognitive function was assessed via Morris Water Maze in WT, AD, AD + CL, AD + GG, and AD + COM-H groups, while all groups underwent molecular analyzes. The high-dose combination most effectively restored spatial memory, reducing escape latency by ~ 43% versus monotherapies. Molecularly, it synergistically reduced tau-related proteins (MAPT, GSK-3β) and suppressed the TLR4/MyD88/NF-κB axis, lowering inflammatory mediators (IL-6, TNF-α, CXCL1, PTGS2). IL-6 was further reduced by 28.6% and 40.0% compared to curcumin and G. glabra alone, respectively. The combination also enhanced antioxidant defense (increased SOD) and anti-apoptotic capacity (upregulated BCL-2) while reducing oxidative lipid damage (lower MDA). Network pharmacology identified 40 shared AD targets, with enrichment in NF-κB and IL-17 pathways, validated experimentally. In conclusion, curcumin and G. glabra exert synergistic neuroprotection by concurrently inhibiting the TLR4/NF-κB pathway and modulating IL-17 signaling, with G. glabra potentially targeting the TLR4/HMGB1 axis and curcumin directly inhibiting NF-κB activation, forming a complementary mechanistic interplay. This multi-target action disrupts the interplay between neuroinflammation and tau pathology, underscoring the combination’s therapeutic potential for AD intervention.
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DOI
PubMed
高影响因子
Cell Death Discovery
·
2025
·Vol. 11
·期 1
·1-15
·
IF 7
Zheng Xiao-Bo,Wang Xue,Gao Sheng-Qing,Gao Chao-Chao,Li Tao,Han Yan-Ling,Zhao Ran,Sun Yan,Miao Shu-Hao,Qiu Jia-Yin,Jin Wang-Xuan,Zhou Meng-Liang
Brain endothelial cell (bEC) dysfunction is the main factor of blood-brain barrier (BBB) breakdown, which triggers a vicious cycle of aggravating traumatic brain injury (TBI) pathogenesis. Previous studies have revealed that neutrophil extracellular traps (NETs) released by neutrophils can lead to BBB disruption, but there is a lack of research on the underlying mechanisms after TBI. Here, excessive NETs were found in both contused brain tissue and circulation following TBI. We found that NETs could activate the TLR4/NF-κB pathway to induce bEC pyroptosis, which led to BBB disruption after TBI. During this process, ninjurin-1 (NINJ1) was activated in pyroptotic bECs, and it mediated the release of high mobility group box 1 protein (HMGB1) via plasma membrane rupture (PMR) to promote NET formation. NINJ1-mediated release of HMGB1 aggravated NET accumulation by forming a vicious circle following TBI. Knockdown of NINJ1 rescued NET formation, attenuated BBB leakage, and improved neurological outcomes after TBI. NINJ1 may represent a promising target for alleviating NET-induced BBB destruction and other related injuries after TBI.
研究领域:
神经科学
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免疫学
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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
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yang Zheng,Jiahui Wang,Jiaru Wang,Ruizhu Jiang,Tiejian Zhao
Objective Liver fibrosis is a reversible pathological process, and its prevention and treatment hold great significance for patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and serum metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results clarified the relationship between the gut microbiota and metabolites in the process of liver fibrosis. Materials and methods In this study, we randomly divided mice into a control group, a model group, and a curcumol treatment group to analyze the pathological changes in the liver tissue as well as the activities of the toll-like receptor 4 (TLR4)/nuclear factory kappa B (NF-κB) signaling pathway and inflammatory factors, such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-8. The gut microbiota were analyzed by 16 S rRNA sequencing, and serum metabolites were examined by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Results Molecular biological testing found that curcumol could significantly improve the pathological changes of the liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s antihepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2. Conclusions When liver fibrosis occurs, the intestinal flora and metabolic network are altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby reducing liver inflammation.
研究领域:
药理学
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肝病学
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微生物学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Shuhan Li,Zhanpeng Zhu,Tian Lan,Yuhan Wu,Ye Li,Changmin Wang,Wencheng Jian,Shu Yan Yu
Levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, has been reported to have anti-depressive effects. However, the detailed mechanisms underlying these effects are still unclear. This study aimed to investigate the antidepressant mechanisms of levomilnacipran to discover new perspectives on the treatment of depression in male rats. Intraperitoneal injection of lipopolysaccharide (LPS) was used to induce depressive behaviors in rats. Activation of microglia and apoptosis of neurons verified by immunofluorescence. Inflammatory related proteins and neurotrophic related proteins were verified by immunoblotting. The mRNA expression of apoptosis markers was verified by real-time quantitative PCR. Finally, electron microscopy analysis was used to observe the ultrastructural pathology of neuron. Here, we found that the anti-depression and anti-anxiety effects of levomilnacipran in the LPS-induced rat model of depression was resulted from the suppression of neuroinflammation and neuronal apoptosis within prefrontal cortex of rats. Furthermore, we found that levomilnacipran could decrease the number of microglia and suppress its activation in prefrontal cortex of rats. This effect may be mediated by suppressing the TLR4/NF-κB and Ras/p38 signaling pathways. In addition, levomilnacipran plays a neuroprotective role by increasing the expression of neurotrophic factors. Taken together, these results suggest that levomilnacipran exerts antidepressant effects by attenuating neuroinflammation to inhibit the damage in central nervous system and plays a neuroprotective role to improve depressive behaviors. These findings suggest that suppression of neuroinflammation in prefrontal cortex could ameliorate depressive behavioral disorder of rats induced by LPS, which provided a new perspective for the treatment of depression.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 30
·期 4
·1-10
·
IF 3.4
Ying Chen,Yu Li,Xiaojuan Li,Qingqing Fang,Feng Li,Shiyao Chen,Weichang Chen
Indole‑3‑propionic acid (IPA), a product of Clostridium sporogenes metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)‑induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit‑8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPS‑induced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens‑1, claudin‑1 and occludin). Furthermore, IPA inhibited the release of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α) in a dose‑dependent manner and this was achieved via regulation of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor 88/NF‑κB and TLR4/TRIF/NF‑κB pathways. In conclusion, IPA may alleviate LPS‑induced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPS‑induced intestinal epithelial cell injury and intestinal barrier dysfunction.
研究领域:
胃肠病学
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免疫学
·
细胞生物学
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药理学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xinxin Hou,Zhaozhou Zhang,Wanqing Chen,Jinming Li,Xiangxiang Zhu,Mingjie Li,Xiaoqi Guan,Haidong Guo,Yanlei Ma,Ling Zhao
Altered gut microbiota has evidenced to be associated with colitis and colonic tumorigenesis, however bacteria-driven mechanism underlying inflammation-related colon pathologies remains undetermined. This study identifies a previously overlooked genus, Megasphaera , is highly abundant in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) cohorts. A Megasphaera species, M. elsdenii reshapes colonic immunity by triggering dendritic cell (DC)-mediated Th1 and Th17 inflammation. Mechanistically, M. elsdenii and its lipopolysaccharide triggers DC activation via TLR4/NF-κB/IRF4 pathway. Accordingly, in Tlr4 −/− mice, M. elsdenii colonization cannot expand colonic infiltration of DCs and fails to induce Th1 and Th17 responses in. In a Shanghai CRC cohort with a 100% detective rate for Megasphaera , the species of Megasphaera significantly dominated in early onset CRC patients (<50 years old) rather than late-onset CRC (≥50 years old). M. elsdenii and M. elsdenii -enriched microbiota exacerbate colonic inflammation and tumorigenesis in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine colitis-associated cancer model. Taken together, this study uncovers a pathogenic role of Megasphaera in developing colonic tumorigenesis via activating DC-mediated inflammation.
研究领域:
微生物学
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免疫学
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肿瘤学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Jing Tian,Feng Xiao,Yezhu Xu,Yuen Chen,Chenli He,Su Jiang,Yunping Tang
α-Monoglucosyl rutin (α-GR) is a structurally optimized rutin derivative, and its higher water solubility and bioavailability may help it exert better pharmacological effects in vivo . The present study examined the protective effects and potential mechanisms of α-GR on cyclophosphamide (CTX)-induced colonic injury in mice. The findings showed that α-GR significantly reduced serum levels of lipopolysaccharide (LPS) and diamine oxidase (DAO), effectively alleviating the histopathological damage in colon tissues caused by CTX exposure. Additionally, α-GR maintained the integrity of intestinal epithelial cells by promoting the secretion of secretory immunoglobulin A (sIgA) and upregulating the expression of tight junction proteins (Claudin-1 and ZO-1), while also reducing the levels of colonic pro-inflammatory factors and oxidative stress. In terms of gut microbiota, 16S rRNA gene sequencing and metabolomic analyses revealed that α-GR could effectively reverse the gut metabolic disorders and microbiota structural changes induced by CTX, promoted the growth of beneficial bacteria like norank_f_Muribaculaceae , Bacteroides, and Alloprevotella , and reduced the relative abundance of pathogenic bacteria ( Desulfovibrio ), while also revealing the complex correlation between them. In terms of mechanism research, α-GR further attenuated intestinal damage by regulating the TLR4/NF-κB and Nrf2/HO-1 pathways. This provides new ideas for the development of functional dietary supplements to treat CTX-associated intestinal toxicity.
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Jiahao Liao,Jianyu Huang,Xiaoyi Chi,Xiaoqiong Li,Jian Kuang,Jianqiang Li,Xiangyu Bian,Jinzhu Pang,Jinjun Li,Weiwei Wang
In this study, D-mannose-modified nanoliposomes (MLipo@OVA) were developed to facilitate the targeted delivery of ovalbumin (OVA) to macrophages. The subsequent anti-inflammatory, antioxidant, and macrophage-polarizing effects of OVA were investigated. The nanoliposomes were designed with DSPE-PEG and DPPC to enhance the bioavailability and stability of OVA. In vitro analysis showed that MLipo@OVA significantly increased macrophage uptake, with D-mannose further enhancing this effect. MLipo@OVA reduced pro-inflammatory cytokines (TNF-α, IL-1β) and increased anti-inflammatory IL-10 levels in LPS-induced macrophages, primarily via the inhibition of the TLR4/NF-κB pathway. Furthermore, ROS levels were decreased, SOD and GSH activity was enhanced, the Nrf2/HO-1 pathway was activated, and the compound exhibited strong antioxidant activity. MLipo@OVA also promoted M2 macrophage polarization by upregulating CD206 and Arg-1 and downregulating iNOS. Overall, these results indicate that MLipo@OVA could be used as a nanomedicine to facilitate targeted anti-inflammatory and antioxidant therapies.
研究领域:
药学
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免疫学
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纳米技术
·
药理学
✓ 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）