INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jing-Mei Lu,Xiang Xu,Fumie Aosai,Ming-Yue Zhang,Lu-Lu Zhou,Lian-Xun Piao
Toxoplasma gondii ( T. gondii )-derived heat shock protein 70 ( T.g. HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g. HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A 2 (cPLA 2 ) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii ) on allergic liver injury using T.g. HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii -induced allergic acute liver injury. The results showed that ARC suppressed the T.g. HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g. HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA 2 , PAF, and interferon-γ. This result suggested that ARC ameliorates T.g. HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g. HSP70-induced allergic liver injury.
研究领域:
免疫学
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药理学
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寄生虫学
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肝病学
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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
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Dan Su,Aitong Lei,Chunchao Nie,Yi Chen
The potential mechanism for the protective effect of Ganoderma atrum ( G. atrum ) polysaccharide (PSG-1) on acrylamide (AA) induced intestinal damage in mice was explored. Results showed that PSG-1 pretreatment prevented AA-induced injury by decreasing intestinal permeability and serum D-lactate acid (D-Lac) levels and increasing the number of small intestinal goblet cells and IgA secreting cells. In addition, PSG-1 pretreatment effectively reduced malondialdehyde (MDA) level and raised superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in the intestine. Furthermore, PSG-1 administration decreased the levels of pro-inflammatory factors including IL-1β, TNF-α, and IL-6, while the anti-inflammatory factor IL-10 was elevated. Meanwhile, PSG-1 could increase the performance of tight junction (TJ) proteins such as Occludin , Claudin-1 and ZO-1. Moreover, according to the isobaric tag for relative and absolute quantitation (iTRAQ) and Western blot results, PSG-1 could reduce AA-induced intestinal injury through TLR4/MyD88/NF-κB signaling pathway. Overall, the present study suggested that PSG-1 protected intestinal permeability and barrier function in mice via reducing inflammation and oxidative stress , and effectively prevented AA-induced intestinal injury in mice.
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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毒理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hui-Hui Guo,Yan-Xing Han,Xiao-Juan Rong,Zhen Shen,Hao-Ran Shen,Ling-Fei Kong,Yun-Dan Guo,Ji-Zhou Li,Bo Xu,Tian-Le Gao,Lu-Lu Wang,Cai Tie,Jian-Dong Jiang
Background Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. Conclusions The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
研究领域:
药理学
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免疫学
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微生物学
·
呼吸医学
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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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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Chenming Zou,Ruihua Cai,Yunbing Li,Yu Xue,Guoguang Zhang,Gulimiran Alitongbieke,Yutian Pan,Sanguo Zhang
Recently, increasing evidence has shown the association between liver abnormal inflammation and cognition impairment, yet their age-related pathogenesis remains obscure. Here, our study provides a potential mechanistic link between liver macrophage excessive activation and neuroinflammation in aging progression. In aged and LPS-injected C57BL/6J mice, systemic administration of β-chitosan ameliorates hepatic macrophage-driven inflammation and reduces peripheral accumulations of TNF-α and IL-1β. Downregulation of circulatory pro-inflammatory cytokines then decreases vascular VCAM1 expression and neuroinflammation in the hippocampus, leading to cognitive improvement in aged/LPS-stimulated mice. Interestingly, β-chitosan treatment also exhibits the beneficial effects on the behavioral recovery of aged/LPS-stimulated zebrafish and Caenorhabditis elegans . In our cell culture and molecular docking experiments, we found that β-chitosan prefers shielding the MD-2 pocket, thus blocking the activation of TLR4-MD-2 complex to suppress NF-κB signaling pathway activation. Together, our findings highlight the extensive therapeutic potential of β-chitosan in reversing aged-related/LPS-induced cognitive impairment via the liver-brain axis.
研究领域:
免疫学
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神经科学
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老年学
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药理学
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产品关联
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
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药理学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR IMMUNOLOGY
·
2024
·
IF 3.2
Nini Jia,Yun Meng,Jing Li,Mengyao Cui,Yaqing Li,Dayuan Jiang,Xiaoqin Chu
Objective To study the therapeutic effect and mechanism of Shaoyao Gancao Decoction (SGD) on ulcerative colitis (UC) mice based on the perspective of intestinal barrier, and this study provides a new consultation for the clinical application of SGD. Methods The chemical composition of SGD was characterized by HPLC. The UC mouse model was constructed by 3 % dextran sodium sulfate (DSS), which were randomly divided into the model group (DSS), the positive drug group (5-ASA), the Shaoyao group (SYD), Gancao group (GCD), and the Shaoyao Gancao Decoction group (SGD) at low, medium, and high dosages, respectively. The effects of each drug treatment group on UC were evaluated by the rate of body weight loss, disease activity index (DAI), colon length, spleen index, histopathological evaluations, and the levels of serum inflammatory factors (IL-1β, IL-6, IL-10, IL-21, and TNF-α). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining, ELISA was used to detect the content of LPS in serum, and Western blot was used to detect the changes in the expression of tight junction proteins ZO-1, occludin, and the pathway proteins TLR4 and NF-κBp65 in the colonic tissues, to explore the protective effect of SGD on the intestinal barrier of UC mice. The vivo absorption process of the main active ingredients in the SG, SY and GC groups was determined by LC-MS. Results The contents of albiflorin, paeoniflorin, liquiritin apioside, liquiritin and glycyrrhetinic acid were 6.1227 mg/g, 20.8993 mg/g, 4.0054 mg/g, 3.6140 mg/g and 8.2515 mg/g, respectively. Compared with DSS group, SGD reduced weight loss(P<0.01) and DAI scores(P<0.05), prevented colon shortening(P<0.01), and ameliorated histopathological damage of the colon in UC mice(P<0.01). SGD also protected the intestinal barrier to alleviate UC by significantly reducing serum LPS and inflammatory factor levels, altering the number of goblet cells, promoting tight junction proteins (ZO-1 and occludin) and decreasing the expression of TLR4 and NF-κB in colonic tissues. Pharmacokinetic results showed that there was no significant difference in C max , AUC 0-t (μg/L . h) and T max of albiflorin and paeoniflorin between the SY and SG groups, the T max was within 1 h; the AUC 0-t (μg/L . h) of liquiritin and glycyrrhizic acid were about 1.6 and 1.9 times higher in the SG group compared to the GC group, respectively. The C max , T max and AUC 0-t (μg/L . h) of glycyrrhizinic acid were significantly reduced to 0.73, 0.68 and 0.68 times of that of the GC group. Conclusion SGD may have a therapeutic effect on DSS-induced UC mice by repairing the damaged intestinal barrier through the TLR4/NF-κB pathway. The combination of Shaoyao and Gancao increased the absorption of liquiritin and glycyrrhizic acid in vivo. The combination of Shaoyao and Gancao could promote the absorption of Gancao, and that the pairing of the two herbs could have a synergistic effect.
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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中医
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 13
·期 3
·1393-1407
·
IF 5.396
Liuming Xie,Zhibing Huang,Hui Meng,Zhibing Fan,Xiaoyi Shi,Jianhua Xie
Manipulating the structures, physicochemical properties, and monosaccharide compositions of exopolysaccharides (EPS) isolated from microorganisms has been reported to enhance their biological activities. Hence, the aim of this work was to examine the effects of genistein addition during fermentation on the amount, physicochemical properties, and immunomodulatory activity of EPS secreted by M. purpureus. Results showed that genistein addition significantly increased M. purpureus biomass and EPS yield to 2.42 g L−1 and 6.08 g L−1, respectively, and affected the physicochemical properties and structures of EPS. Furthermore, EPS produced by genistein-treated M. purpureus (G-EMP) improved the immunomodulatory activity of RAW264.7 macrophages by increasing the secretion of nitric oxide and cytokines. Moreover, phospho-Jun N-terminal kinase (p-JNK), phospho-extracellular regulated protein kinase (p-ERK), phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) phospho-p65 (p65) proteins were remarkably upregulated by G-EMP stimulation, blocking Toll-like receptor 4 (TLR4) that dramatically reduced the pinocytic and phagocytic capacities. Overall, these findings provide potential rationales for the application of genistein in improving the EPS yield of M. purpureus.
研究领域:
微生物学
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免疫学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
Microbial Biotechnology
·
2023
·
IF 5.7
Xinyue Ye,Jian Wang,Pengfei Xu,Xiaoqian Yang,Qixue Shi,Genyan Liu,Zhaoshi Bai,Changlin Zhou,Lingman Ma
Polymyxin resistance is conferred by MCR-1 (mobile colistin resistance 1)-induced lipopolysaccharide (LPS) modification of G − bacteria. However, the peptide MSI-1 exerts potent antimicrobial activity against mcr-1 -carrying bacteria . To further investigate the potential role of MCR-1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI-1, we first explored outer membrane vesicle (OMV) alterations of mcr-1 -carrying bacteria in the presence and absence of sub-MIC MSI-1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR-1 negatively affected OMV formation and protein cargo by E. coli . In addition, MCR-1 diminished LPS-stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli . Similarly, TLR4-mediated NF-κB activation was markedly alleviated once LPS was modified by MCR-1. However, peptide MSI-1 at the sub-MIC level inhibited the expression of MCR-1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR-1 during both infection and OMV stimulation, which can be exploited for anti-infective therapy.
研究领域:
微生物学
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免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）