IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2025
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IF 3
Song Peng,Yang-yang Sun,Qiangqiang Chu,Hua-dong Meng,Ming-wei Hao,Yan-bei Zhang
Background Leonurine (Leo) has antioxidant and anti-inflammatory activities. In this study, we investigated the effect of Leo in a rat model of lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD).Methods Rats with COPD were administered Leo, and the pulmonary function parameters, pathological changes, and inflammatory mediators in tissues were evaluated. The expression of IκBa, p65, JAK2, STAT3, p-IκBa, p-p65, p-JAK2 and p-STAT3 was measured using western blotting.Results Leo effectively improved the clinical manifestations of COPD by decreasing the pulmonary function parameters including peak expiratory flow and expiratory flow at 50% tidal volume, and improving pathological changes. Leo reduced lung inflammation and oxidative stress by reducing CD68+ cell infiltration, regulating Treg/Th17 cell differentiation, attenuating the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-17, increasing IL-10 secretion, and regulating malondialdehyde and glutathione peroxidase levels. In vitro experiments revealed that Leo exhibits similar inhibitory effects on Th17 cell differentiation and macrophage activation. Furthermore, Leo effectively protected against LPS-induced damage to bronchial airway epithelial cells by reducing reactive oxygen species production. Mechanistic investigations revealed Leo inhibits NF-κB transcriptional activity, downregulates the levels of p-p65, p-JAK2, and p-STAT3 without affecting their total protein levels.Conclusion Our results suggest that Leo exerts therapeutic effect against COPD. Leo inhibited tissue inflammation and oxidative stress in COPD rat models via inhibition of the NF-κB and JAK2/STAT3 signaling pathways.
研究领域:
呼吸医学
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药理学
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分子生物学
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炎症研究
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信号转导
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Ruijie Wang,Ning Zhou,Jinfang Xue,Yan Li,Yang Wang,Huadong Zhu,Chuanzhu Lv
Background: In sepsis, the lung is one of the worst affected organs, often leading to acute lung injury (ALI). More and more evidence suggests that macrophages are also involved in the pathogenesis of ALI. In our previous study, we successfully synthesized Iron-capsaicin-based nanoparticles (Fe-CAP NPs) and found that it could inhibit the secretion of inflammatory cytokines to alleviate ALI. Here, we further explore the anti-inflammatory mechanism of Fe-CAP NPs.Methods: Bone marrow-derived macrophages (BMDM) and C57 mice were divided into four groups: control group, lipopolysaccharide (LPS) group, CAP + LPS group and Fe-CAP + LPS group. Western blot and Immunofluorescence were used to detect the expression of macrophage phenotypic markers CD86 and CD206 in BMDM and lung tissue. Fluorescence microbeads, Transwell and ROS kit were used to detect the phagocytosis, migration and ROS clearing capability of BMDM. Western blot was used to detect the expression of JAK2/STAT3 pathway and apoptosis proteins in BMDM. TUNEL kit and H&E staining were used to evaluate apoptosis and pathological changes in lung tissue.Results: In vitro, CD86 expression was increased in LPS, but decreased after Fe-CAP pretreatment. CD206 expression was the opposite. Fe-CAP reduced phagocytosis, migration and scavenged ROS in LPS-treated BMDM. Fe-CAP inhibited P-JAK2 and P-STAT3 expression and reduced apoptosis. In vivo, Fe-CAP improved lung histopathology and reduced apoptosis in lung tissue of LPS group. CD86 expression was increased in lung tissue of LPS group, but decreased in Fe-CAP preconditioning, and CD206 expression was reversed.Conclusion: Fe-CAP NPs could alleviate sepsis-induced ALI by regulating the polarization and function of macrophages, reducing ROS level and apoptosis.
研究领域:
免疫学
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药理学
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肺病学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Qiong Tang,Chen Xing,Ming Li,Qiang Jia,Cunxiang Bo,Zhenling Zhang
Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.
研究领域:
药理学
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呼吸医学
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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
RSC Advances
·
2017
·Vol. 7
·期 86
·54369-54378
·
IF 3.108
Mengqiao Lian,Yuchao Sun,Yuan Lin,Jin Wen,Marwan Almoiliqy,Bin Xu,Yanli Li,Ming Xu,Dapeng Chen,Zeyao Tang,Li Wang
Catalpol, an iridoid glucoside isolated from the radix of Rehmannia glutinosa Libosch, is found to have a wide variety of biological activities. Based on our pre-experiments, we proposed that catalpol pretreatment could protect against intestinal ischemia/reperfusion (I/R) injury and the JAK2/STAT3 signaling pathway might play an important role in the protection. Both in vivo intestinal I/R-injured rats and in vitro hypoxia/reoxygenation (H/R)-injured IEC-6 cells were used in the present study. The results confirmed our proposal. The in vivo results showed that catalpol (25, 50 mg kg−1) significantly attenuated rat intestinal I/R injury by decreasing pro-inflammatory cytokines, reducing oxidative stress, and restoring intestinal barrier function without affecting the corresponding controls. Catalpol pretreatment significantly increased the Bcl-2/Bax ratio, and decreased cleaved caspase3, p-JAK2, and p-STAT3 protein expression without affecting total JAK2 and STAT3 in vivo and in vitro, showing that catalpol inhibited apoptosis through selectively inhibiting p-JAK2 and p-STAT3. In vitro studies indicated that catalpol (40 μM) pretreatment significantly and selectively inhibited p-STAT3 nuclear translocation and transfection of JAK2 siRNA significantly decreased JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins in H/R-injured IEC-6 cells, suggesting that JAK2 siRNA partially simulated the effects of catalpol on apoptosis-related proteins. JAK2 siRNA + catalpol could not further decrease JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins, suggesting that inhibition of the JAK2/STAT3 signaling pathway plays a key role in catalpol-induced protective effects. Our results suggest that p-JAK2 is the key target in catalpol-induced protection against intestinal I/R injury, providing information for further translational studies.
研究领域:
药理学
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病理生理学
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分子生物学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
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IF 6.8
Yu Yang,Hongda Liu,Junling Ren,Lin Liu,Hui Sun,Li Wang,Guangli Yan,Ying Han,Xijun Wang
Ethnopharmacological relevance Danggui Buxue Decoction (DBD) is a classic traditional Chinese medicine formula that has shown significant efficacy in treating blood deficiency syndrome (BDS), though its mechanisms of action remain unclear. Aim of the study To identify the absorbed bioactive components of DBD and elucidate its molecular mechanisms in BDS by integrating metabolomics and bioinformatics. Materials and methods Using a benzene induced BDS mouse model, we analyzed serum-absorbed components of DBD via UPLC-Q/TOF-MS. A multi-omics approach combining metabolomics, molecular docking, and dynamics simulations was utilized to identify therapeutic targets and bioactive components, followed by experimental validation using pharmacological assays, Western blot, and cellular thermal shift assay (CETSA). Results In the BDS mouse model, DBD primarily corrected nicotinate and nicotinamide metabolism and improved hematopoietic function. Furthermore, it significantly decreased the levels of inflammatory cytokines that activate the STAT3 signaling pathway, including interleukin-6 (IL-6), interleukin-17 (IL-17), and transforming growth factor-β (TGF-β). It also suppressed the expression of p-JAK2/JAK2 and p-STAT3/STAT3. Under the effective status of DBD, we identified eleven prototype components and three metabolites derived from DBD, among which astragaloside IV was a high-affinity binder to STAT3, with molecular dynamics simulations and CETSA confirming its binding stability. Conclusion Our integrated approach suggests that DBD may alleviate BDS by normalizing metabolic imbalance and suppressing the IL-6/JAK2/STAT3 signaling pathway. A role for astragaloside IV as a potent bioactive compound of DBD with high-affinity binder to STAT3 is supported by molecular dynamics simulations and CETSA experiments. These findings provide a mechanistic foundation for DBD's therapeutic effects in treating BDS.
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DOI
PubMed
高影响因子
Food Science & Nutrition
·
2021
·Vol. 9
·期 7
·3722-3731
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IF 2.863
Lin Zhu,Yingjuan Liu,Xiaolin Wu,Yuqian Ren,Qinghua Zhang,Leiming Ren,Yunliang Guo
Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo , CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.
研究领域:
神经科学
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衰老研究
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药理学
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 4
·237
·
IF 4.5
Han Zhipeng,Li Xing,Yang Li,Li Jinglin,Zhao Kaiyang,Xie Junxiong,Zhou Siyuan,Shi Wenli,Zhang Xiaolina
Neuropathic pain (NP) is chronic pain caused by injury or disease affecting the nervous system. SIN@Lip-HA was prepared and characterised for particle size, zeta potential, encapsulation efficiency and morphology. Sprague-Dawley rats with spared nerve injury (SNI) were randomly divided into the six groups. Analgesic effects were assessed via behavioural tests. Histopathological changes were examined using H&E staining. Astrocyte polarisation was detected using immunofluorescence, and Western blotting was used to assess related protein expression. qRT-PCR measured mRNA level of genes, while ELISA evaluated inflammatory cytokines and oxidative stress markers. The study showed that the particle size of SIN@Lip-HA was 111 ± 5.13 nm, with an encapsulation efficiency of 85.47% and a zeta potential of -24.86 ± 1.20 mV. The in vitro release profile showed sustained drug release, and the formulation remained stable for 3 months. Compared with the model group, SIN@Lip-HA significantly increased PWT and PWL, alleviated spinal cord pathology and was associated with a shift in astrocyte reactivity, as indicated by a reduction in A1-related markers and an increase in A2-related markers. SIN@Lip-HA downregulated CGRP/SP and GFAP. It was also found to inhibit JAK2/STAT3 pathway activation by reducing p-JAK2/p-STAT3 expression and decrease TNF-α, IL-1β and IL-6 whilst increasing IL-10. It also mitigated oxidative stress. Concomitant use with gabapentin markedly enhanced therapeutic efficacy. These findings suggest that sinomenine liposomes alleviate NP in SNI rats in a manner associated with inhibition of JAK2/STAT3 signaling and correlated with astrocyte reactivity, and reduced pain mediators.
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yu Wang,Meihao Peng,Xin Yang,Liming Tu,Jiamin Liu,Yixi Yang,Rui Li,Xue Tang,Yuqing Hu,Guowu Zhang,Qi Zhao,Qiuxia Lu
ABSTRACT Ethnopharmacological relevance Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. Aim of the study This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. Materials and methods The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAs-FCD in inhibiting M2 macrophage polarization in the context of allergic asthma. Results A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1,756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1β, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL-1β, TNF-α and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. Conclusion TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice.
研究领域:
药理学
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免疫学
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呼吸医学
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中医药
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xingfan Li,Rong Ji,Linyan Duan,Zhizhong Hao,Yujing Su,Hao Wang,Fangxia Guan,Shanshan Ma
The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.
研究领域:
神经科学
·
生物材料
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再生医学
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炎症
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jing Guo,Qi-Yun Zhang,Lin Xu,Min Li,Qian-Yun Sun
Acute lung injury (ALI) is an acute respiratory-related progressive disorder, which lacks specific pharmacotherapy. Icariin (ICA) has been shown to be effective in treating ALI. However, the targets and pharmacological mechanisms underlying the effects of ICA in the treatment of ALI are relatively lacking. Based on network pharmacology and molecular docking analyses, the gene functions and potential target pathways of ICA in the treatment of ALI were determined. In addition, the underlying mechanisms of ICA were verified by immunohistochemistry, immunofluorescence, quantitative Real-time PCR, and Western blot in LPS-induced ALI mice. The biological processes targeted by ICA in the treatment of ALI included the pathological changes, inflammatory response, and cell signal transduction. Network pharmacology, molecular docking, and in vivo experimental results revealed that ICA inhibited the complement C5a-C5aR1 axis, TLR4 mediated NF-κB, MAPK, and JAK2-STAT3 signaling pathways related gene and protein expressions, and decreased inflammatory cytokine, chemokine, adhesion molecule expressions, and mitochondrial apoptosis in LPS-induced ALI.
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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呼吸医学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2023
·
IF 10.7
Yujun Wu,Xiangyu Zhang,Xiaoyi Liu,Yi Li,Dandan Han,Yu Pi,Melanie A. Whitmore,Xingmiao Lu,Guolong Zhang,Jinkai Zheng,Junjun Wang
Introduction Galactooligosaccharides (GOS) are lactogenic prebiotics that exert health benefits by stimulating the growth of different Lactobacillus strains in the gastrointestinal (GI) tract. Objectives This study aimed to investigate the mechanism of action of different GOS-enriched lactobacilli in intestinal health. Methods Piglets and mice were supplemented with GOS to identify specific enrichment of Lactobacillus . The protective effects of individual GOS-enriched lactobacilli were investigated in Salmonella -infected mice. Macrophage depletion and transcriptome analysis were further performed to assess the involvement of macrophages and the underlying mechanisms of individual lactobacilli. An in vitro cell co-culture system was also used to evaluate the anti-adhesive and anti-invasive activities of lactobacilli against Salmonella in epithelial cells. Results GOS markedly increased the relative abundance of three lactobacilli including L. delbrueckii , L. johnsonii , and L. reuteri in both piglets and mice. Supplementation with GOS further alleviated Salmonella infection in mice. L. delbrueckii (ATCC®BAA 365™), but not L. johnsonii or L. reuteri , enhanced propionate production in the intestinal tract and ameliorated Salmonella -induced intestinal inflammation and barrier dysfunction by suppressing the JAK2-STAT3 signaling and M1 macrophage polarization. L. johnsonii (BNCC 186110), on the other hand, inhibited Salmonella adhesion and invasion of epithelial cells through competitive exclusion. However, L. reuteri (BNCC 186135) failed to protect mice against Salmonella infection. Conclusion GOS-enriched lactobacilli show a differential role in protecting against Salmonella -induced intestinal barrier dysfunction and inflammation. Our results provide novel insights into the mechanism of action of GOS and individual Lactobacillus strains in the control and prevention of intestinal inflammatory disorders.
研究领域:
微生物学
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免疫学
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营养科学
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胃肠病学
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DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2025
·
IF 4.9
Yang Liu,Quanwei Sun,Xuefei Xu,Mengmeng Li,Wenheng Gao,Yunlong Li,Ye Yang,Dengke Yin
Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus , and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo . Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
研究领域:
免疫学
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分子生物学
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药理学
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炎症性肠病研究
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信号转导
✓ 已验证
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）