Polymers
·
2025
·Vol. 17
·期 14
·1900
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IF 4.9
Guoying Zhou,Yujia Yan,Linh Nguyen,Jiangkai Fan,Xiao Zhang,Li Gan,Tingzi Yan,Haitong Wan
Traumatic brain injury (TBI) leads to severe neurological dysfunction, disability, and even death. Surgical intervention and neurorehabilitation represent the current clinical management methods, yet there remains no effective treatment for recovery after TBI. Post-traumatic hyperinflammation and vascular injury are the key therapeutic challenges. Therefore, a novel-designed multifunctional HT/SAA/HSYA hydrogel based on hyaluronic acid (HA) co-loaded with salvianolic acid A (SAA) and hydroxysafflor yellow A (HSYA) was developed in order to simultaneously target inflammation and vascular injury, addressing key pathological processes in TBI. The HT hydrogel was formed through covalent cross-linking of tyramine-modified HA catalyzed by horseradish peroxidase (HRP). Results demonstrated that the HT hydrogel possesses a porous structure, sustained release capabilities of loaded drugs, suitable biodegradability, and excellent biocompatibility both in vitro and in vivo. WB, immunofluorescence staining, and PCR results revealed that SAA and HSYA significantly reduced the expression level of pro-inflammatory cytokines (IL-1β and TNF-α) and inhibited M1 macrophage polarization through the suppression of the TLR4/NF-κB inflammatory pathway. In vivo experiments confirmed that the HT/SAA/HSYA hydrogel exhibited remarkable pro-angiogenic effects, as evidenced by increased expression of CD31 and α-SMA. Finally, H&E staining showed that the HT/SAA/HSYA hydrogel effectively reduced the lesion volume in a mouse TBI model, and demonstrated more pronounced effects in promoting brain repair at the injury site, compared to the control and single-drug-loaded hydrogel groups. In conclusion, the HT hydrogel co-loaded with SAA and HSYA demonstrates excellent anti-inflammatory and pro-angiogenic effects, offering a promising therapeutic approach for brain repair following TBI.
研究领域:
神经外科学
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生物材料学
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免疫学
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药理学
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再生医学
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METABOLIC BRAIN DISEASE
·
2026
·Vol. 41
·期 1
·104
·
IF 3.8
Zhong Guangcheng,Shi Jiahui,Jiang Yue,Li Shiyin,Wang Xuejing,Zhang Ting,Chen Zhuo,Wang Qi,Liu Shan
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition distinguished by intricate pathological mechanisms. Cinnamaldehyde, a natural active chemical sourced from the bark of Cinnamomum species, exhibits remarkable neuroprotective properties that have been validated in various neurological disorders. In this study, network pharmacology alongside zebrafish experiments was employed to investigate the molecular mechanisms and signaling pathways through which cinnamaldehyde ameliorates AD. Potential targets of cinnamaldehyde were found using the SuperPred, TargetNet, SwissTargetPrediction, and SEA databases, whilst AD-related targets were obtained from TTD, OMIM, GeneCards, and DrugBank databases. Subsequently, protein-protein interaction analysis was performed using the STRING database, followed by GO and KEGG enrichment studies via the DAVID platform. Finally, molecular docking validation was conducted using CB-Dock2. The network pharmacology results indicated that cinnamaldehyde might impact its beneficial effects on AD via regulating the toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) signaling pathway. To further validate this mechanism, an AD model was established in zebrafish induced by aluminum chloride (AlCl₃). Behavioral assays demonstrated that cinnamaldehyde significantly improved AlCl₃-induced cognitive impairment. Hematoxylin-eosin and Nissl staining revealed that cinnamaldehyde attenuated neuropathological damage. Biochemical analyses indicated that cinnamaldehyde alleviated oxidative stress and restored cholinergic dysfunction. Furthermore, RT-qPCR findings indicated that cinnamaldehyde reduced inflammatory mediator expression and diminished TLR4 and NF-κB p65 mRNA levels, while western blotting confirmed reduced TLR4 and phosphorylated NF-κB p65 protein expression. In summary, cinnamaldehyde may mitigate neuroinflammation through suppressing the TLR4/NF-κB signaling pathway, thereby ameliorating AlCl₃-induced cognitive impairment, neuropathological injury, oxidative stress imbalance, and cholinergic system dysfunction in zebrafish. Graphical The alternative text for this image may have been generated using AI.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
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2020
·Vol. 72
·期 7
·956-968
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IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
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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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wenqian Wang,Qingfu Zhang,Tong Zhang,Fuping Lu,Fufeng Liu
Current therapeutic options for Parkinson's disease (PD) are limited in efficacy and burdened with severe side-effects. Inflammation, intertwined with oxidative stress and influenced by gut microbiota-related changes making the gut-brain axis the main target of innovative therapies. This study reveals the multiple protective effects of polysaccharides extracted from Ulva lactuca (UPE) on PD models. In vitro, UPE was shown to have direct cytoprotective effects, including mitigating 1-methyl-4-phenylpyridinium-induced cell apoptosis, reducing reactive oxygen species levels, and maintaining mitochondrial membrane potential. In vivo, oral UPE significantly restored motor deficits and dopaminergic neuron loss caused by MPTP. These in vivo benefits were associated with the inhibition of oxidative stress and inflammation. Moreover, oral UPE inhibits the excessive activation of glial cells and the excessive production of pro-inflammatory factors and oxidative stress markers in serum. Furthermore, 16S rRNA analysis of gut microbiota revealed that UPE reshaped the gut microbiota of PD mice by increasing the abundance of norank_f_Murbaculaceae and decreasing the abundance of Desulfovibrio . Mechanically, the Nrf2/HO-1 and TLR4/NF-κB signaling pathways are involved in the anti-PD effect of UPE. In general, UPE offers new perspectives on PD treatment and demonstrates the potential of natural polysaccharides in treating neurodegenerative diseases.
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Advanced Healthcare Materials
·
2024
·
IF 10
Jiahao Wang,Liang Zhang,Lingjun Wang,Jincheng Tang,Wei Wang,Yichang Xu,Ziang Li,Zhouye Ding,Xinzhao Jiang,Kun Xi,Liang Chen,Yong Gu
Targeting macrophages can facilitate the site-specific repair of critical bone defects. Herein, a composite hydrogel, gelatin- Bletilla striata polysaccharide-mesoporous bioactive glass hydrogel (GBM gel ), is constructed via the self-assembly of mesoporous bioactive glass on polysaccharide structures, through the Schiff base reaction. GBM gel can efficiently capture macrophages and drive the recruitment of seed stem cells and vascular budding required for regeneration in the early stages of bone injury, and the observed sustained release of inorganic silicon ions further enhances bone matrix deposition, mineralization, and vascular maturation. Moreover, the use of macrophage-depleted rat calvarial defect models further confirms that GBM gel , with ligand-selective macrophage targeting, increases the bone regeneration area and the proportion of mature bone. Mechanistic studies reveal that GBM gel upregulates the TLR4/NF-κB and MAPK macrophage pathways in the early stages and the JAK/STAT3 pathway in the later stages; thus initiating macrophage polarization at different time points. In conclusion, this study is based on the endogenous self-healing properties of bone macrophages, which enhances stem cell homing, and provides a research and theoretical basis upon which bone tissue can be reshaped and regenerated using the body's immune power, providing a new strategy for the treatment of critical bone defects.
研究领域:
生物医学工程
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组织工程
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免疫学
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再生医学
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材料科学
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POULTRY SCIENCE
·
2026
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IF 4.5
Dan Shao,Longqing Hu,Wei Guo,Jinglong Chen,Xuming Guo,Hong Yao
This study aimed to investigate the protective effect and mechanism of dietary dimethylglycine (DMG) on jejunal injury in yellow-feathered broilers subjected to cyclic heat stress (HS). A total of 180 35-day-old male yellow-feathered broilers were randomly allocated into 3 groups: the thermoneutral condition with basal diet group (CON), the cycle heat stress with basal diet group (HS, 32-35°C), and the cycle heat stress with 0.1% DMG in basal diet group (HS_DMG, 32-35°C). The experiment included a 7-day heating period followed by a 14-day cyclic heat stress period. Growth performance, rectal temperature, jejunal morphology and ultrastructure, inflammatory cytokine levels, and protein expression related to the TLR4/NF-κB pathway and MUC2 were evaluated. Additionally, primary chicken jejunal epithelial cells were isolated and exposed to heat stress with or without DMG pretreatment to validate in vivo findings. Results showed that heat stress significantly increased rectal temperature ( P < 0.05), had a tendency to reduce body weight (BW, P = 0.058) and average daily gain (ADG, P = 0.050), and increase the feed-to-gain ratio (F/G, P = 0.053). Histologically, HS caused epithelial shedding, reduced villus height and villus height/crypt depth, and induced microvilli damage and mitochondrial swelling, all of which were attenuated by DMG supplementation. Heat stress also elevated jejunal mucosa levels of IL-6, IL-8, IL-1 β , and TNF- α ( P < 0.05), while DMG reduced IL-6, IL-8, and TNF- α ( P < 0.05). Immunohistochemistry and western blotting revealed that HS decreased MUC2 expression and increased TLR4 and p-NF-κB-p65 protein levels ( P < 0.05), whereas DMG reversed these changes ( P < 0.05). In vitro, DMG pretreatment alleviated HS-induced reduction in inflammatory cytokine release, and alterations in TLR4, NF-κB, and MUC2 protein expression. In conclusion, dietary DMG supplementation alleviates cyclic heat stress-induced jejunal injury in yellow-feathered broilers by suppressing the TLR4/NF-κB signaling pathway and restoring MUC2 expression.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
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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International Journal of Nanomedicine
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2024
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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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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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Current Pharmaceutical Analysis
·
2026
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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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NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 2
·129
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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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Cell Death Discovery
·
2025
·Vol. 11
·期 1
·1-15
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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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