INTERNATIONAL IMMUNOPHARMACOLOGY
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2019
·
IF 3.361
Sen Yang,Ge Kuang,Rong Jiang,Shengwang Wu,Tao Zeng,Yuanyuan Wang,Fangzhi Xu,Lingyi Xiong,Xia Gong,Jingyuan Wan
Acetaminophen (APAP) is a widely used over-the-counter drug for antipyretic and analgesic , but an overdose will induce acute liver injury. APAP hepatotoxicity has been the most common cause of acute liver failure in western countries with high morbidity and mortality. Geniposide (GP), an iridoid glycoside extracted from the fruit of Gardenia jasminoides , has been reported to exert a profound anti-inflammatory activity on acute and chronic diseases. However, it is never demonstrated whether GP can protect hepatocytes from APAP hepatotoxicity. In this study, we investigated the protective effect and underlying mechanism of GP against AILI. The results showed that GP pretreatment reduced the levels of ALT and AST in a dose-dependent manner and alleviated hepatocyte necrosis and apoptosis in mice exposed at APAP. Moreover, it suppressed the expression of CYP 2E1 and attenuated the exhaustion of GSH and accumulation of MDA in the liver. Furthermore, GP remarkably inhibited inflammatory cells infiltration and mitigated the release of IL-1β and TNF-α, and inhibited Toll-like receptor 4 (TLR4) expression and nuclear factor kappa (NF-κB) activation. These data suggested that GP could effectively protect hepatocytes from APAP hepatotoxicity through the down-regulation of CYP 2E1 expression and the inhibition of TLR4/NF-κB signaling pathway .
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PLoS One
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2015
·Vol. 10
·期 2
·e0116879
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IF 3.234
Li Zhang,Yuanyuan Li,Zhiwen Gu,Yuyue Wang,Mei Shi,Yun Ji,Jing Sun,Xiaopeng Xu,Lirong Zhang,Jingtin Jiang,Weifeng Shi
Polydatin and resveratrol, as major active components in Polygonum cuspidatum , have anti-inflammatory, antioxidant and antitumor functions. However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71) have not been reported. In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect. Neither polydatin nor resveratrol exhibited influence on viral attachment. Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKβ, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively. Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD) cells could be blocked by resveratrol. These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway. Thus, resveratrol may have potent antiviral effect on EV71 infection.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Fengjiao Liu,Yaxin Jia,Liwei Zhao,Li-na Xiao,Xizhen Cheng,Yingying Xiao,Ying Zhang,Yuling Zhang,Huimin Yu,Qiao-en Deng,Yuanyuan Zhang,Yimeng Feng,junfang Wang,Yonggang Gao,Xuan Zhang,Yunyun Geng
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
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Food & Function
·
2025
·
IF 5.4
Xiaoran Kong,Li Zhao,He Huang,Qiaozhen Kang,Jike Lu,Jia-Qing Zhu
Hyperuricemia is chronic metabolic disease with a high incidence, and it has become the “fourth highest” health risk in modern times. Isorhamnetin is a natural flavonoid found in a variety of plants, especially fruits such as buckthorn. In vivo hyperuricemia ameliorating effect of isorhamnetin and the specific molecular mechanism were profoundly investigated through a hyperuricemia mice model in the present study. The results demonstrated that isorhamnetin showed a significant uric acid-lowering effect in mice. Isorhamnetin was able to reduce uric acid production by inhibiting XOD activity. On the other hand, it reduced the expression of GLUT9 to inhibit uric acid reabsorption and enhanced the expression of ABCG2, OAT1, and OAT3 to promote uric acid excretion. Metabolomics analysis revealed that isorhamnetin gavage restored the purine metabolism and riboflavin metabolism disorders, and thus significantly alleviated the hyperuricemia in mice. Further, the alleviating effect of isorhamnetin on hyperuricemia-induced renal inflammation and its specific mechanism were explored through network pharmacology and molecular validation experiments. Network pharmacology predicted that seven targets were enriched in the PI3K/AKT pathway (CDK6, SYK, KDR, RELA, PIK3CG, IGF1R, MCL1) and four targets were enriched in the NF-κB pathway (SYK, PARP1, PTGS2, RELA). Western blot validated that isorhamnetin inhibited the phosphorylation of PI3K and AKT and down-regulated the expression of NF-κB p65. It indicated that isorhamnetin could inhibit the PI3K/AKT/NF-κB signaling pathway to reduce the levels of renal inflammatory factors (TNF-α, IL-β and IL-6) and ultimately ameliorate the hyperuricemia-induced renal inflammation in mice. This study will provide comprehensive and penetrating theoretical basis for the application of isorhamnetin in the field of functional foods or dietary supplements to improve hyperuricemia.
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CTS-Clinical and Translational Science
·
2024
·Vol. 17
·期 3
·e13748
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IF 3.1
Chenyu Song,Kaiyang Wang,Bangping Qian,Jingshun Lu,Mu Qiao,Yong Qiu,Bin Wang,Yang Yu
Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti-inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS-MSCs, we found that the expression levels of p-NF-κB, IL-6, IL-1β, and TNF-α were higher and IκB-α, Nrf-2, and HO-1 were lower compared with healthy control (HC)-MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1-Nrf-2 and p65-IκB-α were predicted. The mRNA and protein expression of p-NF-κB, IL-6, IL-1β, and TNF-α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB-α, Nrf-2, and HO-1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS-MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf-2/ROS/NF-κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS.
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HISTOLOGY AND HISTOPATHOLOGY
·
2024
·
IF 2.5
Shuang Bai,Shao-Kang Sun,Zhen-Qi Xu,Ying-Bin Yan
Objective: Accumulating evidence has implicated matrix metalloproteinases (MMPs) in the progression of human cancers. Matrix metallopeptidase 25 (MMP25) is a membrane-type MMP whose role in tumorigenesis and cancer development is not well understood. Here, we investigated the functions of MMP25 in tongue squamous cell carcinoma (TSCC). Methods: Gene expression was measured using real-time PCR and western blot. CCK-8 and Transwell assays were used to determine the proliferation, migration, and invasion of TSCC cells. An NK cell co-culture experiment was performed to evaluate the killing of TSCC cells by NK cells. Results: MMP25 had higher expression levels in TSCC tissues than in adjacent non-cancerous tissues. MMP25-overexpressing and MMP25-silenced TSCC cell lines were established by lentiviral transduction. Overexpression of MMP25 promoted proliferation, migration, and invasion of TSCC cells, whereas knockdown of MMP25 had opposite effects. MMP25 modulated the levels of proliferation- and apoptosis-related proteins (PCNA, cyclin D, cyclin B1, p27, and cleaved caspase 3 and 9) and upregulated two invasion-related MMPs (mature MMP2 and MMP9). Additionally, MMP25 promoted tumor growth of TSCC cells in athymic nude mice. Notably, MMP25 upregulated PD-L1 in TSCC cells, attenuated NK cell killing of TSCC cells, and inhibited the secretion of anti-tumor cytokines (TNF-α and IFN-γ). Furthermore, MMP25 promoted the nuclear translocation of NF-κB p65, suggesting that activation of NF-κB signaling may mediate the pro-tumor functions of MMP25 in TSCC. Conclusion: This study revealed a novel role for MMP25 in TSCC, highlighting the potential of MMP25 as a therapeutic target in TSCC.
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EUROPEAN JOURNAL OF NUTRITION
·
2024
·Vol. 64
·期 1
·1-13
·
IF 4.1
Han Ning,Li Jie,Li Yangyang,Zhao Feiei,Wang Jun,Ye Peiyu,Zeng Zhenling
Ethnopharmacological relevance Xanthohumol (XN), an isoprenylated flavonoid natural product found only in hops, possesses a variety of biological activities such as anticancer, anti-inflammatory, hepatoprotective, and anti-obesity. Aim of the study The aim of this study was to investigate the effects and mechanisms of XN on the treatment of colitis. Materials and methods First, acute colitis was induced by using distilled water containing 3% DSS for 10 consecutive days. The therapeutic efficacy of XN was assessed by an established DSS-induced mouse colitis model. Subsequently, disease activity index (DAI) and colon length of mice were assessed. The health of the intestines was assessed by histopathological analysis. Inflammatory factors, IL-1β, IL-6, and TNF-α, were detected in colon tissues by ELISA.Finally, mouse intestinal contents were extracted and subjected to 16 S rRNA Sequencing, and the gut microbiota was analysed for Alpha-diversity and Beta-diversity. Results The results showed that XN ameliorated DSS-induced colitis. Furthermore, XN reduced pro-inflammatory cytokine levels such as IL-1β, IL-6, and TNF-α, as well as inhibited the activation of the TLR4/NF-κB pathway, all of which helped to mitigate the inflammatory response. Finally, we also found that XN alleviated intestinal dysbiosis in colitis mice. Conclusion In conclusion, our study demonstrated that XN provides protective effects against colitis, and has the potential to be further explored as a lead compound for the treatment of inflammatory bowel disease (IBD). Graphical
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Pharmaceuticals
·
2025
·Vol. 18
·期 8
·1109
·
IF 4.8
Lingxin Zhuo,Mingxuan Ma,Jiayi Zhang,Jiayu Zhou,Yuqi Zheng,Aiyin Liang,Qingqing Sun,Jia Liu,Wenting Liao
Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC.Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models.Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2.Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment.
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Song-Xue Yang,Wei-Lie Xiao,Xing-Jie Zhang
Ethnopharmacological relevance The root of Saposhnikovia divaricata has been traditionally used in Chinese medicine to treat inflammation and immune related skin diseases, such as skin allergy and itchy rash. However, scientific research supporting its efficacy, particularly in curing inflammation from acne, is still scarce. Aim of the study To evaluate the therapeutic effects of essential oil of Saposhnikovia divaricata (EOSD) on Cutibacterium acnes ( C. acnes )-induced acne and investigate its mechanisms. Materials and Methods An acute acne model was established by injecting C. acnes into mouse ears, followed by topical EOSD treatment (0.25 %, 0.5 % and 1 %). Ear tissues were analyzed 24 hours post-treatment. In vitro, C. acnes -stimulated J774A.1 macrophages were treated with EOSD (3, 10 and 30 μg/ml) to assess mitochondrial damage, oxidative stress, and inflammatory responses. Key markers were analyzed using electron microscopy, real-time PCR, immunoblotting, ELISA, and immunofluorescence. Nrf2 knockdown was achieved via siRNA transfection. Results C. acnes suppressed Nrf2 activation, increased ROS levels, and triggered NLRP3 inflammasome activation, leading to inflammation. EOSD restored Nrf2 activity, reduced ROS levels, and inhibited NLRP3 activation. In vitro, EOSD disrupted Nrf2/Keap1 interaction, enhanced Nrf2 nuclear translocation, reduced mitochondrial damage, and suppressed pyroptosis by downregulating IL-1β, Caspase-1, GSDMD, and NF-κB signaling. These effects were reversed by Nrf2 knockdown. Conclusion EOSD alleviates oxidative stress and modulates NLRP3 inflammasome activation through upregulating Nrf2 pathway and inhibiting NF-κB pathway, as well as improving mitochondrial homeostasis and inflammatory responses in acne. These findings suggest that EOSD may be a promising therapeutic agent for the treatment of acne vulgaris.
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WORLD JOURNAL OF GASTROENTEROLOGY
·
2025
·Vol. 31
·期 34
·109825
·
IF 5.4
Peng-Tuo Xiao,Chang-Feng Li,Yuan-Da Liu,Jing Zhong,Xi-Lun Cui,Chang Liu,Wei Yang
BACKGROUND Colorectal cancer (CRC) is a major global health burden. B cell CLL/lymphoma 10 (BCL10), a key component of the caspase recruitment domain protein-BCL10-mucosa-associated lymphoid tissue lymphoma paracaspase complexes, is upregulated in CRC and associated with poor patient prognosis, suggesting its potential role in CRC development and progression. Cuproptosis, a novel form of programmed cell death, has emerged as a promising therapeutic strategy for cancer. AIM To explore the role of BCL10 in regulating the sensitivity of CRC cells to cuproptosis. METHODS A series of in vitro and in vivo experiments were conducted using CRC cell lines and CRC mouse models to evaluate the effects of BCL10 on CRC cell proliferation, migration, invasion, and sensitivity to copper-induced cell death. Mechanistic studies were performed to elucidate the underlying molecular pathways. RESULTS BCL10 promoted CRC cell proliferation, migration, and invasion, while its knockdown had the opposite effects. BCL10 also influenced the sensitivity of CRC cells to cuproptosis, with BCL10 overexpression enhancing resistance and its knockdown increasing sensitivity. The mechanism involved BCL10 modulating the expression of DLAT, a key protein in the copper-induced cell death pathway, through activation of the nuclear factor kappa-B (NF-κB) signaling pathway. CONCLUSION BCL10 promotes CRC growth and regulates the sensitivity of CRC cells to cuproptosis by activating the NF-κB signaling pathway and modulating DLAT expression. These findings provide a molecular basis for developing BCL10-targeted therapies for CRC.
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Bioactive Materials
·
2025
·
IF 20.3
Jieying Liu,Fuze Liu,Cairong Li,Zhengyao Li,Tianle Li,Yuanhao Wu,Di Wu,Yue Huang,Hui Chen,Hai Wang,Yuxiao Lai,Zhihong Wu
Background Iron oxide nanoparticles (IONPs)-based bone scaffolds have attracted increasing attention because of their potential to enhance osteogenesis and angiogenesis. However, the underlying mechanisms remain incompletely understood. Methods We fabricated a biocompatible bone scaffold by incorporating γ-Fe 2 O 3 magnetic nanoparticles into a PLGA matrix using 3D printing technology. The biosafety and effectiveness of the scaffold was validated through in vitro cell assays and in vivo implantation studies. To evaluate osteogenesis and neovascularization, we employed micro-CT imaging with a vascular contrast agent. In-depth mechanistic investigations were conducted via label-free proteomic profiling and pathway enrichment analysis. Results The PLGA/Fe 2 O 3 scaffolds demonstrated excellent biocompatibility and promoted both bone formation and angiogenesis in vitro and in vivo . Micro-CT analysis revealed enhanced new bone and vessel formation in the presence of magnetic scaffolds. Proteomic analysis revealed that alpha-B crystallin (CRYAB) is a key regulatory protein upregulated under a static magnetic field, thereby activating the PI3K/AKT signaling cascade and promoting osteogenic differentiation. In endothelial cells, we observed the upregulation of nuclear NF-κB and HIF-1α, leading to VEGF expression and angiogenic activation. Conclusion Our findings provide direct evidence that 3D-printed PLGA/Fe 2 O 3 scaffolds promote osteogenesis and angiogenesis both in vitro and in vivo . Importantly, we report for the first time that CRYAB-mediated stabilization of β-catenin plays a central role in magnetic scaffold-induced bone regeneration, offering new insights into the design of functional bone substitutes.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Sezhen Quni,Yidi Zhang,Lijun Liu,Manxuan Liu,Lu Zhang,Jiaqian You,Jing Cui,Xiuyu Liu,Hanchi Wang,Daowei Li,Yanmin Zhou
The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π–π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.
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