JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Tingting Yan,Jinghe Sun,Yuying Zhang,Chengrong Wen,Jingfeng Yang
Enteromorpha prolifera polysaccharide (EP2) protection against acute alcoholic liver injury (AALI) in mice was investigated. By integration of physiological indicators, gut microbiota, and short-chain fatty acids (SCFAs), the mechanism of EP2 in alleviating AALI was disclosed. The results showed that EP2 significantly ameliorated alcohol-induced abnormal transaminase activities, liver and intestinal systemic inflammation, and intestinal environmental disorders. EP2 significantly reduces liver and serum LPS contents by 1.69-fold and 1.54-fold. Furthermore, inhibition of the NF-κB signaling pathway by EP2 reduced the production of proinflammatory cytokines such as TNF-α (1.83-fold), IL-6 (11.09-fold), and IL-1β (1.99-fold). EP2 restored SCFAs to normal levels by upregulating the abundance of beneficial bacteria (Colidextribacter, Ruminococcus, unclassified_Lachnospiraceae, and Akkermansia). The alleviation of AALI by EP2 occurs through protection of the intestinal mucosal barrier and reduction of LPS permeating in serum. The decrease in LPS inactivates the NF-κB signaling pathway and prevents inflammation. In short, EP2 regulates the gut–liver axis and inflammation, alleviating effects in AALI mice.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yingying Song,Xiaojuan Zhang,Xinyan Han,Gaorui Wang,Mengxue Wang,Hui Wu,Xiaojun Wu
Ethnopharmacological relevance The traditional Chinese herb Panax ginseng recorded in "Shennong Herbal Classic" is renowned for its purported vascular regulatory properties and immune-enhancing capabilities. Ginsenoside Rb1 (Rb1), a prominent bioactive compound in Panax, has demonstrated significant neuropharmacological activities. However, its impact on multiple sclerosis (MS) and blood-brain barrier (BBB) damage remains inadequately investigated. Aim of the study Inflammation and BBB disruption are pivotal to MS. Tightly packed brain capillary endothelial cells are fundamental to the structural and functional integrity of the BBB. Rb1 has been shown to alleviate BBB damage in stroke rats, but its effect on BBB damage in MS is not well understood. The objective of this study was to examine the role and mechanism of Rb1 on BBB injury in experimental autoimmune encephalomyelitis (EAE) mice. Materials and methods The BBB protection effect and mechanism of Rb1 were evaluated in LPS-treated bEnd.3 cells and EAE model mice. The mRNA expression levels of the inflammatory factor and the protein expressions of matrix metalloproteinases 9 (MMP9), zona occludens 1 (ZO-1), inhibitor of NF-κB (IκBα), occludin, Jun-amino-terminal kinase (JNK), and nuclear factor-κB (NF-κB) in bEnd.3 cells and mouse cerebral cortex were quantified. The permeability of bEnd.3 cells was examined by measuring trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. Results Rb1 administration in the early stages of EAE postponed the disease's onset and lessened its severity. Rb1 inhibited the destruction of the BBB in brain cortex of EAE mice. Rb1 reduced the lipopolysaccharide (LPS)-induced hyperpermeability of bEnd.3 cells and prevented the downregulation of TJ proteins. In addition, in LPS-induced bEnd.3 cells, Rb1 decreased the overproduction of reactive oxygen species. Moreover, Rb1 suppressed the phosphorylation of JNK, ERK, NF-κB, and IκB in vivo and in vitro. Furthermore, the JNK agonist anisomycin was observed to partially abolish the protective effect of Rb1 in bEnd.3 cells treated with LPS. Conclusions Taken together, we demonstrated that Rb1 improved demyelination and BBB damage in EAE mice by modulating JNK/ERK/NF-κB signaling pathway. This study can offer a theoretical foundation for the use of Rb1 in the treatment of EAE by preventing BBB injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-19
·
IF 6.1
Qin Qian,Shan Zhiyan,Xing Lei,Jiang Yutong,Li Mengyue,Fan Linlin,Zeng Xin,Ma Xinrui,Zheng Danyang,Wang Han,Wang Hui,Liu Hao,Liang Shengjun,Wu Lijie,Liang Shuang
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Bingyan Gu,Yuying Chen,Huifang Xu,Kunyu Zhan,Keying Zhu,Huan Luo,Yanqun Huang,Hanbing Zeng,Wenbiao Zheng,Kun Tian,Hongfeng Ruan
Purpose Chlorpyrifos (CPF), a widely used organophosphate pesticide in agriculture, particularly in China, has raised significant environmental and health concerns due to its persistence and bioaccumulation. While CPF-induced toxicity in multiple organ systems has been documented, its long-term impact on thyroid homeostasis and the underlying mechanisms remain poorly understood. This study aimed to investigate the subchronic effects of CPF on thyroid function and elucidate the underlying mechanisms of CPF-induced thyroid toxicity.Methods The study utilized 4-week-old male C57BL/6J mice as experimental subjects. These mice were exposed to CPF via intragastric gavage at doses of 3 or 6 mg/kg for a duration of 8 weeks. Throughout the study period, various parameters were assessed, including body weight, serum antioxidant capacity, thyroid endocrine function and structure, apoptosis markers, inflammatory cytokines, and relevant molecular pathways.Results The study revealed that CPF exposure resulted in significant systemic toxicity, manifested through reduced body weight and impaired serum antioxidant capacity. Examination of thyroid-specific effects showed disrupted thyroid endocrine function and structure, accompanied by increased apoptosis and elevated inflammatory cytokines. At the molecular level, CPF significantly stimulated thyroid follicle cell pyroptosis by upregulating the expression of Nlrp3, Caspase-1, and Gsdmd. Further mechanistic analysis demonstrated that CPF activated thyroid follicular cell pyroptosis by modulating the Nrf2/Keap1 antioxidative pathway and enhancing phosphorylation of p65 via NF-κB signaling.Conclusion This comprehensive investigation provides novel insights into the mechanisms of CPF-induced thyroid toxicity. The findings demonstrate that CPF exposure compromises thyroid homeostasis through the induction of follicular cell pyroptosis and modulation of the Nrf2/Keap1/NF-κB signaling axis, highlighting the potential health risks associated with CPF exposure and its impact on thyroid function.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 16
·e70906
·
IF 4.2
Lina Wei,Lei Wang,Yang Yu,Xiaozhou Sun,Liang Liu,Jing Han,Yongji Wang,Yinan Guo
Pediatric bacterial pneumonia continues to pose a significant global health burden, often resulting in serious complications. Recent studies have emphasized the pivotal role of the gut-lung axis in the progression of respiratory diseases, wherein disruptions in gut microbiota can aggravate pulmonary inflammation. This research investigates the underlying mechanisms by which Ma-Xing-Shi-Gan Decoction (MXSG), a classical formula in traditional Chinese medicine, influences the gut-lung axis in the context of childhood bacterial pneumonia. Clinical data indicated pronounced alterations in intestinal microbial composition and a marked decline in short-chain fatty acid (SCFA) levels among affected pediatric patients—changes that coincided with dysfunctional gut-lung signaling. In a murine model of bacterial pneumonia, MXSG administration restored microbial diversity, elevated SCFA production, and attenuated inflammatory responses by suppressing the HDAC3/NF-κB signaling cascade. Key bioactive constituents of MXSG—namely, quercetin, osajin, nobiletin, and solasodine—were identified as critical regulators, modulating lipid metabolism and promoting SCFA biosynthesis. These results highlight the therapeutic promise of MXSG in reestablishing gut-lung homeostasis and shed light on its mechanistic potential in the treatment of pediatric bacterial pneumonia. Graphical This schematic illustrates how MXSG restores gut microbiota diversity and SCFA levels, suppresses HDAC3/NF-κB signaling, and alleviates lung inflammation in pediatric bacterial pneumonia. Integrated multi-omics and mouse model experiments reveal that MXSG modulates the gut-lung axis and provides a novel mechanism for its clinical efficacy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 14
·e70659
·
IF 4.2
Hao Wang,Chi Zhang,Jinyue He,Zhuoen He,Shihua Yan,Yuan Zhang,Shiyin Huang,Yangtian Yan,Yuchi Chen,Zhiqiang Xian,Rong Hu,Yanjing Wang,Wei Xiao,Mingqing Wang
Skeletal muscle atrophy is a prevalent complication in chronic kidney disease (CKD), and its pathogenesis is closely related to inflammation and oxidative stress. P-Coumaric acid (PCA) is a phenolic acid with anti-inflammatory and antioxidant pharmacological actions. This research aims to investigate the effect of PCA on CKD-induced muscle atrophy and its underlying mechanism. In our study, in vivo and in vitro models were established by using 5/6 nephrectomized rats and LPS-induced C2C12 myoblasts. The experimental results showed that PCA ameliorated kidney injury in CKD rats and increased skeletal muscle weight and the cross-sectional area of muscle fibres. In both CKD rats and LPS-induced C2C12 myoblasts, PCA also exhibited anti-inflammatory and antioxidant effects, reduced the levels of pro-inflammatory cytokines and enhanced the activity of antioxidant enzymes. Network pharmacology studies have identified 165 common targets between PCA and skeletal muscle atrophy. Furthermore, the experimental results also demonstrated that PCA decreased the expression of TLR4, MyD88, NF-κB p65, MurF1 and MAFbx at both the protein and mRNA levels. Additionally, in vitro experiments showed that the use of TLR4 agonists could reverse the muscle-protective effect of PCA. In summary, this study illustrated that PCA ameliorated skeletal muscle atrophy in CKD rats by inhibiting the TLR4/MyD88/NF-κB pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xue-Ting Xu,Jun-Kai Fan,Xi Chen,Si-Yi Que,Run-Xin Zhang,Yu-Yan Xie,Tian-Ci Zhou,Kunmei Ji,Zhen-Fu Zhao,Jia-Jie Chen
Background Mast cells (MCs) mediate high-affinity IgE Fc receptor (FcεRI)-mediated allergic reactions. Royal jelly acid (RJA), the major lipid constituent of royal jelly, has anti-inflammatory, anti-tumor, antibacterial, and immunomodulatory properties. Purpose This study aimed to investigate how RJA affects IgE-mediated MC activation and to elucidate mechanisms underlying anti-allergic effects. Methods Mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells-2H3 (RBLs) were stimulated with IgE-antigen (Ag). β-hexosaminidase (β-hex) and histamine (HA) release, inflammatory cytokines expression, and cellular morphology changes were examined in stimulated cells. Transcriptome changes associated with RJA-treated activated-MCs were analyzed. Network pharmacology, gene expression, and western blot analyses were employed to explore the relationship between H3 lactylation and anti-allergic effects of RJA on MC. In vivo studies were conducted in IgE-mediated passive cutaneous anaphylaxis (PCA), ovalbumin (OVA)-induced active systemic anaphylaxis (ASA), and HA-induced passive systemic anaphylaxis (PSA) mouse models. Results RJA inhibited IgE-dependent MC activation as evidenced by reduced β-hex and HA release. RJA inhibited MAPK and NF-κB signaling, down-regulated RELA and NFκB1 transcripts, and decreased NF-κB reporter activity. RJA inhibited cellular H3 lactylation and H3K9 lactylation (H3K9la), leading to reduced histone lactyllysine enrichment in RELA or NFκB1 promoter loci. RJA alleviated allergic symptoms in PCA and ASA mice by intraperitoneal injection or oral administration, but did not affect HA-induced hypothermia. Conclusion RJA inhibits IgE-dependent MC activation by reducing cellular H3K9la and suppressing NF-κB signaling via reduced histone lactyllysine enrichment in RELA or NFκB1 promoter sites. RJA may support MC inhibition in the prevention and treatment of allergic diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Huiping Ou,Zhanpan Wu,Jinhua Ning,Qiufeng Huang,Wancun Wang,Guochun Yang,Yingxun Zhou,Anguo Hou,Peng Li,Lingyun Chen,Wen Bin Jin
Introduction: A series of oridonin hybrids were synthesized and evaluated for anti-inflammatory potential, focusing on their ability to inhibit NO production in RAW264.7 cells and their therapeutic prospects for NLRP3-driven disorders.Methods: Anti-inflammatory activity was assessed by measuring NO inhibition in LPS-stimulated RAW264.7 cells. The most active compound, 4c, was further analyzed using ELISA and WB to evaluate its effects on inflammatory proteins (p-NF-κB, p-IκB, NLRP3, IL-6, IL-1β, COX-2, iNOS). In vivo efficacy was tested in a murine acute lung injury model, with RT‒qPCR and WB used to assess inflammatory markers in lung tissues. Molecular docking predicted 4c’s binding mode with NLRP3, while RNA-seq and RT‒qPCR identified differentially expressed genes.Results: Compound 4c significantly inhibited NO production and suppressed key inflammatory proteins in vitro. In vivo, it alleviated acute lung injury, reduced IL-6 and TNF-α mRNA levels, and inhibited NLRP3, p-NF-κB, and IL-6 protein expression. Docking suggested covalent binding to NLRP3. RNA-seq revealed 4c upregulated Trdc, Stfa2, and Gsta2 while downregulating Spib, Csf2, and Nr4a1.Discussion: Compound 4c demonstrates potent anti-inflammatory effects via NLRP3 pathway inhibition and modulation of inflammatory genes. These findings highlight oridonin hybrids, particularly 4c, as promising candidates for NLRP3-driven inflammatory disorders, warranting further investigation.
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 46
·期 5
·806-818
·
IF 4.473
Zhi Cui,Shiqun Sun,Jia Li,Jianing Li,Tong Sha,Jie He,Linjing Zuo
Oral squamous cell carcinoma (OSCC) and hypopharyngeal squamous cell carcinoma (HSCC) are representative of head and neck squamous cell carcinoma (HNSCC) and the molecular pathogenesis has not been completely clarified. Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is the key member of the E2 family that encodes 153 amino acid residues. Previous studies demonstrate that UBE2L3 is aberrantly overexpressed in various types of human cancers, suggesting that UBE2L3 may function as an oncogene. However, its functional role and the potential mechanisms in the OSCC and HSCC remain unclear. In the present study, we found that UBE2L3 was significantly upregulated in clinical HNSCC samples and HNSCC cell lines, and patients with lower UBE2L3 expression have a higher survival rate. Two HNSCC cell lines FaDu (HSCC cells) and CAL-27 (OSCC cells) with moderate expression of UBE2L3 were selected for in vitro experiments. We proved that UBE2L3 overexpression was positively associated with cellular malignant phenotypes in vitro, including proliferation, invasion, migration, and tumor growth in vivo. Conversely, UBE2L3 suppression diametrically yielded opposing results. Our further study demonstrated that overexpression of UBE2L3 significantly activated the nuclear factor kappa B (NF-κB) signaling pathway through promoting NF-κB p65 nuclear translocation and the ubiquitination and degradation of IκBα protein. Additionally, UBE2L3 was proved to be targeted and negatively regulated by miR-378a-5p, and UBE2L3 overexpression reversed the effects of miR-378a-5p upregulation. Collectively, the present study indicates that UBE2L3 may promote OSCC and HSCC progression via activating the NF-κB signaling by increasing IκBα degradation, indicating that UBE2L3 may be a potential therapeutic target for the treatment of HNSCC.
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 22
·
IF 4.6
Bingxin Zhang,Ning Wang,Xiaoxu Chen,Nan Yang,Ying Zhao,Xiaoshu Zhang
Alcoholic liver disease (ALD) caused by excessive alcohol consumption poses a serious threat to human health.Callistephus chinensis(L.) Nees is an herb of the Asteraceae family that has good results in the prevention and treatment of a variety of liver diseases, including multifactorial liver injury, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, liver fibrosis. Sesquiterpenes are thought to be biologically active components that typically have anti-inflammatory, immunomodulatory, and cardioprotective effects. Callistephus A (CA) is a sesquiterpene compound with a rare 6/7 ring skeleton, which has been isolated only from theCallistephus chinensisNees. However, the mechanism of action of CA on alcoholic liver disease remains unclear. In this study, alcoholic liver mice were fed with 20 and 40 mg/kg CA, respectively, for 11 days. This study showed that CA improved hepatic steatosis and oxidative stress associated with alcohol consumption. CA alleviated liver inflammation by inhibiting the TLR4/MYD88/NF-κB pathway, ameliorating gut imbalance by restoring the abundance ofAkkermansia, and restoring short-chain fatty acids in the gut. Transcriptome analysis revealed that CA primarily affects genes involved in lipid metabolism and inflammation. In vitro, by adding inhibitors of TLR4 (TAK-242) and AMPK (Dorsomorphin), it was confirmed that CA alleviates ALD by inhibiting TLR4 and activating AMPK. This study is the first to demonstrate that CA protects against alcoholic liver disease through the regulation of the gut flora and modulation of the AMPK/NF-κB pathway. In conclusion, CA can effectively improve alcoholic liver disease and can be used as an effective candidate drug with liver-protective effects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Shuai Mao,Lei Wang,Peipei Chen,Yong Lan,Rui Guo,Minzhou Zhang
Our previous works have shown that tanshinone IIA inhibited maladaptive extracellular matrix remodeling in cardiac fibroblasts implicating its potential role in treating of pathologic cardiac remodeling. However, the intrinsically poor solubility and bioavailability of tanshinone IIA hindered its clinical application. Here we develop monomethoxy-poly (ethylene glycol)-poly (lactic acid)-D-α-Tocopheryl polyethylene glycol 1000 succinate (mPEG-PLA-TPGS) nanoparticle incorporating tanshinone IIA (tanshinone IIA-NPs) and study its efficacy in post-infarction left ventricular (LV) remodeling. Male C57BL/6 mice underwent left coronary artery ligation followed by subsequent intravenously injected tanshinone IIA-NPs therapy for 5 consecutive days. Treatment with tanshinone IIA-NP improved cardiac function, limited infarct expansion, and prevented left ventricle dilation at 4 weeks post-MI. Furthermore, cardiomyocytes inflammation, apoptosis and myocardial fibrosis were significantly attenuated in tanshinone IIA-NP treated mice. These effects also correlated with inhibition of IκB protein phosphorylation and NF-κB activation, leading to suppression of proinflammatory cytokine expression. Together, these results demonstrate tanshinone IIA-NP attenuated adverse cardiac remodeling and dysfunction mediated through prevention of IκB phosphorylation and NF-κB activation. Tanshinone IIA-NP is a novel approach to treat myocardial IR injury in patients with MI.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 3
·1473-1483
·
IF 2.784
Jun Fu,Luhua Yu,Jie Luo,Rui Huo,Bing Zhu
The purpose of the present study was to analyze the association between paeonol and the known genes related to gastric cancer (GC) using bioinformatics methods, and to investigate the role of paeonol in the potential impact on the nuclear factor‑κB (NF‑κB) signaling pathway, in order to provide a theoretical basis for further elucidating the effect of paeonol on cancer cells. Cell viability, morphology and apoptosis were detected using an MTT assay, an inverted microscope, and flow cytometry, respectively. The correlation between drugs and genes was analyzed using the Search Tool for Interactions of Chemicals (STITCH) gene‑drug interaction network. The expression levels of related mRNA and proteins were determined using reverse transcription‑quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assay. The changes in protein expression were examined using western blot analysis. The correlation network between target genes directly affected by paeonol and known GC genes was determined by analyzing the association between the compounds and genes recorded in the STITCH database. The GC‑related epidermal growth factor receptor 2 (ERBB2) gene was at the core position of the paeonol interaction network and may be an important potential target gene for the effect of paeonol on cancer cells. The effect of paeonol on the viability of the SGC‑7901 GC cell line was detected using an MTT assay, which showed that the inhibitory effect occurred in a time‑ and dose‑dependent manner. The observations of cell morphology demonstrated that the cells were floating, abnormal in shape, had unclear boundaries and were sparse in arrangement following paeonol treatment. Flow cytometry indicated that paeonol significantly accelerated the apoptotic rate of the SGC‑7901 GC cells. The examination of clinical samples suggested that ERBB2 was expressed at a high level in GC samples, and was significantly downregulated following the addition of paeonol. The western blot analysis revealed that downregulating ERBB2 affected the activation of the NF‑κB signaling pathway, thereby upregulating the pro‑apoptotic factor B‑cell lymphoma‑associated X protein. Taken together, paeonol significantly downregulated ERBB2 and inhibited the activation of the NF‑κB signaling pathway, thereby inhibiting the proliferation of SGC‑7901 cells and inducing apoptosis.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）