AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·Vol. 53
·期 03
·909-930
·
IF 5.5
Ke Li,Ya-Jun Wang,Kun Wei,Wen-Lin Li,Yong-Bo Liu,Jun-Nan Hu,Wen-Guang Chang,Wen-Xuan Zhang,Long Chen,Wei Li
Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng ( Panax ginseng . C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1 β ) . In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro , suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.
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高影响因子
MICROVASCULAR RESEARCH
·
2025
·
IF 2.7
Xiao Xu,Xiaohu Ge,Hongbo Ci,Maitiseyiti Abulaihaiti,JianPing Yang,YangYang Li,Feng Zhu
Background Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO. Methods Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Results Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats. Conclusion PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.
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iScience
·
2025
·
IF 4.1
Qian Wang,Jie Chen,Huini Chen,Dongning Liang,Hong Zhou,Juanjuan Chen,Yuan Gui,Fang Yao,Yudan Chen,Xi Zeng,Yaxiang Ma,Dong Zhou,Haiyan Fu
Cisplatin is a commonly used chemotherapy agent for treating various solid tumors, but its clinical application is limited by nephrotoxicity. While the potential for cisplatin to cause chronic kidney disease (CKD) following repeated administration has been underexplored, effective therapeutic strategies for cisplatin-induced CKD are lacking. We found that cisplatin-induced CKD is characterized by renal dysfunction and inflammation, along with intestinal barrier impairment. 16S rRNA and metabolomics revealed that cisplatin disrupts the gut microbiome and raises levels of tryptophan metabolites- Indole-3-propionic acid (IPA). Notably, oral administration of IPA reproduced similar harmful effects in cisplatin-induced CKD. Integrated analyses of the microbiome, metabolomics, Raman spectroscopy and DESI-MSI indicated that IPA supplementation exacerbates the production of uremic toxins linked to tryptophan metabolism and promotes the growth of pathogenic bacteria. Our findings demonstrates that IPA exacerbates renal inflammation and fibrosis by regulating AHR/NF-κB signaling pathways, altering intestinal microbiome composition, and disrupting tryptophan metabolism.
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Redox Biology
·
2025
·
IF 11.9
Ding Liu,Yuanzhi Ye,Zirong Lan,An Chen,Xingchen Zhou,Zhenhao Li,Xin Wen,Jisheng Xiao,Fan Ouyang,Jianyun Yan
Vascular calcification, prevalent in patients with chronic kidney disease, atherosclerosis, and diabetes, is strongly associated with elevated cardiovascular morbidity and mortality, highlighting the urgent need for effective treatments. Oxidative stress is a key contributor to the progression of vascular calcification. Nanozymes, nanomaterials with enzyme-like catalytic properties, exhibit strong reactive oxygen species (ROS) scavenging abilities and good biocompatibility, making them promising therapeutic candidates. This study aims to investigate whether polyvinylpyrrolidone (PVP)-functionalized ultrasmall Cu 2-x Se nanoparticles (CSP NPs) act as nanozymes for treating vascular calcification. In vitro , CSP NPs significantly inhibit calcification of rat and human vascular smooth muscle cells (VSMCs) and reduce the expression of osteogenic markers Runx2 and BMP2. Moreover, CSP NPs alleviate calcification of rat and human arterial rings. In a mouse model, CSP NPs localize to certain areas, such as the aortic arch and abdominal aortas, and are safely metabolized by the liver and kidneys without organ toxicity. Further analyses confirm that CSP NPs inhibit mouse and chronic kidney disease (CKD) rat aortic calcification. Mechanistically, CSP NPs inhibit oxidative stress and mitochondrial dysfunction. Additionally, CSP NPs decrease the expression of NF-κB and NLRP3, thus reducing the levels of inflammatory cytokines IL-1β and IL-6. CSP NPs suppress NLRP3 activator-induced calcification in VSMCs and arterial rings. This study provides the first evidence that CSP NPs alleviate vascular calcification by inhibiting oxidative stress and NF-κB/NLRP3-mediated inflammation, suggesting a promising therapeutic approach.
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Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1349
·
IF 7.5
Zhu Ganggui,Li Qiaxuan,Yao Qifeng,Zhao Jin,Ding Shuo,Mai Shixiong,Yue Bingqin,Chen Jingyu,Huang Man
Background Lung ischemia-reperfusion injury (LIRI) is associated with a variety of postoperative complications and affects patient prognosis. β-Nicotinamide mononucleotide (NMN) has attracted much attention due to its potential role in cellular energy metabolism and antioxidant properties. Exploring the mitigating role of NMN in ischemia-reperfusion injury after lung transplantation is crucial for improving lung transplantation success and patient quality of life. Methods A LIRI model was established using the mouse left lung portal clamp method, and the cold ischemia-reperfusion (CI/R) model with BEAS-2B cells in vitro was used to simulate the lung transplantation environment. The protective effect of NMN against lung ischemia-reperfusion injury was analyzed by histopathology, ELISA, immunofluorescence, Western blot and RT-PCR. Combined multi-omics profiling were used to study the mechanisms by which NMN attenuated lung ischemia-reperfusion injury. Results NMN significantly attenuated ischemia-reperfusion-induced structural abnormalities, pulmonary edema, inflammatory infiltration and oxidative stress injury in mouse lung tissue. Similarly, NMN attenuated CI/R-induced oxidative stress and inflammatory responses in BEAS-2B cells. Based on multi-omics analysis, we found that NMN ameliorated the apoptosis after ischemia/reperfusion through down-regulation of cleaved Caspase 3, BAX and up-regulation of BCL-2. Moreover, NMN also affected mitochondrial metabolic processes, including promoting mitochondrial oxidative phosphorylation, increasing ATP synthesis, enhancing mitochondrial complex activity, decreasing ROS generation, slowing down the decrease of mitochondrial membrane potential, and inhibiting the opening of the mitochondrial membrane permeability transition pore. Mechanistically, we found that NMN attenuates inflammation and oxidative damage through activation of the SIRT1 and NF-κB signaling pathways, and that SIRT1-specific inhibition of EX527 reversed these protective effects of NMN against inflammation and oxidative damage in vivo and in vitro. Conclusion NMN has a protective effect on inflammation and oxidative damage induced by ischemia-reperfusion injury after lung transplantation, and the SIRT1/NF-κB pathway may be involved in one of the mechanisms of the protective effect.
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Biology-Basel
·
2025
·Vol. 14
·期 11
·1573
·
IF 3.5
Shize Zhang,Tian Cheng,Yuang Chen,Mengqin Wang,Guangji Wang,Jiye Aa
Based on emerging evidence linking vitamin homeostasis to inflammatory bowel disease, this study investigated the causal role and therapeutic potential of folate in ulcerative colitis. By employing Mendelian randomization and experimental models, we demonstrated that folate supplementation markedly attenuated colitis severity, suppressed inflammatory responses, and restored the structure and function of the epithelial barrier. Mechanistically, folate acts through inhibition of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis, leading to improved barrier integrity and reduced mucosal inflammation. These findings establish folate not only as a protective nutrient but also as a potential therapeutic agent, supporting its use in clinical nutritional strategies for ulcerative colitis management. Vitamin homeostasis plays a critical role in inflammatory bowel disease management, yet the protective mechanisms and clinical utility of specific vitamins remain incompletely characterized. Within this context, a two-sample Mendelian randomization analysis leveraging genetic instruments for measuring circulating vitamin levels identified folate as a protective factor against ulcerative colitis (UC). To validate these findings, a DSS-induced colitis model was established with serial serum folate measurements. Therapeutic folate supplements were subsequently administered, followed by a comprehensive evaluation of epithelial barrier modulation through in vivo and recombinant TNF-α/IFN-γ-induced in vitro models. This included assessment of junctional proteins, ultrastructural analysis by transmission electron microscopy, and functional quantification of barrier integrity using transepithelial electrical resistance with paracellular permeability assays in epithelial monolayers. Molecular mechanisms were investigated through RNA sequencing complemented by immunoblot validation of key pathway components. The results demonstrated decreased serum folate levels in DSS-induced colitis mice, whereas folate supplementation ameliorated disease severity and attenuated intestinal inflammation and histopathological damage. Crucially, folate restored epithelial barrier structural integrity and function both in vivo and in vitro. Mechanistically, folate mediated barrier restoration through suppression of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis. Collectively, the results of this study provide mechanistic insights that support the use of folate as an active therapeutic molecule in patients with UC.
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高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Jiong Wang,Chenchen Qian,Yue Chen,Tianyang Jin,Yongsheng Jiang,Lijiang Huang,Xinyan Fu,Dong Yang,Leiming Jin,Bo Jin,Yi Wang
ABSTRACT Background Hyperglycemic induced cardiac hypertrophy and cardiac inflammation are important pathological processes in diabetic cardiomyopathy. β-elemene (Ele) is a natural compound extracted from Curcuma Rhizoma and has anti-tumor effects. It also has therapeutic effects in some inflammatory diseases. However, the therapeutic effect of Ele on diabetic cardiomyopathy is not clear. The purpose of this study was to evaluate the effect of Ele on hyperglycemia-caused cardiac remodeling and heart failure. Methods C57BL/6 mice were intraperitoneally injected with streptozotocin to induce DCM, and Ele was administered intragastric after 8 weeks to investigate the effect of Ele. RNA sequencing of cardiac tissue was performed to investigate the mechanism. Results Ele markedly inhibited cardiac inflammation, fibrosis and hypertrophy in diabetic mice, as well as in high glucose-induced H9c2 cells. RNA sequencing showed that cardioprotective effect of Ele involved the JAK/STAT3-NF-κB signaling pathway. Ele alleviated heart and cardiomyocyte inflammation in mice by blocking diabetes-induced JAK2 and STAT3 phosphorylation and NF-κB activation. Conclusions The study found that Ele preserved the hearts of diabetic mice by inhibiting JAK/STAT3 and NF-κB mediated inflammatory responses, suggesting that Ele is an effective therapy for DCM.
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高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Yingying Cai,Jiali Hu,Mingjie He
Materials and Methods LOAD rats and A β microglia were constructed by using A β 1-40 and IBO mixture. The effect of KL-FGF23-VD axis on LOAD was investigated by transfecting overexpressing and interfering with KL gene adenovirus, and IKK-16 was added to A β microglia to explore the effect of KL-FGF23-VD axis on regulation of IKK/NF- κ B signaling pathway. Results The results showed that, in KL-OE group, FGF23 was decreased in the hippocampus of LOAD rats compared with control and KL-si, and the trend was opposite in the KL-si group. The KL-FGF23-VD axis can alleviate inflammatory response, reduce the deposition of A β , and inhibit activation of the NF- κ B pathway and neuron apoptosis in brain tissue of LOAD rats. In A β microglia, the expression of KL-FGF23-VD axis was consistent with animal experiments. The KL-FGF23-VD axis can inhibit the expression of A β microglia inflammatory factors and the activation of microglia and NF- κ B pathway. Meanwhile, IKK expression was decreased in KL-OE group compared with KL-si and Control. In the IKK-16 addition group, the ability of KL-FGF23-VD axis to inhibit the activation of microglia and NF- κ B pathway was enhanced. Conclusions These findings suggest a potential role of the KL-FGF23-VD axis in AD treatment by regulating the IKK/NF- κ B pathway.
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高影响因子
Heliyon
·
2023
·Vol. 9
·期 11
·e21871
·
IF 4
Tianhang Chen,Haixia Du,Huifen Zhou,Yu He,Jiehong Yang,Chang Li,Chenxing Wei,Daojun Yu,Haitong Wan
Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii ( A. baumannii ) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii , which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.
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高影响因子
IONICS
·
2022
·Vol. 28
·期 8
·3935-3944
·
IF 2.961
Wu Yanxia,Chen Xiangping,Su Lirong,Wang Qingtao,Ren Shufang
Increasing active sites by constructing a heterostructure is a very effective method to improve the electrocatalytic performance. In this work, we synthesized a three-dimensional self-supporting Ni 2 P-Ni 12 P 5 /NF heterostructure supported on nickel foams by hydrothermal reaction and low-temperature phosphorization, used as an efficient hydrogen evolution reaction (HER) electrocatalyst. The structure, composition, morphology, and HER performance of the catalyst were characterized by XRD, XPS, SEM, TEM, and electrochemical workstation. The experimental results show that the Ni 2 P-Ni 12 P 5 /NF heterostructure demonstrates better HER catalytic activity in 0.5 M H 2 SO 4 , only requiring an overpotential of 124 mV at 10 mA cm −2 with a Tafel slope of 84.1 mV dec −1 and displaying good long-term stability. The high activity and stability of the as-synthesized Ni 2 P-Ni 12 P 5 /NF catalyst in HER are mainly due to the synergy between Ni 2 P-Ni 12 P 5 with a unique heterostructure and nickel foam conductive substrate with a three-dimensional porous structure, which is beneficial to increase the electrocatalytic active area and thus provide more active sites.
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Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2024
·Vol. 34
·期 3
·637-646
·
IF 1.4
Guo Liyang,Xue Xuexue,Zhou Yang,Chen Chunli,Sheng Zunlai
Diarrhea continues to be a major public health problem and is thought to be the cause of 525,000 child fatalities annually. Studies have shown that Macleaya cordata (Willd.) R.Br., Papaveraceae, has a good therapeutic effect on diarrhea due to its action on ion channels. However, its antidiarrheal mechanisms and key targets are not supported by scientific research. This study aimed to identify the mechanisms of action and targets of the primary active antidiarrheal compounds of M. cordata . We used network pharmacology and molecular docking to identify the antidiarrheal mechanisms and the key targets of M. cordata and its main chemical constituents. Subsequently, the experiments performed with dihydrosanguinarine (25, 50, and 100 mg/kg), which included the evaluation of the inhibitory potential of the epidermal growth factor receptor in osimertinib-induced diarrhea, real-time quantitative PCR, and western blotting, were performed for further verification of its mechanism of action. The findings revealed that of all the genes, tyrosine-protein kinase Lck, receptor tyrosine-protein kinase Erbb2, and epidermal growth factor receptor had the highest capacity of action, and the NF-kappa B and the calcium signaling pathways may play essential roles in M. cordata against diarrhea. Dihydrosanguinarine is the most active ingredient, and it significantly inhibits the increase in incidence and decreased the fecal water content of osimertinib-induced diarrhea. Western blot and qRT-PCR showed that dihydrosanguinarine works as an antidiarrheal agent by upregulating the expression of the core target epidermal growth factor receptor, affecting the NF-kappa B and the calcium ion signaling pathways, downregulating the expression of calcium-activated chloride channel and NK-kappa B P-65. Graphical
研究领域:
药理学
·
分子生物学
·
中药研究
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Journal of Materials Chemistry A
·
2026
·
IF 9.5
Wensong Wang,Ying Tian,Xiuwen Cao,Xiang Liu,Shizhe Cao,Deheng Chen,Weizi Jiang,Mingtao Li,Weiwei Lin,Xun Sun,Shenjie Li,Yanyan Chen
The urea oxidation reaction (UOR), with its low theoretical potential, can replace the oxygen evolution reaction (OER) at the anode in water electrolysis, thereby reducing the thermodynamic barrier of electrochemical water splitting. However, in practical UOR electrocatalysts, the adsorption competition between urea and OH⁻ constitutes a kinetic bottleneck. Conventional catalysts lack dynamic regulation means, which ultimately leads to the occurrence of competitive adsorption. In this study, we constructed a CuxS/FeS/NF heterojunction electrocatalyst via hydrothermal methods, achieving highly efficient catalysis for UOR-assisted overall water splitting. The heterojunction features an open and disordered hierarchical porous structure, significantly increasing the specific surface area and active site density (with a double-layer capacitance of 8.33 mF cm -2 ). More importantly, the reversible Cu + /Cu 2+ valence cycling on the heterojunction surface dynamically modulates urea adsorption sites, addressing the issue of OH -occupying active centers and accelerating reaction kinetics (Tafel slope as low as 26.28 mV dec -1 ). In-situ Raman tests confirm that Cu 2+ forms strong coordination with -NH₂ via empty orbitals, while Cu + weakens the adsorption of OH⁻ through high electron density; the two species synergistically accelerate the reaction kinetics. Electrochemical tests reveal that in the UOR||HER system, CuxS/FeS/NF only requires a potential of 1.35 V vs. RHE to achieve a current density of 10 mA cm -2 , while for the HER, it needs merely 78 mV to reach the same current density. When applied to UOR-assisted overall water splitting in a 1 M KOH + 0.33 M urea electrolyte, the system requires only 1.440 V vs. RHE cell voltage to deliver a current density of 50 mA cm -2 and maintains stable operation for 60 hours, with a urea degradation rate of 66.4% after 20 hours. This work, through the dynamic regulation mechanism of copper valence cycling, provides a novel approach for designing UOR catalysts with both high activity and stability, holding significant application potential in low-energy hydrogen production and wastewater treatment.
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