CHEMICAL ENGINEERING JOURNAL
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2026
·
IF 12.5
Yana Ma,Wen Luo,Weijia Zhu,Zhichao Deng,Shijun Xu,Hang Yuan,Wei-jun Fan,Quanjun Yao,Wei Yao,Ho-Young Song,Mingzhen Zhang,Jizhao Wang,Hongtao Hu
Oxidative stress, resulting from excessive reactive oxygen species (ROS), is critically involved in the development and progression of inflammatory diseases such as inflammatory bowel disease. Therefore, targeting ROS for the treatment of inflammation holds great potential, and the underlying mechanism is of great significance for clinical medication. In this work, carbon dots (C-dots) based on chrysanthemum as carbon source were obtained through a hydrothermal method. The as-prepared C-dots exhibited favorable ROS scavenging capacity and biocompatibility. The ROS level and the oxidative damage were reversed, the expression of proinflammatory factors was reduced, and the disrupted barrier was recovered by chrysanthemum-derived C-dots in the cellular inflammatory model. The anti-inflammatory effects were also validated in mice colitis model. Mechanistically, the chrysanthemum-derived C-dots regulated the Keap1/Nrf2 antioxidant signaling and inhibited the NF-κB/NLRP3 inflammasome-mediated inflammatory signaling, thereby restoring redox homeostasis and modulating the inflammatory microenvironment. Collectively, the C-dots from chrysanthemum with preferable biocompatibility hold a bright prospect in inflammation resolution through remodeling redox and inflammatory microenvironment.
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BIOCHEMICAL PHARMACOLOGY
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2026
·
IF 6.5
Xia Wu,Chun-Feng Liu
Septic cardiomyopathy (SCM) is a prevalent complication among septic patients, accompanied by high mortality. Estrogen‐related receptor alpha (ERRα), a transcription factor, is implicated in various cardiovascular diseases. Nonetheless, its role in SCM remains unclear. Here, the cecum ligation and puncture (CLP) procedure was used to construct a mouse sepsis model. We found that the ERRα expression was downregulated in septic hearts. Adeno-associated virus-9 (AAV-9)-mediated cardiomyocyte-specific ERRα overexpression improved the survival rate of septic mice. Additionally, ERRα overexpression ameliorated CLP-induced cardiac dysfunction and myocardial pathological damage. In vitro , HL-1 mouse cardiomyocytes were transduced with an ERRα overexpression adenovirus before LPS stimulation. The results demonstrated that ERRα overexpression mitigated LPS-induced inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-18) and apoptosis (Bax, cleaved caspase-3/9) in HL-1 cells. Mechanistically, ERRα inhibited the NF-κB/NLRP3 inflammasome activation in septic hearts and LPS-stimulated HL-1 cells. Furthermore, we overlapped the differentially expressed genes of septic hearts (GSE125042) and ERRα KO hearts (GSE7196) to identify the downstream target genes. Meteorin like, glial cell differentiation regulator (METRNL) was identified as the target gene of ERRα. Notably, ERRα bound to the METRNL promoter and upregulated its activity, which was confirmed via dual-luciferase reporter assay, ChIP-qPCR, and oligonucleotide pull-down assay. Knockdown of METRNL prevented the effects of ERRα overexpression on the apoptosis and inflammatory response of cardiomyocytes induced by LPS. Our findings underscore the role of ERRα in mitigating myocardial injury in SCM, indicating its potential as a new therapeutic approach.
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Metabolites
·
2026
·Vol. 16
·期 5
·340
·
IF 4.5
Xue Zhang,Wei Liu,Zhijing Fu,Zhuoling Chen,Qixin Chen,Yanan Shen,Yukai Jin,Dengfeng Xu,Yin Wang,Xuefeng Qu,Yangjunna Zhang
Background: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in diabetic cardiomyopathy (DCM) induced by Type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood.Methods: A T2DM mouse model was established via a high-fat diet and low-dose STZ. We investigated the cardioprotective effects of 12-week oral PQQ administration, assessing fasting blood glucose, oral glucose tolerance, cardiac function, myocardial histopathology, blood biochemistry, mitophagy, and NLRP3 inflammasome activation. In vitro experiments using AC16 cardiomyocytes exposed to palmitic acid and high glucose were also conducted.Results: Results showed PQQ significantly improved cardiac function, attenuated remodeling, and reduced proinflammatory cytokines in mice with T2DM, regulated key mitophagy-related proteins (Parkin, Beclin-1, LC3B-II, p62), and downregulated NLRP3 inflammasome pathway components (Caspase-1, NLRP3, IL-1β, IL-18). In vitro experiments demonstrated that PQQ reduced reactive oxygen species (ROS) production, improved mitochondrial membrane potential, promoted mitophagy, and inhibited NLRP3 inflammasome-mediated pyroptosis.Conclusions: PQQ alleviates DCM in mice with T2DM by improving mitochondrial quality control, promoting mitophagy, and subsequently inhibiting NLRP3 inflammasome-mediated pyroptosis, highlighting its potential as a promising therapeutic agent for T2DM-associated cardiomyopathy.
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Food & Function
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2022
·Vol. 13
·期 7
·3946-3956
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IF 6.317
Zhe Wang,Chunhai Li,Xi He,Kang Xu,Zhipeng Xue,Ting Wang,Zhenshang Xu,Xinli Liu
The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.
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Oxidative Medicine and Cellular Longevity
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2022
·
IF 7.31
Xinye Wang,Ran Huo,Zhongjie Liang,Congcong Xu,Tingting Chen,Jingjing Lin,Luyao Li,Wei Lin,Bingting Pan,Xiaoqin Fu,Shangqin Chen
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly found in premature infants. Excessive inflammation and oxidative stress contribute to BPD occurrence and development. Simvastatin, as an inhibitor of HMG-CoA reductase, has been reported to have antioxidative and anti-inflammatory effects. However, its effect and possible mechanisms in hyperoxia-induced lung injury are rarely reported. In this study, in vivo and in vitro experiments were conducted to investigate whether simvastatin could ameliorate hyperoxia-induced lung injury and explore its potential mechanism. For the in vivo study, simvastatin could improve alveolar development after hyperoxic lung injury and reduce hyperoxic stress and inflammation. The in vitro study revealed that simvastatin can reduce inflammation in A549 cells after high-oxygen exposure. Simvastatin suppressed NLRP3 inflammasome activation and played anti-inflammatory and antioxidant roles by increasing KLF2 (Krüppel-like factor 2) expression. In vitro experiments also revealed that these effects of simvastatin were partially reversed by KLF2 shRNA, indicating that KLF2 was involved in simvastatin effects. In summary, our findings indicate that simvastatin could downregulate NLRP3 inflammasome activation and attenuate lung injury in hyperoxia-induced bronchopulmonary dysplasia via KLF2-mediated mechanism.
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Frontiers in Pharmacology
·
2022
·
IF 5.988
Chuyao Liao,Di Wang,Siyuan Qin,Ying Zhang,Jie Chen,Ruijie Xu,Fengguo Xu,Pei Zhang
Irinotecan (CPT-11) in combination with 5-fluorouracil and leucovorin is a first-line chemotherapy regimen for the treatment of colorectal cancer; however, its clinical application is limited by the dose-limiting gastrointestinal toxicity of colitis. In our previous studies, several bile acids (BAs) were found significantly elevated in the colon of the CPT-11-induced rat colitis model. On the other hand, NLRP3 inflammasome has been reported to play important roles in mediating colitis. Interestingly, BA was stated to activate the NLRP3 inflammasome in some studies, while in some other reports, it showed an inhibitory effect. We assumed that the inflammatory status in different circumstances might have contributed to the controversial findings. In this study, we first discovered, under non-inflammatory conditions, that supplementing BA could activate the NLRP3 inflammasome in THP-1-differentiated macrophages and promote inflammation. In lipopolysaccharide (LPS)-induced inflammatory macrophages, however, BA inhibited the NLRP3 inflammasome and reduced inflammation. Further experiments demonstrated that Takeda G protein-coupled receptor 5 (TGR5) is essential in mediating the inhibitory effect of BA, while phospho-SP1 (p-SP1) is key to the activation. Furthermore, we applied the above findings to ameliorate CPT-11-caused colitis in rats by inhibiting SP1 with mithramycin A (MitA) or activating TGR5 using oleanolic acid (OA). Our findings may shed light on the discovery of effective interventions for reducing dose-limiting chemotherapy-induced colitis.
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Food & Function
·
2020
·Vol. 11
·期 6
·5156-5165
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IF 4.171
Yu-Sheng Shi,Xiao-Xing Li,Hao-Tian Li,Yan Zhang
Liver fibrosis is a histological change that often occurs due to hepatic stellate cell (HSC) activation and excessive formation of an extracellular matrix in the liver. Pelargonidin (PEL) is a natural anthocyanidin existing in blueberries, berries, strawberries, and red radishes and has been demonstrated to possess health beneficial effects. Herein, we investigated the effect of PEL on liver fibrosis induced by CCl4 and hepatic stellate cells induced by transforming growth factor-β (TGF-β). We found that PEL administration prevented liver injury and liver fibrosis induced by CCl4 in a dose-dependent manner. Further data revealed that PEL increased liver nuclear factor E2-related factor 2 (Nrf2) and reduced liver oxidative stress and the expression levels of NLRP3, caspase-1 and IL-1β. In TGF-β-challenged HSCs (LX-2 cells), PEL effectively inhibited the LX-2 cell activation. In addition, the anti-fibrosis effects of PEL in LX-2 cells were abolished by Nrf2 knockdown. In summary, our study demonstrated that PEL ameliorated CCl4-induced liver fibrosis and HSC activation induced by TGF-β. The possible molecular mechanisms of PEL in liver fibrosis may be attributed to its suppression of ROS-NLRP3-IL-1β signaling by Nrf2 activation.
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Food & Function
·
2020
·Vol. 11
·期 9
·7925-7934
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IF 4.171
Yi-Chao Du,Li Lai,Hao Zhang,Fu-Rui Zhong,Huan-Li Cheng,Bao-Lin Qian,Peng Tan,Xian-Ming Xia,Wen-Guang Fu
Acetaminophen (APAP) is one of the safest and most effective over-the-counter (OTC) analgesics and antipyretics, but excessive doses of APAP will induce hepatotoxicity with high morbidity and mortality worldwide. Kaempferol (KA), a flavonoid compound derived from the medicinal and edible plant of Penthorum chinense Pursh, has been reported to exert a profound anti-inflammatory and antioxidant activity. In this study, we explored the protective effect and novel mechanism of KA against APAP-induced hepatotoxicity. The results revealed that KA pretreatment significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), relieved hepatocellular damage and apoptosis, attenuated the exhaustion of glutathione (GSH) and accumulation of malondialdehyde (MDA), increased the expression of antioxidative enzymes (e.g., heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1)), and thus restrained APAP-induced oxidative damage in the liver. KA suppressed the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Moreover, KA remarkably inhibited high-mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) expression as well as nuclear factor kappa-B (NF-κB) activation for liver protection against APAP-induced inflammatory responses and apoptosis. Taken together, our findings suggested that KA could effectively protect hepatocytes from APAP hepatotoxicity through the up-regulation of HO-1 and NQO1 expression, the down-regulation of NLRP3 expression, and the inhibition of the HMGB1/TLR4/NF-κB signaling pathway.
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International Journal of Environmental Research and Public Health
·
2019
·Vol. 17
·期 1
·138
·
IF 2.468
Chang Liu,Yaohui Zhu,Zhenxiang Lu,Weina Guo,Bayaer Tumen,Yalan He,Chao Chen,Shanshan Hu,Kangzhi Xu,Yan Wang,Lei Li,Shenghe Li
Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.Keywords:Cadmium;acute liver injury;Nrf2;NLRP3;NF-κB;MAPKs
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ENVIRONMENTAL POLLUTION
·
2022
·
IF 9.988
Yuanyuan Zhou,Hanyu Liao,Shanshan Yin,Pengqiao Wang,Xiaoqing Ye,Jianyun Zhang
Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocytes is still limited. In this study, nine most frequently detected OPEs were selected and divided into three subgroups (aryl-, halogenated- and alkyl-OPEs) based on their substituents. The cytotoxicity, apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation induced by OPEs were evaluated in human hepatocellular carcinomas HepG2 cells. All OPEs induced apoptosis likely through a caspase-dependent apoptotic pathway. The activities of anti-oxidative enzyme SOD and CAT exhibited sensitive responses after OPEs treatment for 6 h. The OPEs induced ROS overproduction, DNA damage, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation varied among aryl-, halogenated- and alkyl-OPEs. Halogenated- and alkyl- OPEs induced overproduction of ROS and DNA damage, and elevated ER stress and NLRP3 inflammasome activation are observed aryl-OPEs induced cytotoxicity.
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BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Hui Li,Hengli Luo,Xin Zhang,Jianchun Luo,Chenglin Zhan,Xiaofang Gong,Minghua Liu,Xiangfeng Chen,Ge Zhao
Rhoifolin alleviated pathological and histological changes in DNCB-induced Balb/c mice with AD-like responses. • Rhoifolin suppressed pro-inflammatory chemokine and cytokine production in TNF-α/IFN-γ-stimulated HaCaT cells. • Rhoifolin regulated skin barrier function and inflammation via PPARα-mediated NF-κB/NLRP3 pyroptosis signaling. Rhoifolin (ROF), a naturally occurring flavonoid glycoside, has been documented to possess a broad spectrum of biological properties, including anticancer, antioxidant, neuroprotective, hepatoprotective, anti-inflammatory, and antiviral activities. Atopic dermatitis (AD) is a persistent, recurring inflammatory skin illness that frequently greatly compromises the patients' quality of life. Nevertheless, the role of ROF in AD pathogenesis and the associated molecular events have yet to be elucidated. Our findings revealed that ROF administration substantially ameliorated the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like phenotypes, as reflected by decreased mast cell accumulation, reduced CD4 + and CD8 + T cells infiltration within lesional skin, lowered serum immunoglobulin E (IgE) concentrations, attenuated epidermal and dermal thickening, suppressed histamine liberation and pruritic episodes, improved SCORAD indices, concomitant restoration of skin barrier protein expression, and curtailed the production of multiple inflammatory factors. Mechanistic investigations, integrating network pharmacology forecasts, transcriptomic profiling, and pharmacological blockade experiments with specific antagonists, further confirmed that the anti-inflammatory action of ROF operates through the PPARα-regulated NF-κB/NLRP3 signaling cascade. Collectively, these observations demonstrate that ROF exerts favorable inhibitory effects against AD-like inflammation both in vivo and in vitro , underscoring its potential as a viable therapeutic option for managing AD and other inflammatory cutaneous disorders. Download: Download high-res image (81KB) Download: Download full-size image
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AQUACULTURE
·
2023
·
IF 4.5
Enzhuang Pan,Huimiao Feng,Zuwang Yang,Yue Xin,Xiaomeng Ji,Kaixin Ping,Yong Sun,Jingquan Dong
As a widely used fungicide at present, difenoconazole can enter the aquatic ecosystem and cause adverse effects on freshwater carp culture. The spleen, an important immune organ of carp, is vulnerable to damage by environmental toxins. Studies have shown that the inflammatory response is an important mechanism of immunotoxicity of difenoconazole. Whereas quercetin has anti-inflammatory pharmacological activity, the role and mechanism of quercetin in difenoconazole-induced inflammatory damage in the spleen of carp is unknown. In this study, we developed a model for carp with quercetin added to the diet and exposed to environmentally relevant concentrations of difenoconazole. We found that quercetin protects against inflammatory damage in the splenic tissue of carp through histopathological observations. We found that quercetin alleviated ROS enrichment and disruption of redox homeostasis (dynamic balance of GSH, T-AOC, CAT, and MDA) in the spleen tissue of carp by fluorescence assay and biochemical assay. We found that quercetin was able to inhibit the activation of the NF-κB signaling pathway (elevated p-NF-κB p65 expression level) and NLRP3 inflammasome pathway (NLRP3/ASC/caspase-1) in carp spleen tissue induced by difenoconazole by immunohistochemistry and qPCR analysis. In conclusion, this study confirms that the addition of quercetin as a supplement to the diets of freshwater cultured carp is effective against the spleen toxicity induced by difenoconazole. Mechanistically, quercetin may alleviate the difenoconazole-induced splenic inflammatory injury in carp by suppressing the excessive activation of ROS/NF-κB/NLRP3 inflammasome axis, providing new insights into the mechanism of quercetin alleviation of splenic inflammatory injury in carp.
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