FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Cuicui Duan,Mengchun Qin,Lifan Liu,Yixue Sun,Lin Cai,Lin Ma,Xiaolei Li,Fumin Ma,Dan Li
Proanthocyanidin (PC) is with antioxidant, anticancer and neuroprotective effects. Cow’s milk beta-lactoglobulin (β-Lg) is reported with higher immunoregulatory activity but lower antioxidative function. In this study, a β-Lg-PC complex was prepared, and the interaction and structural characterization of β-Lg-PC complex were investigated by fluorescence spectral analysis, infrared spectroscopy and molecular docking, etc. PC quenched the intrinsic fluorescence and changed the conformation of β-Lg. The optimal ratio of β-Lg and PC (10:3, w/w) was determined by measuring the particle size and ζ potential. Molecular docking results implied that the covalent binding among complex was mainly concentrated on the binding of PC to amino acid residue ILE 71. Moreover, the antioxidant effects and mechanism of β-Lg-PC complex were explored using LPS-induced oxidative stress model of RAW264.7 cells. The results showed that β-Lg-PC could alleviate oxidative stress by slowing down the LPS-induced decline in SOD enzyme activity, increase in ROS level, loss of mitochondrial membrane potential and increase in apoptosis in RAW264.7 cells.
研究领域:
食品科学
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生物化学
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免疫学
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2024
·Vol. 16
·期 10
·5385
·
IF 1.7
Hui Huang,Guanhua Wang,Dali Zeng
Objective: To investigate the protective effect of Peimine (PM) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the underlying mechanisms. Methods: KM mice were randomly divided into five groups: Control, LPS, Peimine low-dose (PM-L, 0.1 mg/kg), medium-dose (PM-M, 1 mg/kg), and high-dose (PM-H, 10 mg/kg) groups. Mice in the PM treatment groups received intraperitoneal injection of Peimine at different doses, while the mice in control and LPS groups received physiological saline. Afterwards, mice in the LPS and PM groups were subjected to intranasal instillation of LPS to establish the model of acute lung injury. The wet-to-dry (W/D) weight ratio of lung tissues was calculated, and H&E staining was performed to observe pathological changes in the lung tissues. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and MDA were measured using ELISA kits. Western blot was employed to assess the expression of NF-κB, IκBα, phospho-IκBα, Nrf2, HO-1, and SOD2 in lung tissues. RT-PCR quantified the mRNA levels of Nrf2 and its downstream genes HO-1 and NQO1. Additionally, RAW264.7 cells were treated with various drug concentrations for 24 hours followed by LPS exposure (100 ng/mL) for another 24 hours. Prior to treatment of RAW264.7 cells with PM and LPS, the ML385+PM group was pre-treated with ML385 (3 μM) for 4 hours. ELISA kits were used to measure TNF-α, IL-6, IL-1β, and MDA in cell supernatants, while ROS levels were determined using a ROS assay kit. Results: Compared with the model group, pretreatment with PM significantly reduced the lung tissue W/D weight ratio, ameliorated lung tissue pathological changes, and inhibited the secretion of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid. PM inhibited the LPS-induced elevation in lung tissue MDA levels, SOD2 consumption, and ROS levels. Furthermore, PM suppressed LPS-induced NF-κB activation and nuclear translocation, while significantly enhancing the protein expression of Nrf2 and HO-1 and increasing the mRNA levels of Nrf2 and its downstream genes, such as HO-1 and NQO1. In RAW264.7 cells, LPS induction led to elevated IL-1β, IL-6, TNF-α, MDA, and ROS levels, which were significantly suppressed by PM treatment. However, the antioxidative and anti-inflammatory effects of PM were effectively blocked by inhibiting the Nrf2 pathway. Conclusion: PM effectively ameliorates LPS-induced lung injury, primarily through inhibition of the NF-κB pathway, and activation of the Nrf2 pathway, alongside a reduction in the release of inflammatory factors.
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PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yong Zhang,Jingshu Tang,Yujun Zhou,Qiong Xiao,Qiuyu Chen,Hongyue Wang,Jiaqi Lan,Lei Wu,Ying Peng
Background: The pharmacological activity of dimethyl fumarate (DMF) in treating psoriasis and multiple sclerosis (MS) is not fully understood. DMF is hydrolysed to monomethyl fumarate (MMF) in vivo , which is believed to account for the therapeutic effects of DMF. However, previous studies have provided evidence that DMF also enters the circulation. Given that DMF is short-lived in the blood, whether DMF has a therapeutic impact is still unclear. Methods: Lipopolysaccharide (LPS)-mediated RAW264.7 cell activation was used as a model of inflammation to explore the anti-inflammatory effects of short-term DMF exposure in vitro . Whole blood LPS stimulation assay was applied to compare the anti-inflammatory effects of DMF and MMF in vivo . Griess assay was performed to examined nitrite release. The expression of pro-inflammatory cytokines and transcription factors were measured by quantitative PCR (qPCR), ELISA and Western blot. Depletion of intracellular glutathione (GSH) was evaluated by Ellman’s assay. Luciferase reporter assays were performed to evaluate DMF effects on Nrf2-ARE pathway activation, promoter activity of Nfkbiz and mRNA stability of Nfkbiz . Binding of STAT3 to the IκBζ promoter were examined using Chromatin immunoprecipitation (ChIP) assay. Results: Short-term exposure to DMF significantly inhibited the inflammatory response of RAW264.7 cells and suppressed LPS-induced IκBζ expression. Importantly, oral DMF but not oral MMF administration significantly inhibited IκBζ transcription in murine peripheral blood cells. We demonstrated that the expression of IκBζ is affected by the availability of intracellular GSH and regulated by the transcription factor Nrf2 and STAT3. DMF with strong electrophilicity can rapidly deplete intracellular GSH, activate the Nrf2-ARE pathway, and inhibit the binding of STAT3 to the IκBζ promoter, thereby suppressing IκBζ expression in macrophages. Conclusion: These results demonstrate the rapid anti-inflammatory effects of DMF in macrophages, providing evidence to support the direct anti-inflammatory activity of DMF.
研究领域:
药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2016
·
IF 3.418
Shuai Wang,Zewei Sun,Wenting Zhao,Zhen Wang,Mingjie Wu,Yanyun Pan,Hui Yan,Jianhua Zhu
CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-α and transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γ expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γ expression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-α secretion, partly through PPAR-γ upregulation.
研究领域:
免疫学
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细胞生物学
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炎症研究
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DOI
PubMed
高影响因子
Journal of Toxicologic Pathology
·
2022
·
IF 1.25
Wen-Ling Mou,Shi-Ru Chen,Zhen-Ting Wu,Li-Hua Hu,Ji-Ye Zhang,Hong-Jie Chang,Hang Zhou,Ying Liu
Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)–tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2–TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin–eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2–TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2–TNF-α signaling pathway.
研究领域:
分子生物学
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免疫学
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病理学
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药理学
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DOI
PubMed
高影响因子
Translational Psychiatry
·
2025
·
IF 6.2
He Dian,Guo Si-Yi,Yang Yi-Chun,Wang Hai-Yang,Zhang Yi,Mo Xiao-Long,Liu Lan-Xiang,Qin Zheng-Hong,Xie Peng
Our study investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) in neuroinflammation-associated depression-like behaviors. Using a lipopolysaccharide (LPS)-induced mouse model of depression, we found that NADPH significantly alleviated depressive-like behaviors, including reduced immobility time and increased sucrose preference. Mechanistic exploration revealed that NADPH suppressed microglial activation, downregulated pro-inflammatory cytokine expression (e.g., IL-1β, TNF-α, IFN-γ), and mitigated oxidative stress in the hippocampus, thereby ameliorating neuroinflammation. Furthermore, NADPH preserved myelin integrity, inhibited microglial phagocytosis of myelin and synapses, and preserved synaptic integrity. These findings provide experimental evidence supporting NADPH as a potential antidepressant agent and highlight its critical role in modulating neuroinflammation via dual suppression of cytokine release and microglial hyperactivation.
研究领域:
神经科学
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免疫精神病学
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分子生物学
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神经药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITION
·
2023
·
IF 4.2
Luyuan Kang,Jiaman Pang,Xiangyu Zhang,Yisi Liu,Yujun Wu,Junjun Wang,Dandan Han
Background L-arabinose has anti-inflammatory and metabolism-promoting properties, and macrophages participate in the alleviation of inflammation; however, the mechanism by which they contribute to the anti-inflammatory effects of L-arabinose is unknown. Objectives To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS). Methods Five-week-old male C57BL/6 mice were divided into 3 groups: a control and an LPS group that both received normal water supplementation, and an L-arabinose (ARA+LPS) group that received 5% L-arabinose supplementation. Mice in the LPS and ARA+LPS groups were intraperitoneally injected with LPS (10 mg/kg body weight), whereas the control group was intraperitoneally injected with the same volume of saline. Intestinal morphology, cytokines, tight junction proteins, macrophage phenotypes, and microbial communities were profiled at 6 h postinjection. Results L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and messenger RNA (mRNA) levels of TNF-α , IL-1β , interferon-γ ( IFN-γ ), and toll-like receptor-4 in jejunum and colon compared with those of the LPS group ( P < 0.05). The mRNA and protein levels of occludin and claudin-1 were significantly increased by L-arabinose ( P < 0.05). Interferon regulatory factor-5 ( IRF-5 ) and signal transducer and activator of transcription-1 ( STAT-1 ), key genes characterized by M1 macrophages, were elevated in the jejunum and colon of LPS mice ( P < 0.05) but decreased in the ARA+LPS mice ( P < 0.05). In vitro , L-arabinose decreased the proportion of M1 macrophages and inhibited mRNA levels of TNF-α , IL-1β , IL-6 , IFN-γ , as well as IRF-5 and STAT-1 ( P < 0.01). Moreover, L-arabinose restored the abundance of norank_ f__Muribaculaceae , Faecalibaculum , Dubosiella , Prevotellaceae_UCG-001 , and Paraasutterella compared with those of LPS ( P < 0.05) and increased the concentration of short-chain fatty acids ( P < 0.05). Conclusion The anti-inflammatory effects of L-arabinose are achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.
研究领域:
免疫学
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胃肠病学
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营养学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2021
·Vol. 11
·期 1
·1-13
·
IF 7.133
Tang Ying,Zhou Mengchun,Huang Rongrong,Shen Ling,Yang Li,Zhou Zhongqiu,Ren Hui,Bai Ying
Background Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown. Results Here, we demonstrated that HECTD1 was upregulated in primary mouse astrocytes after 100 ng/ml lipopolysaccharide (LPS) treatment. Genetic knockdown of HECTD1 in vitro or astrocyte-specific knockdown of HECTD1 in vivo suppressed LPS-induced astrocyte activation, whereas overexpression of HECTD1 in vitro facilitated LPS-induced astrocyte activation. Mechanistically, we established that LPS activated σ-1R-JNK/p38 pathway, and σ-1R antagonist BD1047, JNK inhibitor SP600125, or p38 inhibitor SB203580 reversed LPS-induced expression of HECTD1, thus restored LPS-induced astrocyte activation. In addition, FOXJ2 functioned as a transcription factor of HECTD1, and pretreatment of primary mouse astrocytes with BD1047, SB203580, and SP600125 significantly inhibited LPS-mediated translocation of FOXJ2 into the nucleus. Conclusions Overall, our present findings suggest that HECTD1 participates in LPS-induced astrocyte activation by activation of σ-1R-JNK/p38-FOXJ2 pathway and provide a potential therapeutic strategy for neuroinflammation induced by LPS or any other neuroinflammatory disorders.
研究领域:
神经科学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
RENAL FAILURE
·
2025
·
IF 3
Shu Zhang,Xin Dong,Gangyi Chen,Chao Wang
Background Oxidative stress is a critical pathological mechanism in septic acute kidney injury (AKI). Tanshinone IIA (Tan IIA), a bioactive compound derived from Salvia miltiorrhiza, exhibits antioxidative properties. This study aimed to explore the protective mechanisms of Tan IIA in septic AKI.Methods A mouse model of lipopolysaccharide (LPS)-induced AKI was established, with Tan IIA administered prior to LPS injection. Renal function was assessed by serum creatinine and urea nitrogen levels, while histopathological damage and apoptosis were evaluated using PAS and TUNEL staining. Oxidative stress was assessed by SOD activity, ROS levels, and 8-OHdG staining. In vitro, LPS-stimulated HK-2 cells were treated with Tan IIA or RIP3 siRNA. The expression of RIP3, p-RIP3, Nrf2, HO-1, KEAP1, and downstream antioxidant genes (NQO1, GCLC) was analyzed by qRT-PCR, immunohistochemistry, and Western blot. Apoptosis was further evaluated by Annexin V-FITC/PI flow cytometry and detection of apoptosis-related proteins (Bax, cleaved caspase-3, Bcl-2). Co-immunoprecipitation was performed to examine RIP3–Nrf2 interaction.Results In vivo, Tan IIA significantly improved renal function and alleviated tubular damage. It decreased ROS production and 8-OHdG positivity while restoring SOD activity. In vitro, Tan IIA or RIP3 silencing decreased ROS levels, enhanced SOD activity, promoted Nrf2 nuclear translocation, and upregulated antioxidant genes. Flow cytometry confirmed reduced apoptotic cell populations, and Western blot showed reversal of LPS-induced pro-apoptotic protein changes. The co-immunoprecipitation confirmed an interaction between RIP3 and Nrf2 under LPS stimulation.Conclusion These findings suggest that Tan IIA protects against LPS-induced AKI by inhibiting RIP3 expression and restoring Nrf2-mediated antioxidant defenses, thereby attenuating oxidative stress and apoptosis.
研究领域:
药理学
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肾脏病学
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分子生物学
·
氧化应激研究
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炎症
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Cuicui Duan,Hongru Wang,Yi Zhang,Hui Liu,Siyang Sui,Mengchun Qin,Xiaolei Li,Fumin Ma,Dan Li
Lactobacillus exopolysaccharides (EPS) have been widely used in fermented food and health care products due to their good biological activities. In this study, EPS derived from Lactobacillus plantarum A106 and β-lactoglobulin (β-Lg) were used to prepare β-Lg-EPS complex, and the structure and antioxidant activity of the complex were studied. The results indicated that the incorporation of EPS with β-Lg could quench the inherent fluorescence of β-Lg and change the conformation and secondary structure, finally improving the thermal stability. Moreover, addition of EPS changed the spherical structure of β-Lg, and the structure of β-Lg-EPS complexes appeared blocky and dendritic. Both ζ potential and particle size of β-Lg-EPS complex were decreased regardless of proportions between β-Lg and EPS. The dispersion system was the most uniform and stable when the ratio of β-Lg to EPS was 10:1. Moreover, β-Lg-EPS complex presented a higher free radical scavenging rate than that of native β-Lg, 64.47 ± 2.77 % for DPPH, 90.09 ± 0.42 % for ABTS + and 26.74 ± 0.56 % for ·OH, respectively. Moreover, β-Lg-EPS complex could alleviate oxidative damage and exert its antioxidant activity by improving cell viability and SOD activity, reducing ROS level, restoring mitochondrial membrane potential and improving apoptosis of LPS-induced RAW264.7 cells.
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DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Cao Jie,Zhang Jing,Yan Ling,Liu Changhong,Wang Yaqian,Cao Yaqi,Zheng Lei
Excessive inflammation and oxidative stress can accelerate inflammatory disease. Plant exosome-like nanoparticles demonstrate therapeutic capacity for anti-inflammatory and antioxidant effects. Here, the effects of red cabbage exosome-like nanoparticles (RELNs) on inflammation and oxidative stress triggered by LPS in macrophages were investigated. RELNs inhibited the expression of the TLR4/NF-κB pathway and blocked the entry of NF-κB p65 from the cytoplasm into the nucleus. Additionally, RELNs reduced the ROS level, alleviated oxidative damage in mitochondria, and increased antioxidant enzyme activity in macrophages. Importantly, RELNs promoted the expression of the Nrf2/Keap1 pathway-mediated antioxidant genes and increased the entry of Nrf2 from the cytoplasm into the nucleus. The research further demonstrated that RELNs might be dependent on Nrf2 expression to decrease the inflammatory response. In brief, RELNs could reduce LPS-induced macrophage inflammation and oxidative stress in vitro, suggesting the therapeutic potential of RELNs in clinical inflammatory diseases. Graphic abstract
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PubMed
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 9
·e70881
·
IF 3.8
Zhuohui Luo,Zaibin Xu,Kongyan Wang,Huiyu Hu,Jiawen Huang
Citri Sarcodactylis Fructus (CSF), an ornamental and edible fruit belonging to the genus Citrus in the Rutaceae family, has been shown to exhibit anti‐inflammatory, antioxidant, and anti‐obesity effects. However, its impact on the progression of acute lung injury (ALI) remains unclear. In this study, CSF significantly alleviated LPS‐induced pulmonary edema in ALI mice and improved oxidative stress markers, as evidenced by reduced serum malondialdehyde (MDA) levels and increased serum superoxide dismutase (SOD) levels. It also decreased macrophage and neutrophil counts as well as protein levels in bronchoalveolar lavage fluid (BALF), and inhibited inflammatory responses‐specifically, it reduced the protein and gene expression of IL1β, IL6, and TNF‐α in lung tissues, downregulated the mRNA levels of chemokines, and suppressed LPS‐induced activation of NF‐κB signaling. Moreover, CSF significantly reduced NLRP3 inflammasome activation. The components of CSF exhibit high binding activity and stability to NF‐κB p65 or NLRP3, along with low binding free energy, within their respective binding pockets. This study reveals that CSF alleviates LPS‐induced ALI by inhibiting NF‐κB signaling and NLRP3 inflammasome activation‐mediated inflammatory response, thereby providing a scientific basis for the utilization of CSF resources. Citri Sarcodactylis Fructus (CSF) has been shown to exhibit anti‐inflammatory, antioxidant, and anti‐obesity effects. However, its impact on the progression of acute lung injury (ALI) remains unclear. This study reveals that CSF alleviates LPS‐induced ALI by inhibiting NF‐κB signaling and NLRP3 inflammasome activation‐mediated inflammatory response, thereby providing a scientific basis for the utilization of CSF resources.
研究领域:
药理学
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免疫学
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植物学
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分子生物学
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呼吸系统疾病
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）