Food & Function
·
2024
·
IF 5.1
Xin Wang,Jing Zhang,Ruimin Zhong,Gangchao Li,Hongjin Qi,Yong Cao,Yaqi Lan
This study investigated the effect of oleogel consumption on lipid metabolism, gut microbiota and low-grade inflammation in rats fed by high-fat diet. Male SD rats received a control diet or high-fat diets for six weeks. High-fat diets included regular high-fat diet, high-fat diet where lard was replaced by pure sunflower oil, un-gelled sunflower oil with dispersed gelator, and gelled sunflower oil with gelator (oleogel), respectively. Results showed that consumption of oleogel significantly suppressed the weight gain and the adipose tissue accumulation, as well as lipid accumulation in serum and liver caused by a high-fat diet compared to regular fat, pure sunflower oil and un-gelled sunflower oil. Microscopy observations suggested that the white adipose tissue and liver steatosis caused by high-fat diet were also alleviated. Results from ex vivo biodistribution in rats indicated that more TAG moved downwards to the large intestine for oleogel group. In the meantime, the dysregulation of gut microbiota was restored by reducing the Firmicutes/Bacteroidetes ratio and the relative abundance of Desulfobacterota and Proteobacteria. The LPS levels in oleogel group were reduced in faeces, serum and liver. Furthermore, consumption of oleogel alleviated the inflammation, including decreased gene expression level of pro-inflammation cytokines, i.e., IL-6 and TNF-α, as well as suppressed protein expression of TLR4 and NF-κB in the liver. These results provided theoretical guidance for regulation of oleogel properties and the application of oleogels as healthy fat replacers in high-fat diet.
研究领域:
营养学
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微生物学
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代谢学
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食品科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yufeng Zhang,Yini Huangfu,Ling Xu,Zhezhe Zhao,Qi Su,Hui Li,Yumin Zhang,Chuangnian Zhang,Pingsheng Huang,Anjie Dong,Zujian Feng,Weiwei Wang
Antimicrobial-resistant (AMR) Gram-negative bacteria emerge due to the overuse of antibiotics. Moreover, current bactericidal drugs or materials inevitably associate with the immunologic risks from the lipopolysaccharide (LPS) released by dead bacteria, which initiates and exacerbates chronic tissue-destructive hyperinflammation, leading to treatment failure. In this study, we describe an orchestrated pH-sensitive cationic polymer nanoparticle encapsulated with rifampicin and toll-like receptor (TLR) siRNA (RNP/siRNA) that exhibits antibacterial and LPS-detoxifying characteristics for treating infected diseases. Under acidic conditions, RNP/siRNA nanoparticle releases rifampicin and cationic polymers displaying synergistically inhibitory activity against AMR bacteria by disrupting bacterial membranes, and facilitating the entry of antibiotics. Furthermore, RNP/siRNA nanoparticle exhibits high cellular uptake and TLR knockdown efficiency, thereby detoxifying the etiological LPS in M1-type macrophages polarization and reducing proinflammatory cytokines. In a mouse pneumonia model, RNP/siRNA nanoparticle treatment inhibits bacterial growth, suppresses inflammation and reduces leukocyte recruitment. In a rat periodontitis model, the administration of RNP/siRNA downregulates proinflammatory cytokines expression and inhibits bone resorption. This work highlights the elevated LPS release is an early trigger of hyperinflammation during the antibacterial process of currently established antimicrobials. The RNP/siRNA nanoparticle represents a promising strategy by integrating antibiosis and immunomodulation in a cascading manner for the treatment of bacterial infections.
研究领域:
医学
·
药学
·
免疫学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 9
·1319
·
IF 4.8
Xiaoxiao Chen,Jing Tang,Shijie Zhan,Yixian Qiu,Jing Li,Weiguang Shan,Youmin Ying
Background/Objectives:Acute lung injury (ALI) is a respiratory disorder lacking specific targeted therapy. Our preliminary screening revealed that the ethanol extract of the seeds ofPodocarpus nakaii(EESPN) alleviated the symptoms of ALI in mice. The objectives of this study were to identify the active constituents in EESPN and study the mechanism involved.Methods:Column chromatography was performed to separate the chemical constituents of EESPN. The structures of the isolates were determined via spectroscopic methods. MTT assays, Western blotting, histological analysis, TUNEL assays, immunofluorescence staining, transcriptomic analysis, and quantitative real-time polymerase chain reaction (qRT–PCR) were employed to evaluate the anti-inflammatory activity and to elucidate the potential mechanism of nagilactone C (3, Nag C) in ALI treatment.Results:Twelve compounds were isolated from EESPN and structurally characterized. The structure of podolactone E (1) was confirmed via single-crystal X-ray diffraction. In vitro, Nag C showed potent anti-inflammatory activity in LPS-induced RAW 264.7 cells. Nag C liposomes significantly ameliorated LPS-induced histopathological damage to the lungs, reduced neutrophil infiltration and inflammatory cytokine levels, increased myeloperoxidase (MPO) activity, and promoted apoptosis in mice. In addition to suppressing inflammation, Nag C also significantly suppressed the phosphorylation of the NF-κB, STAT3, and STAT1 proteins.Conclusions:Nag C is an active constituent of EESPN. It may protect against LPS-induced ALI via inhibition of the STAT signaling pathway. Thus, Nag C is a promising lead compound in the development of novel STAT-targeted anti-inflammatory agents.
研究领域:
药理学
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天然产物化学
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免疫学
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呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Pengfei Tang,Houli Jiang,Ze Zheng,Zhiqi Xiao,Lingyi Kong,Jun Luo
Background Septic acute kidney injury (S-AKI) is associated with high morbidity and mortality, and dysregulation of oxidative stress and remodeling of the inflammatory microenvironment are emerging as central pathogenic mechanisms. Alleviating inflammation and oxidative stress are the primary effects of limonoids found in nature, and our previously discovered walrobsin A (WA) from Walsura robusta has exhibited significant anti-inflammatory properties. Moreover, bioactive natural products with novel skeletons are ideal molecular probes for identifying potential novel molecular targets for diseases using chemical biology methods. Purpose To explore the therapeutic effect and mechanism of WA for treating S-AKI and to identify previously unrecognized targets in S-AKI. Methods The effect of WA was detected by establishing LPS-induced mouse S-AKI in vivo . Functional and pathological changes in murine kidneys were evaluated by measuring serum creatinine (CRE), cystatin C (Cys C), blood urea nitrogen (BUN), NGAL levels, and HE pathology. A RAW264.7/mTEC coculture system was established to elucidate the target and mechanism of WA by techniques such as RNA-seq, gene interference, DARTS, LC-MS/MS, molecular docking, BLI, and SPR. Results The screening results revealed that WA, a limonoid, significantly alleviated LPS-induced mouse S-AKI, and a RAW264.7/mTEC coculture experiment revealed that WA directly acted on macrophages. Transcriptomic analysis and further research revealed that WA promoted the expression of the antioxidant proteins HMOX1 and SOD2 and inhibited IL-1 β , IL-6, and TNF- α secretion. G protein-coupled receptor 75 (GPR75), which was highly expressed in the renal macrophages of S-AKI mice, was subsequently identified as the direct target of WA. In the RAW264.7/mTEC coculture system, siGPR75 inhibited macrophage oxidative stress and restrained IL-1 β , IL-6, and TNF- α secretion, thereby reducing mTEC injury, and overexpression of GPR75 resulted in the opposite effects. Moreover, siGPR75 reversed the WA-mediated remission of macrophage oxidative stress and the inflammatory microenvironment in vitro , and coadministration of WA failed to increase the therapeutic efficacy of 20-SOLA (a GPR75 inhibitor) in S-AKI in vivo . These results indicate that the WA-GPR75 axis mitigates S-AKI by regulating oxidative stress in macrophages and the inflammatory microenvironment. Conclusion In this study, we elucidated the novel role of GPR75 as a potential target for S-AKI using a bioactive limonoid-type natural product and identified a natural GPR75 inhibitor (WA) as a potential candidate for S-AKI treatment. This study firstly identifies GPR75 in pathological renal conditions and demonstrates its direct role in driving renal injury, thus establishing it as a novel therapeutic target for kidney diseases.
研究领域:
药理学
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免疫学
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天然产物化学
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分子生物学
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肾脏病学
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化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Kaiqin Liu,Fuwei Pi,Hongxia Zhang,Jian Ji,Shuang Xia,Fangchao Cui,Jiadi Sun,Xiulan Sun
Inflammation has been shown to play a critical role in the development of many diseases. In this study, we used metabolomics to evaluate the inflammatory effect of lipopolysaccharide (LPS) and the anti-inflammatory effect of glabridin (GB, a polyphenol from Glycurrhiza glabra L. roots) in RAW 264.7 cells. Multivariate statistical analysis showed that in comparison with the LPS group, the metabolic profile of the GB group was more similar to that of the control group. LPS impacted the amino acid, energy, and lipid metabolisms in RAW 264.7 cells, and metabolic pathway analysis showed that GB reversed some of those LPS impacts. Metabolomics analysis provided us with a new perspective to better understand the inflammatory response and the anti-inflammatory effects of GB. Metabolic pathway analysis can be an effective tool to elucidate the mechanism of inflammation and to potentially find new anti-inflammatory agents.
研究领域:
药理学
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免疫学
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代谢组学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2016
·
IF 2.73
Kegang Linghu,Dan Lin,Hong Yang,Yini Xu,Yanyan Zhang,Ling Tao,Yan Chen,Xiangchun Shen
1,8-Cineole (also known as eucalyptol) is a monoterpene that occurs naturally in many aromatic plants, 1,8-cineole has been reported to ameliorate dysfunction of endothelial cells. However, the mechanism of action of 1,8-cineole is incompletely understood. We investigated the protective effect of 1,8-cineole on lipopolysaccharide (LPS)-induced human umbilical vein endothelial cell (HUVEC) injury and the underlying mechanisms. HUVECs were preincubated with 1,8-cineole for 1.5 h, then exposed to LPS for 12 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase leakage assays showed 1,8-cineole reduced LPS-induced HUVEC injury significantly. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed LPS-induced secretion of interleukin-6 and interleukin-8, and recovered nitric oxide to normal levels. 1,8-Cineole decreased phosphorylation of nuclear factor-kappa B (NF-κB) p65 and expression of inducible nitric oxide synthase , and simultaneously improved protein levels of endothelial nitric oxide synthase . Immunofluorescence confirmed 1,8-cineole moderates nuclear translocation of NF-κB. These results suggest that 1,8-cineole ameliorates HUVEC dysfunction significantly, and that this effect at least involves NF-κB suppression.
研究领域:
药理学
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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免疫学
·
呼吸医学
·
传统中医
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2018
·Vol. 120
·期 5
·7602-7611
·
IF 2.959
Xiaolin Wang,Teng Ma,Xiaojian Wan,Yan Meng,Zhenzhen Zhao,Jinjun Bian,Rui Bao,Xiaoming Deng,Tao Yang
IGFBP7 as an early biomarker has been used to identify patients at risk of developing acute kidney injury (AKI). Nevertheless, its role in AKI remains obscure. The aim of our study is to determine the role and mechanism of IGFBP7 in lipopolysaccharide (LPS)-induced HK-2 cells in vitro and on sepsis-induced AKI by cecal ligation and puncture (CLP) in vivo. Here, we identified that IGFBP7 expression was increased in patients with AKI and HK-2 cells with LPS (1, 2, and 5 μg/mL) induction. HK-2 cells with LPS induction showed cell cycle arrest at G1-G0 phases and cell apoptosis and activated ERK1/2 parallel with the changes in the proteins belonging to the ERK1/2 pathway, including Cyclin D1, P21, Bax, and Bcl-2, which were inhibited by the IGFBP7 knockdown. Moreover, IGFBP7 overexpression significantly induced cell cycle arrest at G1-G0 phases and cell apoptosis of HK-2 cells, which were inhibited by PD98509, an ERK1/2 signaling inhibitor. IGFBP7 knockdown effectively alleviated the severity of the renal injury, evidenced by decreases in the urinary levels of creatinine, blood urea nitrogen, and albumin, cell apoptosis, and activation of ERK1/2 signaling in CLP mice. Taken together, our findings indicate that IGFBP7 regulates sepsis-induced AKI through ERK1/2 signaling.
研究领域:
肾病学
·
分子生物学
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细胞生物学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
He Sun,Jia Lou,Bo-Xue Chen,Jia-Qi Huang,Qi-Long Wang,Shao-Fei Song,Zi-Yue Jia,Rong Miao,Shi-Yu Wang,Xue Li,Wen-Zhi Yang
Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76–24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2–14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides . Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 μg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.
研究领域:
生药学
·
分析化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 8
·4276
·
IF 4.9
Chenyang Li,Xinxin Qi,Lei Xu,Yuan Sun,Yan Chen,Yuhan Yao,Jun Zhao
This study aimed to investigate the preventive effects of the total polyphenols fromNymphaea candida(NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate LPS-induced lung tissue pathological injury in mice as well as lung wet/dry ratio and MPO activities (p< 0.05). NCTP could significantly decrease the blood leukocyte, neutrophil, monocyte, basophil, and eosinophil amounts and LPS contents in ALI mice compared with the model group (p< 0.05), improving lymphocyte amounts (p< 0.05). Moreover, compared with the model group, NCTP could decrease lung tissue TNF-α, IL-6, and IL-1β levels (p< 0.05) and downregulate the protein expression of TLR4, MyD88, TRAF6, IKKβ, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, NLRP3, ASC, and Caspase1 in lung tissues (p< 0.05). Furthermore, NCTP could inhibit ileum histopathological injuries, restoring the ileum tight junctions by increasing the expression of ZO-1 and occludin. Simultaneously, NCTP could reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Clostridiales and Lachnospiraceae, and enhance the content of SCFAs (acetic acid, propionic acid, and butyric acid) in feces. These results suggested that NCTP has preventive effects on septic ALI, and its mechanism is related to the regulation of gut microbiota, SCFA metabolism, and the TLR-4/NF-κB and NLRP3 pathways.
研究领域:
药理学
·
免疫学
·
微生物学
·
病理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
LABORATORY INVESTIGATION
·
2021
·Vol. 101
·期 9
·1118-1129
·
IF 5.662
Wang Xin,Li Xing-Liang,Qin Li-Jie
Myocardial injury is a severe complication of sepsis and contributes substantially to the death of critically ill patients. Long non-coding RNAs (lncRNAs) participate in the pathogenesis of sepsis-induced myocardial injury. In this study, we investigated the role of lncRNA X-inactive specific transcript (XIST) in septic myocardial injury and explored its mechanism. Lipopolysaccharide (LPS)-stimulated H9C2 cells and rats subjected to cecal ligation and puncture (CLP) were used as the in vitro and in vivo models. After exposure to LPS, XIST and c-Fos levels were upregulated, but miR-150-5p was downregulated in H9C2 cardiomyocytes and myocardial tissues. XIST affected viability, apoptosis, and pyroptosis in LPS-challenged H9C2 cells. Moreover, XIST knockdown attenuated LPS-induced injury in H9C2 cells by targeting the miR-150-5p/c-Fos axis. c-Fos could bound to the promoter of the TXNIP/XIST gene and enhanced TXNIP/XIST expression. Silencing of XIST improved cardiac function and survival rate and reduced apoptosis and pyroptosis by regulating the miR-150-5p/c-Fos axis in septic rats in vivo. Taken together, our data show that XIST/miR-150-5p/c-Fos axis affected septic myocardial injury, which may indicate a novel therapeutic strategy for sepsis-induced myocardial injury.
研究领域:
分子生物学
·
心脏病学
·
传染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Linlin Qu,Xiaoxuan Ma,Daidi Fan
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Our previous reports showed that ginsenoside Rk3 provided excellent efficacy in alleviating the intestinal inflammatory response and protecting the liver, but its mechanism for HCC prevention remains to be explored. Here, the results suggested that Rk3 displayed potent antitumor effects against a dimethyl nitrosamine- and CCl4-induced HCC mouse model. Results revealed that Rk3 application inhibited liver injury, fibrosis, and cirrhosis. In parallel, Rk3 lowered the inflammatory response by decreasing the expression of inflammatory cytokines, inducing apoptosis, and blocking the cell cycle. Meanwhile, Rk3 effectively ameliorated the gut microbiota dysbiosis. Furthermore, correlation analysis revealed that the LPS-TLR4 signaling pathway, which was inhibited by Rk3, plays a key role in preventing HCC. To conclude, our research provides valuable insights into how Rk3 application targets the gut-liver axis and suppresses HCC development, suggesting that Rk3 might be a promising candidate for clinical treatment of HCC.
研究领域:
肿瘤学
·
药理学
·
胃肠病学
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免疫学
✓ 已验证
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）