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.
研究领域:
药理学
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免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2019
·
IF 3.559
Haihua Zhang,Haijun Gu,Qinghui Jia,Yanqing Zhao,Hongqiang Li,Shurui Shen,Xin Liu,Guisheng Wang,Qiumei Shi
Inflammatory bowel disease (IBD) is a chronic inflammatory condition with high incidence. Syringin exhibits multiple pharmacological properties, including anti-inflammatory effects. However, the effect of syringin on inflammation of IBD is still unclear. Here, the dextran sulfate sodium (DSS)-induced colitis model was established in vivo . Rat intestinal epithelium IEC6 cells were treated with lipopolysaccharide (LPS) in vitro . Syringin inhibited DSS or LPS-induced overproduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and proinflammatory substances (iNOS, COX-2). Moreover, syringin inactivated the proinflammatory NF-κB p65 pathway by decreasing IκBα phosphorylation at Ser 32. The activation of antioxidant Nrf2 signaling pathway was promoted by syringin. Additionally, LPS-induced inflammation in IEC6 cells was also suppressed by NF-κB inhibitor PDTC and Nrf2 activator RTA408. The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Xuepeng Gong,Dong Liu,Lu Liu,Guangjie Yang,Yongfang Lei,NingHong Li,Yufei Chen,Hengyi Yu,Xiping Li,Dong Xiang
Bile acids (BAs), not only promote the absorption of fat-soluble nutrients and regulate the metabolism of multiple substances but also have a potential role as diagnostic and prognostic indicators in a variety of diseases such as cholestasis, hepatocellular carcinoma, and diabetes mellitus. Here, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 50 BAs was developed and validated. Sample preparation included internal standard spiking, followed by protein precipitation, centrifugation, solvent evaporation, and reconstitution. Baseline separation of all isobaric BA species was achieved on an Ultimate XS-C18 column (5 μm, 150 mm × 4.6 mm). The method showed good linearity with high regression coefficients (>0.990) with acceptable accuracy and precision for intra-day and inter-day analyses and achieved good recovery rates for representative analytes. No apparent carryover or matrix effect was observed. The analytical method was successfully applied to the determination of the plasma BA profile in healthy subjects and patients with inflammatory bowel disease (IBD). The routine instrumentation, low sample volume, simple pretreatment, wide range of BAs, and good separation make this LC-MS/MS method suitable for use as a BA profile assay in clinical and basic research studies. This method could be poised to identify possible BA biomarkers for non-invasive early diagnosis and therapeutic evaluation of IBD.
研究领域:
临床医学
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分析化学
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Min Xu,Xuan Zhang,Liqun Wei,Yimei Zhang,Xiaole Yin,Nan Meng,Bing Zhang,Weihong Zhao,Zhihuan Zhao
Intestinal microecological disruption, characterized by a vicious cycle of epithelial barrier dysfunction and microbial dysbiosis, is a critical driver of inflammatory bowel diseases (IBD). A compromised epithelial barrier facilitates the invasion of pathogens, which further exacerbates the mucosal damage through immune response and inflammatory cascades. Herein, an oral, hierarchically pH-responsive metal-polyphenol nanocomplex (Zn-GA@ES100) with synergistic antimicrobial and barrier-restoring functions is developed to interrupt this cycle. The nanocomplex is founded on a “carrier-is-the-drug” principle, where a core nanoparticle composed of zinc ions (Zn 2+ ) and gallic acid (GA) is coated with an enteric Eudragit® S100 (ES100) shell. ES100 protects the nanocomplex from gastric acid, dissolving only in the intestine. Upon reaching the acidic microenvironment of inflamed sites, the Zn-GA core specifically disassembles to release Zn 2+ and GA. Zn 2+ selectively suppresses the expansion of pathogenic bacteria ( E. coli and S. aureus ) to regulate the gut microbiome, while GA enhances epithelial barrier integrity by increasing tight junction (TJ) proteins (claudin-5, occludin-1, and ZO-1) via the Nrf2/HO-1 pathway. Consequently, Zn-GA@ES100 demonstrates potent therapeutic efficacy in a DSS-induced colitis model, efficiently reprogramming the gut microecology by concurrently eliminating pathogens and repairing the epithelial barrier. This nanoplatform highlights a powerful and precise therapeutic strategy for IBD.
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高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Guijie Chen,Mingjia Wang,Ziqi Zeng,Minhao Xie,Weiqi Xu,Yujia Peng,Wangting Zhou,Yi Sun,Xiaoxiong Zeng,Zhonghua Liu
The purified fraction 3 of polysaccharides from Fuzhuan brick tea (FBTPS-3) could attenuate the colitis and modulate the gut microbiota. However, the relationship between anti-inflammatory effect of FBTPS-3 and the gut microbiota is still unknown. Thus, the anaerobic fermentation in vitro was used to investigate the potential mechanism. FBTPS-3 could be utilized and degraded by gut microbiota from inflammatory bowel disease (IBD) subjects. Furthermore, FBTPS-3 could modulate the composition and structure of IBD gut microbiota toward to that of healthy group. FBTPS-3 showed a superior modulated effect on IBD gut microbiota by increasing Bacteroides and decreasing Escherichia/Shigella . Furthermore, the fermentation solution rather than FBTPS-3 itself showed anti-inflammatory effects on lipopolysaccharide-treated RAW264.7 macrophages, which might be due to the metabolites such as short-chain fatty acids (SCFAs). Thus, FBTPS-3 can be expected as novel prebiotics for treatment of IBD via modulating gut microbiota, and promoting the production of SCFAs.
研究领域:
微生物学
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营养学
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胃肠病学
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DOI
PubMed
高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2020
·Vol. 66
·期 10
·3375-3390
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IF 2.751
Zhang Yu,Li Xiaozhi,Li Yaoting,Li Ying,Wang Ying,Zhu Liguo,Chen Peng,Tian Zhenyi,Qiu Yun,Feng Rui,Zeng Zhirong,He Yao,Chen Baili,Zhang Shenghong,Mao Ren,Chen Minhu
Background and Aims DNA damage-regulated autophagy modulator 1 (DRAM1) is required for induction of autophagy and apoptosis. However, the influence of DRAM1 on the pathogenesis of inflammatory bowel disease (IBD) has not been explored. Methods DRAM1 expression was examined in the intestinal mucosa of patients with IBD and colons of colitis mice. We used a recombinant adeno-associated virus carrying small hairpain DRAM1 to knock down the DRAM1 gene to treat colitis in the mice. The effect of DRAM1 on autophagy and apoptosis of intestinal epithelial cells was explored. DRAM1-mediated interaction with the c-Jun N-terminal kinase (JNK) pathway was also examined. Results DRAM1 expression in the intestinal mucosa of the IBD patients was higher than that in the control participates. DRAM1 expression in the inflammatory cells in patients with Crohn’s disease (CD) was lower than that in patients with ulcerative colitis (UC). Additionally, DRAM1 expression was correlated with the Simple Endoscopic Score for CD and the Mayo endoscopic score for UC. Serum levels of DRAM1 in the IBD group were substantially higher than those in the normal group. The knockdown of DRAM1 could alleviate colitis symptoms in mice. In in vitro experiments, knocking down DRAM1 could reduce autophagy and apoptosis levels. Mechanistically, DRAM1 may participate in the regulation of these two processes by positively regulating JNK activation. Conclusions During intestinal inflammation, the upregulation of DRAM1 may promote the activation of JNK and further aggravate intestinal epithelium damage.
研究领域:
胃肠病学
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分子生物学
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免疫学
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病理学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 06
·1527-1546
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IF 5.7
Cheng-Xi Li,Yu-Meng Wang,Wen-Jing Zhang,Shu Zhang,Jian-Ping Li,Tong Zhou,Jin-Ao Duan,Jian-Ming Guo
Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10 − ∕ − ). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF- α levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10 − ∕ − mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae , Sutterellaceae , Erysipelotrichaceae , Burkholderiaceae , Desulfovibrionaceae , and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Cellular and Molecular Gastroenterology and Hepatology
·
2024
·
IF 7.1
Liang Wang,Jinsong Li,Mingshan Jiang,Yue Luo,Xiaoke Xu,Juan Li,Yang Pan,Hu Zhang,Zhi-Xiong Jim Xiao,Yang Wang
Background and Aims Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to Inflammatory Bowel Disease (IBD). The NAD + -dependent deacetylase SIRT1 is implicated in inflammation and the pathological process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. Methods The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and WT mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes were analyzed. Intestinal permeability was measured by FITC-Dextran and cytokines expression was analyzed by QPCR. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of Nicotinamide mononucleotide (NMN) in DSS-induced mice colitis were investigated. Correlations of the SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. Results Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. the activation of SIRT1 by NMN bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS down-regulates SiRT1 expression, leading to destabilization of β-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. Conclusion SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the β-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.
研究领域:
胃肠病学
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免疫学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yingjie Chen,Yuhan Gao,Kaiyuan Huo,Zhaofan Jin,Wenchao Wang,Xingjie Zan,Yanlong Liu,Limeng Zhu,Jianfeng Yang
Inflammatory bowel disease (IBD) is a chronic inflammatory disease with limited therapeutic outcomes. Macrophages are the key gatekeepers of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages are recognized as attractive targets to develop new therapeutic. However, the therapy development has proven challenging due to the malignant biological chain between macrophage immune hyperresponsiveness and dysbiosis of intestinal microflora. Herein, a carrier-free nano-drug, PCNPs@PEG-Man, with dual-targeting function, is produced due to IBD lesion-specific positive charge and high expression of mannose receptor. With super resistance against extreme intraluminal conditions, PCNPs@PEG-Man showes stable ROS-scavenging properties thereby. Notably, the dual-targeting strategy enhances the endocytosis efficiency and intestinal retention time of the drug, which is conducive to the downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, and repair of the intestinal barrier. Additionally, it reshaped the dysbiosis of intestinal bacteria, revealing an optimized gut flora composition of probiotics. The mechanism of the carrier-free nano-drug mainly involves the elimination of oxidative stress, promoting macrophage M2 polarization, and restoring gut homeostasis. The synergistic effect inherent in this dual-targeting system presents an effective and safe approach to managing IBD, providing new insights into the treatment of intestinal ROS-mediated diseases associated with microbiota dysbiosis.
研究领域:
纳米医学
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免疫学
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胃肠病学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Qianru Gao,Weiyi Tian,Huabing Yang,Haiming Hu,Junping Zheng,Xiaowei Yao,Baifei Hu,Hongtao Liu
Ethnopharmacological relevance Shen-Ling-Bai-Zhu-San (SLBZS) is a classic formula for strengthening the spleen and dispelling dampness, which has shown excellent efficacy in inflammatory bowel disease (IBD) in traditional Chinese medicine clinical studies. However, its exact pharmacological mechanism needs to be further elucidated. Aim of the study This study aims to investigate the restorative effect and mechanism of SLBZS on disturbed intestinal homeostasis in DSS-induced colitis mice. Materials and methods A colitis model was induced by 3% dextran sulfate sodium (DSS) for seven days, and SLBZS was administered by gavage. The influence of SLBZS on DSS-induced clinical symptoms and disease activity index (DAI) was monitored and analyzed. Alcian blue and fluorescein isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA) staining were used to assess intestinal mucus changes. The expression of intestinal barrier function indexes and immune-associated indexes were determined by H&E staining, real-time quantitative PCR (RT-qPCR), and Western blot. And gut microbiota changes were detected by 16 S rDNA sequencing technology. The antibiotic experiment was used to explore the role of gut microbiota in SLBZS treatment. Results The results showed that SLBZS significantly improved the physiological indexes including body weight, DAI score, and colon length of colitis mice. We focused on the effects of SLBZS on intestinal homeostasis in colitis mice. First, SLBZS could enhance the secretion of intestinal mucin and the expression levels of tight junctions and adhesive junctions. Second, SLBZS inhibited the expression level of inflammatory factors and reduced the protein expression level of NLRP3 inflammasome. Third, 16 S rDNA sequencing analysis revealed that SLBZS repaired the dysfunctional gut microbiota of colitis mice, such as enhancing the abundance of short-chain fatty acid-producing bacteria including Faecalibaculum , Colidextribacter , and Coprococcus . Further, by gut microbiota-depleted mice, we found that SLBZS could not exert an anti-colitis effect when gut microbiota was absent. Conclusions SLBZS restored intestinal environmental homeostasis by enhancing intestinal barrier function, inhibiting NLRP3 inflammasome, and restoring disturbed gut microbiota. And SLBZS could not ameliorate colitis mice with depleted gut microbiota. Our finding provided a theoretical basis for the clinical application of SLBZS in IBD.
研究领域:
药理学
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免疫学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Lin Niu,Shilong Wang,Yanyan Xu,Xingwang Zu,Xinyu You,Qiuyang Zhang,Pengwei Zhuang,Min Jiang,Jie Gao,Xiaotao Hou,Yanjun Zhang,Gang Bai,Jiagang Deng
Ethnopharmacological relevance As a classic traditional Chinese medicine , Magnolia officinalis ( M . officinalis ) is widely used in digestive diseases . It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. Aim of the study In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M . officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M . officinalis extract in treating IBD. Materials and methods To reveal the connection between the active ingredients in M . officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. Results Our finding elucidated that the inhibitory activity of M . officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. Conclusions The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 45
·2004692
·
IF 16.836
Sheng Zhao,Yixuan Li,Quanyi Liu,Sirong Li,Yuan Cheng,Chaoqun Cheng,Ziying Sun,Yan Du,Christopher J. Butch,Hui Wei
Safe, effective, and convenient administration of therapeutic nanomaterials is one of the greatest difficulties in nanomedicine. To tackle this challenge, a system which couples multi-enzyme mimicking CeO 2 nanoparticles with clinically approved montmorillonite (MMT) for inflammatory bowel disease (IBD) therapy is reported. CeO 2 exhibits superoxide dismutase- and catalase-like activities, and hydroxyl radical scavenging activity, making it more efficient at scavenging reactive oxygen species (ROS) than non-catalytic antioxidants while being more stable than free enzymes. In addition, negatively-charged MMT can be orally administered and specifically adsorbed onto positively-charged inflamed colon tissue via electrostatic interactions for targeted delivery. When the two are assembled together by in situ growth of CeO 2 onto MMT, the optimized CeO 2 @MMT(1:9) is stable in the stomach for oral delivery, targets the inflamed colon through electrostatic interactions, and reduces inflammation through ROS scavenging, all without any significant systemic exposure as demonstrated by the relief of murine IBD in vivo.
研究领域:
纳米医学
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药理学
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炎症研究
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治疗递送系统
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）