Food Bioscience
·
2024
·
IF 4.8
Huanhuan Liu,Jiahui Li,Chunhong Yan,Jiaxiu Liu,Dongyun Zhao,Shugang Li,Xiaodong Xia
Inflammatory bowel disease is characterized by compromised epithelium barrier function and hyperactive intestinal inflammation. This study aims to investigate the effects of punicalagin, a bioactive ellagitannin in pomegranate, on dextran-sodium sulfate (DSS) - induced colitis in mice and to examine the underlying mechanisms involved. Oral administration of punicalagin (100 mg/kg/day) effectively mitigated the severity of experimental colitis in mice, evidenced by increased colon length, improved intestinal permeability, and decreased histological scores. Punicalagin up-regulated the mRNA expression level of Muc2 in and the protein expression of zonula occludens-1 (ZO-1) and Occludin in colitic mice. Moreover, punicalagin effectively decreased reactive oxygen species (ROS) levels in the colon, and in Caco-2 cells exposed to H 2 O 2 in vitro . Mechanistically, punicalagin attenuated inflammation by inhibiting the secretion of interleukin-6 (IL-6) and the phosphorylation of the NF-κB/STAT3 pathway. In addition, punicalagin increased adenosine monophosphate activated protein kinase (AMPK) phosphorylation in the colon of DSS-treated mice and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages. Knocking down AMPKα by siRNA diminished punicalagin's anti-inflammatory function in RAW 264.7 macrophages exposed to LPS. Furthermore , molecular docking analysis, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) analysis supported the direct interaction between punicalagin and AMPK. In conclusion, punicalagin could mitigate DSS-induced colitis through enhancing intestinal epithelial barrier, alleviating oxidative stress, and attenuating inflammation partly through modulation of AMPK–NF–κB-STAT3 pathway.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
DOI
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 11
·2400275
·
IF 3.7
Yao Yao,Binqing Xue,Duncan James Lessing,Weihua Chu
Alterations in the intestinal microenvironment, including increased levels of reactive oxygen species (ROS), abnormalities in intestinal mucosal immune regulation, and dysbiosis of the intestinal microbiota, are crucial to the development of inflammatory bowel disease (IBD). Herein, an oral colon-targeting Se-Probiotic@Alginate bead (BLSe) with ROS-scavenging ability and gut immune-microbiota microenvironment remodeling ability is developed using alginate as the primary outer shell encapsulated with probiotics Bacillus licheniformis (BL) and selenium nanoparticles stabilized by yeast glucan (SeNPs). In vitro studies have shown that SeNPs possess antioxidant activity and BLSe exhibits excellent stability in gastric fluids and are released in intestinal fluids. In vivo studies have also shown that BLSe significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inhibiting colon shortening, enhancing antioxidant activity, reducing pro-inflammatory cytokine secretion, and protecting the intestinal mucosal barrier. 16S ribosomal RNA sequencing shows that BLSe can remodel the composition of the gut microbiota by improving bacterial diversity and restoring the relative abundance of beneficial bacteria in the colon. Overall, this study advances a promising probiotic-based nanomedicine for managing IBD.
研究领域:
药学
·
免疫学
·
微生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Weiqin Wang,Xuefeng Li,Fanli Shi,Zhenhai Zhang,Huixia Lv
In this study, γ-cyclodextrins (γ-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-γ-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of γ-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-γ-IC effectively inhibited the secretions of NO, TNF-α, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-γ-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1β, IL-6, and TNF-α in serum, and restoring MPO , GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-γ-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and γ-CD alone. Therefore, EGCG-γ-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.
研究领域:
药学
·
炎症性肠病
·
药物递送系统
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Zhiyong Xie,Ziqi Zeng,Guijie Chen,Wei Dong,Yujia Peng,Weiqi Xu,Yi Sun,Xiaoxiong Zeng,Zhonghua Liu
The intracellular polysaccharides of Aspergillus cristatus (IPSs) from Fuzhuan brick tea have been demonstrated to improve immune function linked to modulating the gut microbiota. Herein, to further investigate the efficacy of IPSs to maintain gut homeostasis, the protection of the purified fraction of IPSs (IPSs-2) on the mice with colitis induced by dextran sulfate sodium (DSS) and the underlying mechanisms were explored in this study. The results revealed that IPSs-2 alleviated the typical symptoms of colitis and suppressed the excessive inflammatory mediators, regulating the genes related to inflammatory responses in the colon at the mRNA level. Meanwhile, IPSs-2 treatment reinforced the intestinal barrier function by ameliorating the DSS-induced histological injury, facilitating the differentiation of goblet cells to enhance Mucin-2 generation, and enhancing the expression of tight junction proteins to alleviate colitis. In addition, IPSs protected against colitis by promoting the production of short-chain fatty acids (SCFAs), the activation of SCFAs receptors, and the leverage of the gut microbiota via the enrichment of Bacteroides, Parabacteroides, Faecalibacterium, Flavonifractor_plautii, and Butyricicoccus, linking with reducing inflammation and repairing intestinal barrier function. Overall, our research revealed the therapeutic potential of IPSs-2 as a prebiotic for attenuating inflammatory bowel disease and provided a rationale for future investigation.
研究领域:
免疫学
·
微生物学
·
药理学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Jindan Xiao,Liuming Xie,Bing Zheng,Wenjie Ma,Yi Chen,Jianhua Xie,Xiaobo Hu,Qiang Yu
Autophagy is pivotal for the management of intestinal homeostasis, modulation of intestinal immunity response and anti-microbial protection. Previous studies have documented the protective function of Polygonatum cyrtonema Saponin (PCS) against intestinal injury, but whether PCS modulated autophagy and its associated responses remained unknown. A model of dextran sodium sulfate (DSS)- elicited intestinal injury was employed to confirm this hypothesis. The results showed that PCS effectively relieved the typical symptoms of DSS-induced weight reduction, shortened colon length, and augmented disease activity index score, down-regulated organ indices, reduced hepatic oxidative stress, and inhibited excessive inflammatory mediators. Meanwhile, PCS intervention ameliorated the intestinal barrier dysfunction via promoting the differentiation of goblet cells and augmenting the expression of tight junction proteins (TJs). It also suppressed apoptosis in intestinal cells by altering the Bcl-2/Bax ratios and diminishing the expressions of Caspase-9 and Caspase-3. Additionally, PCS remarkably enhanced autophagy by modulating the PI3K/AKT/mTOR signal pathway. More importantly, the classical autophagy inducer rapamycin augmented the beneficial effects of PCS. In contrast, the autophagy inhibitor 3-methyladenine essentially eliminated the above effects, revealing a role for autophagy in the response. Further studies have demonstrated that PCS intervention improved the diversities of the intestinal flora, increased occupancy of beneficial bacteria in Lachnospiraceaeae and Akkermansia , which was closely associated with autophagy. Taken together, these findings demonstrated that PCS is a potential supplier of prebiotics by modulating immunity, repairing intestinal mucosal injury, regulating autophagy and intestinal flora, and autophagy is a key target for PCS-mediated intestinal barrier protection.
研究领域:
胃肠病学
·
免疫学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2019
·
IF 4.708
Jin Cao,Jin Cheng,Siyu Xi,Xueyong Qi,Song Shen,Yanru Ge
Targeted delivery of bioactive compounds such as proteins to the colon has numerous advantages for the therapeutic treatment of inflammatory bowel disease . The present study sought to fabricate alginate/chitosan microcapsules containing IL-1Ra (Alg/Chi/IL-1Ra MC) via a single-step electrospraying method. Two important factors of efficacy were measured—the pH-responsiveness of the microcapsule and the in-vitro drug release profile. The DSS-induced colitis mouse model was used to evaluate the therapeutic effect of the Alg/Chi/IL-1Ra microcapsules, with results showing the protective effect of the Alg/Chi microcapsules for the passage of IL-1Ra through the harsh environment of the upper gastrointestinal tract . This effect was owing to the pH-sensitive response of the microcapsule, which allowed the targeted release of IL-1Ra in the colon. DAI evaluation, colon length, colon tissue morphology, histologic damage scores and relative protein concentrations (MPO, TNF-α and IL-1β) demonstrated that the Alg/Chi/IL-1Ra microcapsules alleviated DSS-induced colitis in mice. The present study thus demonstrates a practical means of oral delivery of proteins, in-situ colon release, and a promising application of IL-1Ra in the treatment of autoimmune and inflammatory diseases .
研究领域:
药学
·
生物医学工程
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Liuming Xie,Ting Chen,Hong Li,Jindan Xiao,Linchun Wang,Soo-Ki Kim,Zhibing Huang,Jianhua Xie
Inflammatory bowel disease is a major health problem that can lead to prolonged damage to the digestive system. This study investigated the effects of an exopolysaccharide from genistein-stimulated Monascus purpureus (G-EMP) in a mouse model of colitis to clarify its molecular mechanisms and identified its structures. G-EMP (Mw = 56.4 kDa) was primarily consisted of → 4)-α-D-Galp-(1 →, → 2,6)-α-D-Glcp-(1→ and →2)-β-D-Manp-(1 → , with one of the branches being α-D-Manp-(1 →. G-EMP intervention reduced the loss of body weight, degree of colonic damage and shortening, disease activity index scores, and histopathology scores, while restoring goblet cell production and oxidative homeostasis, repairing colonic functions, and regulating inflammatory cytokines. RNA sequencing and Western blot analysis indicated that G-EMP exerts anti-inflammatory properties by suppressing the TLR4/MAPK/NF-κB inflammatory signaling pathway. G-EMP modulated the gut microbiota by improving its diversities, elevating the relative abundances of beneficial bacteria, declining the Firmicutes/Bacteroidota value, and regulating the level of short-chain fatty acids (SCFAs). Correlation analysis demonstrated strong links between SCFAs, gut microbiota, and the inflammatory response, indicating the potential of G-EMP to prevent colitis.
研究领域:
药理学
·
微生物学
·
免疫学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Shan Tian,Yugang Hu,Jinhui Zou,Nan Hao,Jian Liu,Ruixue Li,Jiao Li
Nanoplastic pollution is a serious global concern, which has caused great threat to the human health. However, the relationship between nanoplastic exposure and the development and progression of ulcerative colitis (UC) is still unknown. We established a chronic dextran sulfate sodium (DSS)-induced colitis model with exposure to polystyrene nanoplastics (PS-NPs) and evaluated disease severity, gut inflammation, and intestinal barrier function. The immune microenvironment was assessed using fluorescence multiplex immunohistochemistry (mIHC), while histone lactylation modification was analyzed via western blot and Cleavage Under Targets and Tagmentation (CUT&Tag). Additionally, lipopolysaccharide (LPS)-treated RAW264.7 cells were cultured and intervened to further investigate the molecular mechanism of PS-NPs in colitis. Continuous exposure to PS-NPs exacerbated gut inflammation and damage intestinal barrier function in DSS-induced colitis. PS-NPs exposure is closely correlated with increased macrophage infiltration, enhanced the glycolysis and up-regulated the histone H3 lactylation in macrophages. CUT&Tag analysis showed that PS-NPs influenced the expression of GART via histone H3K18la lactylation. Intervention in histone H3K18la lactylation significantly altered the expression of GART and levels of inflammatory factors in LPS-treated RAW264.7 cells. Downregulating GART expression reduced inflammatory factor levels in RAW264.7 cells treated with LPS plus PS-NPs. PS-NPs exposure exacerbates colitis by upregulating histone H3 lactylation. This study reveals a novel mechanism underlying nanoplastic-exacerbated intestinal injury and provides a direction for future risk assessment of nanoplastics.
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Xin Liu,Chunli Yan,Chunxiao Chang,Fansong Meng,Wenjie Shen,Song Wang,Yi Zhang
Background Mycotoxins, such as aflatoxin and ochratoxin A (OTA), are found at measurable levels in many staple foods; the health implications of long-term exposure of such toxins are poorly understood. Increasing evidence has confirmed the important role of OTA in upregulation of oxidative stress- and inflammatory response-induced tissue injury. However, it remains unknown whether ochratoxin A can promote chronic colitis and its associated colon cancer (CRC) development, and potential molecular mechanism. Additionally, RING finger-interacting protein with C kinase (RINCK) is a ubiquitin ligase and mediates immune response. Unfortunately, the potential molecular function of RINCK on regulation of colitis is still largely unknown. Purpose This study aims to provide mechanistic evidence that the role of RINCK in colitis and early colorectal cancer progression in response to OTA treatment via targeting nuclear factor erythroid 2-related factor 2 (NRF2). Methods The Cancer Genome Atlas (TCGA) database, GEO database, human subjects with CC phenotype and CC cell lines were used in this work. Pathological links between OTA, RINCK and treatment of CC are revealed through comprehensive means such as biological information analysis, clinical experiments, RNA-seq, and verification experiments. Results In this study, under oxidative stress in setting of colitis, we first identified RINCK as a key regulatory factor and a novel endogenous suppressor of nuclear factor erythroid 2-related factor 2 (NRF2), and we also confirm that RINCK is a NRF2 partner protein that catalyses its ubiquitination and degradation in intestinal epithelial cells (IECs). Notably, in vivo study, pathological phenotypes triggered by OTA pretreatment, accompanied by post-treatment of dextran sulfate sodium (DSS)-induced colitis was significantly mitigated by IEC-specific deficiency of Rinck , IEC- Rinck (KO) and adenovirus-associated virus (AAV)-triggered suppression of Rinck in rodent model, and lentivirus (LV)-mediated downregulation of Rinck (LV-sh Rinck ) in rabbit model, as determined by decreased endogenous reactive oxygen species (ROS) production, pro-inflammatory cytokines contents, improved body weights, reduced survival rates, restored colon length, assuasive DAI and histological scores. Inversely, transgenic mice by IEC-specific Rinck overexpression, IEC- Rinck (OE) accelerated colitis in acute or chronic colitis rodent models and in vitro experiments. Moreover, we found that OTA pretreatment-promoted azoxymethane (AOM)/DSS-induced colitis-associated early colorectal cancer (CRC) was also dramatically reduced by IEC- Rinck (KO), indicated by the decreased tumor number and corresponding KI-67 levels. Clinical samples analysis revealed that RINCK levels were greatly increased in tumor tissues of patients with CRC phenotypes. In parallel, RINCK deletion remarkably retarded the proliferation of colon cancer and tumor growth in vitro and in vivo , respectively. Mechanistically, in response to onset of colitis, RINCK directly interacts with NRF2 and promotes ubiquitin-proteasome degradation via increasing K48-linkage ubiquitin chain, thus leads in suppression of NRF2 nuclear translocation and its downstream cascade inactivation, which retards antioxidant defense. Conclusion The findings suggested that oral sub-chronic exposure of OTA significantly facilitates DSS-induced colitis and colitis-associated CRC development. These results further elucidated the potential role of RINCK in colitis progression by mediating NRF2 degradation, and could be considered as a therapeutic target for the treatment of such disease.
研究领域:
毒理学
·
免疫学
·
癌症生物学
·
分子生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2026
·
IF 6.3
Xuefei Wei,Chunhua Chen,Shaoping Nie
Bioactive galactans are widely distributed in nature, with some extensively reported for their potential in modulating gut microbiota and intestinal inflammation.However, the efficacy of different galactans in ameliorating colitis remains unclear. Our study systematically compared the effects of three nonlinear galactans (Hericium erinaceus polysaccharide, HEP; Lycium barbarum polysaccharide, LBP; larch arabinogalactan, LAG) and two linear galactans (agarose, AGR; carrageenan, CGN) on colitis in mice. The results indicated that HEP, LBP and LAG treatment significantly alleviated colitis symptoms, regulated the inflammatory cytokines and improved intestinal barrier function. Notably, they could modulate the gut microbiota by promoting the relative abundance of probiotics such as S24-7, Lactobacillus and Bacteroides, while suppressing the proliferation of pathogenic bacteria like Enterobacteriaceae. In contrast, AGR and CGN showed no significant alleviative effects on most indicators. This study highlights the efficacy of different types of galactans in treating colitis and modulating gut microbiota, providing a theoretical basis for the development of dietary polysaccharide-based intervention strategies for IBD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC GASTROENTEROLOGY
·
2024
·Vol. 24
·期 1
·1-10
·
IF 2.5
Wen Yuefei,Li Chenyang,Huang Peng,Liu Zhigang,He Yanjun,Liu Bin
Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.
研究领域:
免疫学
·
分子生物学
·
基因组学
✓ 已验证
DOI
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
·Vol. 32
·期 3
·2023-2033
·
IF 4.6
Yu Bing,Wang Ying,Tan Zekai,Hong Zhengyi,Yao Lewen,Huang Shiyuan,Li Zexi,Zhang Lanyue,Li Hui
Objective and design Ulcerative colitis (UC) is a multi-faceted, recurrent immune disorder caused by dextran sulfate sodium (DSS). The intestinal microbiota has multiple functions in the host, so UC requires long-term potent medication. The effect of resveratrol (RSV) has seldom been reported, and this study researched that. Herein, the effect of RSV and Grape seed oil that anti-inflammatory ability in experimental mice was explored, also why RSV altered Gut Microbiota has been researched. Materials and methods In this experiment, the effects of experimental drugs on colon length in mice with DSS-induced colitis were compared. H&E Staining was performed on serial sections of colon tissues and histological scores were determined for all groups. The expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the colon tissue of mice was detected by immunohistochemical staining. In the end, the α-diversity index, sobs index, and rarefaction curve of the cecal and colon microbiota of different groups of mice were measured. Bray–Curtis-based Venn diagram of PCoA (principal coordinate analysis) and OTUs distribution in mouse gut microbiota were obtained. Results The results showed that the use of 40 mg/kg RSV (high dose) significantly reduced the severity of UC. The use of 10 mg/kg RSV (low dose) significantly reduced the effect of shortened colon length in DSS mice. Compared with the DSS-treated group, the levels of COX-2 and TNF-α in the colon tissues of RSV + DSS-treated mice were significantly decreased. According to this experiment, 19 mouse gut microbiota species had a relative abundance greater than 0.1%, with Beerella, Bacteroides, Helicobacter, Oscillator, and cecum pylori being more abundant in the colon than in the colon. A higher relative abundance of Lachnospira NK4A136 was observed in DSS and RSV groups compared with the control group, whereas the opposite was observed for Alloprevotella. This proves that resveratrol increases the uniformity and diversity of gut microbes to a certain extent, and has a protective effect on the gut.
研究领域:
医学
·
微生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）