Journal of Inflammation Research
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2025
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IF 4.1
Siyue Bo,Xiaotong Wang,Jiani Qian,Guoqiang Ma,Zheng Ying,Duanmin Hu,Chunyan Hou,Junfeng Ma,Longjiang Xu,Shuang Yang
Background Ulcerative colitis (UC) disrupts the colon’s protective mucus layer, exposing the epithelium to bacteria and triggering inflammation. This barrier, crucial for intestinal health, depends on complex glycosylation, notably sialic acid modifications. However, the precise role of sialic acid acetylation and the enzyme SIAE (sialic acid acetylesterase) in UC pathogenesis remains unclear. This study investigates the role of glycosylation changes, specifically sialic acid de-acetylation, in UC progression.Methods Tissue samples were obtained from patients with ulcerative colitis (UC) and colorectal cancer at the Second Affiliated Hospital of Soochow University. HT-29 cells were utilized to investigate the molecular mechanisms of SIAE in UC pathogenesis. Mass spectrometry was performed to analyze differences in protein and glycoprotein expression. Western blot (WB) and immunohistochemistry (IHC) were used to examine SIAE protein expression changes during inflammation. Furthermore, polymerase chain reaction (PCR) and immunofluorescence were employed to determine the effects of SIAE on sialic acid levels and mucosal immunity.Results In this study, we characterized proteins and glycoproteins from patient tissues with UC, finding that sialic acid acetylesterase (SIAE) is upregulated in UC. HT-29 cells exposed to TNF-α induced an inflammatory response with a 5-fold increased expression of SIAE and NEU1 when TNF-α was at a concentration of 100 ng/mL. Mass spectrometry analysis revealed a reduction in acetylation on glycans and glycoproteins, while confocal microscopy confirmed a decrease in sialic acid on the cell surface. Gene expression analysis showed that CDH1, CTNND1, and ITGA8 were significantly downregulated in HT-29 cells stimulated by TNF-α, suggesting a reduction in cell-cell adhesion. SNA lectin-confocal microscopy revealed a reduction of sialic acid on HT-29 cells in TNF-α-induced UC cell models.Conclusion This study demonstrates that SIAE is significantly upregulated in ulcerative colitis (UC) tissues and TNF-α-stimulated HT-29 cells, leading to a marked reduction in sialic acid acetylation and cell surface sialic acid levels. These changes correlate with decreased expression of cell adhesion molecules, suggesting a disruption of the mucosal barrier integrity. Consequently, SIAE-mediated sialic acid de-acetylation emerges as a critical factor in UC pathogenesis, potentially serving as both a valuable biomarker and a promising therapeutic target.
研究领域:
医学
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分子生物学
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免疫学
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PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Guohao Mu,Fang Peng,Ziyin Zhang,John M. Brameld,Peter Rose,Xiaogang Yang,Zhi-jiang Jiang,Xi He,Bencan Tang
This study designed and developed a novel three-layer electrostatic, slow-releasing nanoparticle drug delivery system for the treatment of ulcerative colitis. The nanoparticles were composed of layers of zein-based polydopamine, chitosan and cellulose acetate phthalate to form a polyelectrolyte multilayer core−shell nanoparticle structure. The anti-inflammatory natural product magnolol was chosen to be the model drug for the study. The nanoparticles (260.50 ± 23.90 nm) were prepared with layer-by-layer coating and then assessed in vitro and in vivo using a mouse model of ulcerative colitis. The in vitro data confirmed the slow-releasing and pH-dependent characteristics of particles. Quantitative analysis of the in vivo distribution of Mag in mice showed significantly higher concentrations in colonic tissue than in the upper gastrointestinal tract (854.6 ng/g vs 291.5–351.1 ng/g, respectively). Histological and pro-inflammatory cytokine analysis indicated that the nanoparticles had a significant anti-inflammatory effect and were protective against DSS-induced structural damage of the colonic mucosal structure. These results confirm that this nano-delivery system could increase the levels of Mag reaching the colon, resulting in greater efficacy than free Mag in treating UC in this mouse model.
研究领域:
药剂学
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炎症性肠病研究
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生物材料
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DOI
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Perumal Ramesh Kannan,Liuting Chen,Yudie Lv,Ruibo Zhao,Yeting Hu,M. Zubair Iqbal,Qianqian Han,Xiangdong Kong,Yao Li
Ulcerative colitis (UC) is a chronic inflammatory bowel disease, with untreated cases often progressing to colorectal cancer. Current treatments aim to induce inflammatory remission but often neglect the surrounding microenvironment, which significantly impairs mucosal healing and contributes to treatment failures. This study presents a novel silk fibroin-based fucoidan (SFU) in situ rectal gel, with sol-gel transition confirmed through rheological analysis under physiological pH and temperature conditions. The SFU gel exhibits strong antioxidant activity, achieving a DPPH radical scavenging rate of 73.3 ± 1.52%. The gel efficiently reduces reactive oxygen species (ROS) and nitric oxide (NO) production, demonstrating its reliable antioxidant effects. In a DSS-induced UC mouse model, SFU effectively alleviates colitis symptoms, including weight loss and disease activity index (DAI) reduction, with improved stool consistency and reduced rectal bleeding. Moreover, SFU therapy reprograms macrophages from proinflammatory M1 to anti-inflammatory M2 phenotypes, significantly lowering IL-6 and TNF-α levels, suggesting anti-inflammatory properties. Furthermore, SFU increased tight junction proteins Occludin-1 and ZO-1, indicating gut mucosal barrier integrity. SFU treatment restores goblet cells and mucin production while preventing fibrosis, demonstrating its potential as a natural therapy for UC treatment.
研究领域:
医学
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生物材料学
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DOI
PubMed
高影响因子
FASEB JOURNAL
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2025
·Vol. 39
·期 7
·e70529
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IF 4.2
Hai-Xiang Guo,Zhong-Hao Ji,Bing-Bing Wang,Yu Xiao,Jin-Ping Hu,Yi Zheng,Wei Gao,Bao Yuan
Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in vitro. It was found that Lut treatment inhibited TM/TG-induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM-treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation-related diseases in humans. Graphical Luteolin modulates endoplasmic reticulum stress by targeting SIRT1 to ameliorate ulcerative colitis in mice.
研究领域:
药理学
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炎症性疾病
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分子生物学
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DOI
PubMed
高影响因子
Foods
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2023
·Vol. 12
·期 5
·1115
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IF 5.2
Shutong Chen,Min Wang,Suresh Veeraperumal,Bo Teng,Rui Li,Zhengming Qian,Jianping Chen,Saiyi Zhong,Kit-Leong Cheong
Morchella esculentais an edible mushroom with special flavor and high nutritional value for humans, primarily owing to its polysaccharide constituents.M. esculentapolysaccharides (MEPs) possess remarkable pharmaceutical properties, including antioxidant, anti-inflammatory, immunomodulatory, and anti-atherogenic activities. The aim of this study was to evaluate the in vitro and in vivo antioxidant potential of MEPs. In vitro activity was determined using free radical scavenging assays, whereas in vivo activity was evaluated through dextran sodium sulfate (DSS)-induced liver injury in mice with acute colitis. MEPs effectively scavenged 1,1-diphenyl-2-picrylhydrazyl and 2,2-azinobis-6-(3-ethylbenzothiazoline sulfonic acid) free radicals in a dose-dependent manner. Additionally, DSS-induced mice showed severe liver damage, cellular infiltration, tissue necrosis, and decreased antioxidant capacity. In contrast, intragastric administration of MEPs showed hepatoprotective effects against DSS-induced liver injury. MEPs remarkably elevated the expression levels of superoxide dismutase, glutathione peroxidase, and catalase. Additionally, it decreased malondialdehyde and myeloperoxidase levels in the liver. These results indicate that the protective effects of MEP against DSS-induced hepatic injury could rely on its ability to reduce oxidative stress, suppress inflammatory responses, and improve antioxidant enzyme activity in the liver. Therefore, MEPs could be explored as potential natural antioxidant agents in medicine or as functional foods to prevent liver injury.Keywords:Morchella esculenta;polysaccharide;antioxidant;ulcerative colitis;oxidative stress
研究领域:
药理学
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营养学
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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
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Jingwen Xiao,Shilin Zhou,Fengshu Fei,Lin Long,Chuanlong Guo
Ulcerative colitis (UC) is a persistent intestinal disorder featuring periodic flare-ups of the colon's inner lining inflammation. Current therapeutic strategies, while effective in managing symptoms, are often limited by side effects and high costs. This study investigates the potential of pectin-loaded ferulic acid (PC-FA) nanoparticles as a novel therapeutic approach for UC, focusing on their ability to modulate the cGAS-STING pathway, a key mediator in the inflammation associated with UC. PC-FA nanoparticles were prepared and characterized for their physicochemical properties, antioxidant capacity, biocompatibility, and influence on the cGAS-STING pathway. In vitro experiments demonstrated that PC-FA nanoparticles enhanced the solubility and bioavailability of ferulic acid (FA), reduced oxidative stress, and protected colon epithelial cells from damage caused by the administration of dextran sulfate sodium (DSS). In vivo studies in a DSS-induced colitis mouse model showed that PC-FA nanoparticles mitigated weight reduction, lowered disease activity index (DAI) scores, and sustained colon length, and ameliorated histopathological changes. Additionally, PC-FA nanoparticles effectively targeted DNA damage and inhibited the cGAS-STING pathway, leading to a significant reduction in pro-inflammatory cytokines. Pharmacokinetic studies revealed rapid absorption of PC-FA in the bloodstream, with a predominant distribution in the intestines. The study concludes that PC-FA nanoparticles are a promising therapeutic strategy for UC, offering targeted drug delivery, enhanced bioavailability, and anti-inflammatory effects.
研究领域:
药理学
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免疫学
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消化系统疾病
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DOI
PubMed
高影响因子
Nanomedicine
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2025
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IF 3.9
Dan Zhang,Beiwei Zhu,Yu Xu,Fengxian Luo,Tao Chen,Lihang Chen,Xinchuang Wang,Di Wu,Jiangning Hu
Aim This study aims to develop and assess the therapeutic potential of oleanolic acid nanoparticles (OA NPs) in treating ulcerative colitis (UC).Materials & methods OA NPs were synthesized using an emulsion solvent evaporation method, forming spherical nanoparticles with an average diameter of 138.1 nm. The nanoparticles were designed to target the colon through the enhanced permeability and retention (EPR) effect. Network pharmacology and molecular docking identified key inflammatory pathways, and in vitro (RAW264.7 cells) and in vivo (DSS-induced UC mouse model) experiments evaluated their anti-inflammatory effects and therapeutic efficacy.Results OA NPs successfully targeted the colon and demonstrated improved bioavailability. In vitro experiments showed that OA NPs reduced oxidative stress and inflammation by downregulating pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and promoting macrophage polarization from M1 to M2. In the DSS-induced UC mouse model, oral administration of OA NPs significantly alleviated colitis symptoms, improved colon length, reduced inflammation, and mitigated tissue damageConclusion OA NPs mitigate UC pathology through targeted delivery, enhanced stability, and modulation of inflammatory pathways, providing a promising approach for UC treatment. Further studies are needed to evaluate their long-term safety and clinical applicability.
研究领域:
药理学
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生物医学工程
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消化病学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xiaofeng Liu,Yong Zhao,Chenyue Liu,Chunying Li,Yan Yi,Suyan Liu,Xuan Tang,Chen Pan,Yushi Zhang,Jingzhuo Tian,Jiayin Han,Xingnan Yue,Aihua Liang
Ethnopharmacological relevance Psoraleae Fructus (PF), the dried mature fruit of the leguminous plant Psoralea corylifolia L., is often used as a nutraceutical and to treat ulcerative colitis (UC). However, recently there have been reports of PF-induced liver injury. Aim of the study To investigate the difference and mechanism of hepatotoxicity between normal and UC rats oral administration with PF, and clarify the relationship between PF risk and disease status. Materials and Methods PF water extracts (at the human equivalent dosage and 8-fold greater; 0.7 and 5.6 g/kg/day, respectively) were given to normal and UC rats for 4 weeks, and the general behaviors and colonic mucosal conditions were observed. The liver injury and its mechanism were studied by blood biochemistry, coagulation time, liver hematoxylin and eosin (H&E) staining, bile acids (BAs) metabolism, transcriptome analysis, quantitative real-time polymerase chain reaction (qRT‒PCR) and western blot (WB)experiments. Results Normal rats receiving 5.6 g/kg PF water extract showed significantly increased serum levels of total bilirubin (TBIL) and total bile acids (TBA), significantly prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboplastin time (TT), and slightly swollen hepatocytes, and obvious hepatobiliary hyperplasia. These liver injuries may be related to disordered BAs metabolism: the levels of farnesoid x receptor (FXR) and sulfotransferase family 2A member 1/2 (SULT2a1/a2) were down-regulated, whereas the levels of microsomal epoxide hydrolase (mEH), organic anion transporting polypeptide (OATP) and multidrug resistance-associated protein 3 (MRP3) were up-regulated, leading to liver and blood UnconBA and GlycineBA accumulation. However, at the same dose, UC model rats exhibited no obvious liver damage. Conclusion Normal rats, but not UC rats, displayed signs of liver injury in response to 5.6 g/kg PF water extract administration. Therefore, we recommend that healthy individuals should be aware of the potential risks associated with PF, and other patients should take PF according to their physician’s guidance.
研究领域:
药理学
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分子生物学
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中医药学
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DOI
PubMed
高影响因子
Foods
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2025
·Vol. 14
·期 13
·2345
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IF 5.1
Yifei Guo,Xinyu Yu,Rongrong He,Jianfei Pei,Haiming Chen,Weijun Chen
Ferulic acid (FA) exhibits beneficial properties in ulcerative colitis (UC) pathogenesis, while sensitivity to the environment and enzymes limits its use in UC therapy. Therefore, this study aims to develop a colon-targeted nanocomplex delivery system using FA and investigate its protective effects and underlying regulatory mechanisms in UC mice. A novel Zein/FA–pectin (PEC)/chitosan (CS) nanocomplex was successfully fabricated in this study. Through systematic adjustment of the PEC/CS-to-Zein/FA ratio, optimal encapsulation efficiency (60.1%) and loading capacity (26.2%) were achieved. The characterized data indicated that hydrogen bonds, electrostatic interactions, and hydrophobic forces were the main driving forces maintaining the formation of the nanocomplexes, accompanied by alterations in the secondary structure of Zein. The Zein/FA–PEC/CS nanocomplexes demonstrated excellent thermal/storage particle size stability and exhibited both protective and sustained-release effects of FA during simulated gastrointestinal digestion. Furthermore, the results demonstrated that the nanocomplexes potentially alleviate UC by regulating inflammatory cytokines, oxidative stress, and gut microbiota. Compared to unencapsulated FA, the nanocomplexes have a better effect on alleviating UC symptoms. In summary, Zein/FA–PEC/CS nanocomplexes have promising prospects in alleviating colitis in UC mice.
研究领域:
生物医学
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药剂学
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食品科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 23
·8140
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IF 4.927
Jianchun Zhao,Wenmin Yuan,Shixiao Wang,Hongwei Zhang,Dan Chen,Xiaochen Niu,Xiaochun Liu,Li Liu,Jiangming Gao
M10, a novel myricetin derivative, is an anti-inflammatory agent designed for treatment of colitis. Here, we aim to investigate its pharmacokinetic behavior and tissue distribution in a mouse model with colitis. Pharmacokinetics and tissue distribution of M10 and its metabolite myricetin were compared in normal mice and in dextran-sodium-sulfate (DSS)-induced colitis mice. The role of fecal microbiota was also analyzed during metabolism of M10 in vitro. After oral administration, M10 was very low in the plasma of both normal and diseased mice. However, both M10 and myricetin were mainly distributed in the gastrointestinal tract, including the stomach, colon and small intestine, in physiological and pathological conditions. Significantly, M10 and myricetin were found in higher levels in gastrointestinal tracts with inflamed tissues than in normal tissues of mice. An in vitro assay revealed that 80% of M10 was metabolized to myricetin via fecal microbiota. After oral administration, M10 was not absorbed into circulation but mainly distributed in the inflamed submucosal tissues of colitic mice, where it was metabolized into myricetin to prevent colitis development.Keywords:M10;myricetin;pharmacokinetics;tissue distribution;ulcerative colitis
研究领域:
药理学
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医学
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肠道微生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Chunru Wang,Junyao Li,Xiangsheng Han,Shuai Liu,Xintao Gao,Chuanlong Guo,Xiaochen Wu
Silk sericin (SS) has become a noticeable drug nanocarrier due to its excellent biocompatibility and bioactivity. To further extend the application of SS, a facile one-step process was constructed to fabricate SS-stabilized-drug composites. Various insoluble drugs can be encapsulated into SS with high loading amount, and showed good dispersity in aqueous solution. For example, proanthocyanidins (PAC), a natural polyphenol with initial antioxidant and anti-inflammatory effects, can be loaded on SS to form SS/PAC composites. The SS/PAC can disperse uniformly in aqueous solution with an average particle diameter of ~136 nm, and showed high drug loading amount of 1767 mg/g. The SS/PAC exhibited high antioxidant efficiency and excellent biocompatibility (non-irritant, non-hemolysis, and non-cytotoxicity), could remarkably alleviate the symptoms of dextran sulfate sodium-induced ulcerative colitis by decreasing the disease activity index scores, inhibiting the shortening of colon length, regulating oxidative stress , suppressing inflammation, and reversing the histopathological injuries. This work provides a simple method to fabricate SS-stabilized-drug composites, promises high potential in therapeutic and pharmaceutical applications .
研究领域:
药理学
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生物材料学
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消化病学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
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2023
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IF 4.6
Chunru Wang,Yingjie Xiang,Wenjie Ma,Chuanlong Guo,Xiaochen Wu
Ulcerative colitis is a chronic inflammatory bowel disease with a high recurrence rate. Natural phytochemical compounds are increasingly being considered as preventative and supportive treatments for this condition. However, the poor water solubility and stability of many of these compounds limit their effectiveness in vivo. To address this issue, fisetin (FT), a natural phytochemical with poor solubility, was stabilized using silk sericin (SS) to create a composite (SS/FT). The therapeutic potential of the SS/FT on ulcerative colitis was extensively investigated, and the results showed that it effectively alleviated the body weight loss and colon length shortening induced by dextran sulfate sodium. Notably, SS/FT downregulated the immune response, decreased colonic histopathological lesions, and reduced the cGAS/STING signal activation. This suggests that SS/FT may offer a promising therapy for treating ulcerative colitis. This article is protected by copyright. All rights reserved
研究领域:
药理学
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炎症性肠病
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天然产物化学
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DOI
PubMed
高影响因子
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