MOLECULES
·
2021
·Vol. 26
·期 21
·6604
·
IF 4.412
Ruige Cao,Xing Wu,Hui Guo,Xin Pan,Rong Huang,Gangqiang Wang,Jikai Liu
Naringin is a kind of multi-source food additive which has been explored broadly for its various biological activities and therapeutic potential. In the present study, the protective effect and mechanism of naringin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated. The results showed that naringin significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), colon length shortening, and colon pathological damage. The tissue and serum secretion of inflammatory cytokines, as well as the oxidative stress, were decreased accordingly upon naringin intervention. Naringin also decreased the proteins involved in inflammation and increased the expression of tight junction (TJ) proteins. Moreover, naringin increased the relative abundance ofFirmicutes/Bacteroidesand reduced the content ofProteobacteriato improve the intestinal flora disorder caused by DSS, which promotes the intestinal health of mice. It was concluded that naringin can significantly ameliorate the pathogenic symptoms of UC through inhibiting inflammatory response and regulating intestinal microbiota, which might be a promising natural therapeutic agent for the dietary treatment of UC and the improvement of intestinal symbiosis.Keywords:ulcerative colitis;naringin;intestinal microbiota;inflammation
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Huanhuan Liu,Chunhong Yan,Yue Teng,Jian Guo,Chencheng Liang,Xiaodong Xia
Background: Inflammatory bowel disease (IBD) is an increasing health burden worldwide. Punicalagin, a bioactive component rich in pomegranate rind, has been shown to attenuate chemical or bacteria-induced experimental colitis in mice, but whether punicalagin exerts its function through modulating gut microbiota and metabolites remains unexplored. Results: Punicalagin (100 mg per kg per day) administered orally to mice alleviated dextran-sodium sulfate (DSS)-induced colitis. Gut microbiota analyzed by 16S rRNA sequencing showed that punicalagin altered gut microbiota by increasing the Lachnospiraceae_NK4A136_group and Bifidobacterium abundance. To evaluate the effect of punicalagin-modulated microbiota and its metabolites in colitis mice, we transplanted fecal microbiota and sterile fecal filtrate (SFF) to mice treated with oral antibiotics. The results of fecal microbiota transplantation (FMT) demonstrated that punicalagin's anti-colitic effect is transferable by transplanting punicalagin-modulated gut microbiota and its metabolites. Additionally, we discovered that punicalagin-modulated sterile fecal filtrate also exhibits anti-colitis effects, as evidenced by improved intestinal barrier integrity and decreased inflammation. Subsequently, fecal metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). The analysis revealed that punicalagin significantly increased the level of D-ribose. In vitro experiments showed that D-ribose has both anti-inflammatory and antioxidant properties. Furthermore, D-ribose significantly mitigated DSS-induced colitis symptoms in mice. Conclusions: Overall, this study demonstrated that gut microbiota and its metabolites partly mediate the protective effect of punicalagin against DSS-induced colitis in mice. D-ribose is a key metabolite that contributes to the anti-colitic effect of punicalagin in mice.
研究领域:
胃肠病学
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微生物学
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药理学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 16
·8703-8716
·
IF 6.317
Cui Cao,Linlin Wang,Chunqing Ai,Guiping Gong,Zhongfu Wang,Linjuan Huang,Shuang Song,Beiwei Zhu
Ulcerative colitis (UC) is often accompanied by the dysbiosis of gut microbiota and metabolism. Our previous study indicated that arabinogalactan from Lycium barbarum (LBP-3) could markedly attenuate the symptoms of chronic UC in mice by modulating the structure of gut microbiota. This study explored the impact of LBP-3 on the fecal metabolomic profiling of the same cohort of mice by HPLC-TripleTOF/MS. Untargeted metabolomic analyses indicated that supplementation with LBP-3 markedly reversed 18 of the 48 differential metabolites (mainly belonging to amino acids and organic acids) disturbed by DSS. Targeted metabolomics revealed that the lower levels of tryptophan, lysine, diiodothyronine, kynurenine, and betaine and higher levels of phenylalanine, leucine, glutamine, isoleucine, homoserine, (S)-2-hydroxyglutarate, 2-isopropylmalic acid, ascorbic acid, gluconic acid, and taurine, which were caused by DSS induction, were reversed by LBP-3 treatment. In addition, pathway analysis showed that the pentose phosphate pathway, phenylalanine metabolism, ascorbate and aldarate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis were strongly affected by LBP-3. More importantly, the above amino acids, organic acids, and metabolic pathways changed by LBP-3 were correlated with the abundance of gut microbiota such as Turicibacter, Lactobacillus, Parasutterella, Odoribacter, Veillonella, Faecalibacterium, and Ruminococcaceae. This study advances our understanding of the interaction between the microbiome and metabolomics in DSS-induced chronic colitis after LBP-3 treatment.
研究领域:
胃肠病学
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微生物学
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代谢组学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Shuang Lu,Kai Na,Jiani Wei,Ting Tao,Li Zhang,Ying Fang,Xiangyu Li,Xiaohua Guo
Alginate oligosaccharides (AOS) are divided by their monomer sequences into three types: oligomannuronate (MAOS), oligoguluronate (GAOS), and heterogeneous AOS (HAOS). However, how these AOS structures differentially regulate health and modulate gut microbiota is unclear. We explored the structure-function relationship of AOS both in an in vivo colitis model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged cell model. We found that MAOS administration significantly alleviated the symptom of experimental colitis and improved the gut barrier function in vivo and in vivo . Nevertheless, HAOS and GAOS were less effective than MAOS. The abundance and diversity of gut microbiota are obviously increased by MAOS intervention, but not by HAOS or GAOS. Importantly, microbiota from MAOS-dosed mice through FMT decreased the disease index level, alleviated histopathological changes, and improved gut barrier function in the colitis model. Super FMT donors induced by MAOS but not by HAOS or GAOS, seemed to exert potential in colitis bacteriotherapy. These findings may aid in establishing precise pharmaceutical applications based on the targeted production of AOS.
研究领域:
药理学
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胃肠病学
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微生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Tian Tang,Ying Zhang,Xinrui Xing,Ruiqi Sun,Zhe Yu,Yuan Tian,Zunjian Zhang,Pei Zhang,Fengguo Xu
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder with an increasing incidence worldwide. Due to the complex and unclear therapeutic targets, unmet UC therapeutic drugs still exist. Recently, acylcarnitine metabolism disorder has been linked to intestinal inflammation, but its role in UC remains elusive. According to our preliminary non-targeted metabolomics data, acylcarnitines (ACs) was screened as the disturbed metabolites in the different intestinal inflammation-related diseases. Here we quantified 26 ACs within liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the dextran sulfate sodium (DSS)-induced UC rat model, and found that long-chain acylcarnitines (LCACs) were increased to varying degrees. As the key metabolites of fatty acid β-oxidation (FAO), the upstream metabolites long-chain fatty acids (LCFAs) and the related metabolic enzymes were further characterized, the results showed that the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A)-mediated LCFAs-LCACs metabolic axis was activated sharply. Next in vitro experiments exhibited that CPT1A was significantly upregulated in both inflammatory macrophages and colonic epithelial cells, and inhibition or knockdown of CPT1A could reduce the inflammation level remarkably. Thus, we screened the pharmacologic inhibitors of CPT1A from FDA approved drugs, within molecular docking, Western blot and cell membrane chromatography (CMC) technology, gliquidone was found to inhibit CPT1A in a dose-dependent manner and exert anti-inflammatory effects in vitro . Animal experiments also showed that gliquidone alleviated DSS-induced UC significantly. In summary, our study presents that within metabolomics analysis, inhibiting CPT1A is focused to be a potential therapeutic strategy against UC, and gliquidone represents an alternative treatment.
研究领域:
代谢组学
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炎症性肠病
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药理学
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分子生物学
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胃肠病学
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药物研发
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Functional Foods
·
2023
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IF 5.6
Chao Nie,Yunyi Zhao,Pengjie Wang,Ran Wang,Yixuan Li,Xifan Wang,Bing Fang,Xiaoyu Wang,Jing Zhan,Longjiao Zhu,Chong Chen,Weibo Zhang,Haiping Liao,Rong Liu
Momordica Charantia Polysaccharide (MCP), the main active ingredient of M. charantia, exhibits multiple pharmacological properties. However, its effects and mechanisms against ulcerative colitis (UC) remain unclear. In this study, we employed a dextran sulfate sodium (DSS)-induced experimental colitis model to investigate the therapeutic potential of MCP. Our results revealed that prophylactic MCP dramatically attenuated the pathological symptoms associated with colitis in mice, including body weight loss, reduction in colon length, and tissue damage. Moreover, we found prophylactic MCP reduced DSS-induced intestinal permeability and enhanced intestinal barrier integrity. Notably, we observe that prophylactic MCP restored the diversity and richness of the gut microbiota, thereby ameliorating gut microbiota dysbiosis in DSS-induced mice models. Furthermore, fecal microbiota transplantation (FMT) experiments demonstrated that the microbiota derived from MCP-dosed mice remarkably alleviated colitis symptoms. Collectively, our study provided valuable insights into the potential of MCP as a promising prebiotic agent for maintaining intestinal health, and demonstrated that MCP ameliorated colitis in a gut microbiota-dependent manner.
研究领域:
药理学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Yiren Yang,Yuwei Zhang,Jiangping Song,Yaqian Li,Liuyang Zhou,Hongtao Xu,Kaizhang Wu,Jie Gao,Mouming Zhao,Yang Zheng
This study aimed to explore the efficacy of polysaccharides from bergamot (BP) in alleviating DSS-induced colitis. Results showed that BP was primarily composed of two components, BP-1 and BP-2, with similar monosaccharide compositions to BP (mainly glucose and xylose) and molecular weights (Mw) of 4.50 × 10 5 and 2.35 × 10 5 Da. This study found BP relieved disease symptoms such as weight loss and colon shortening in mice with colitis. Gut microbiota and metabolomics analysis revealed that the BP could also promote the proliferation of beneficial bacteria such as Bifidobacteria , Butyrivibrio , and Blautia , resulting in increased levels of SCFAs and L -phenylalanine, which were associated with phenylalanine , tyrosine , and tryptophan metabolism pathways. Further analysis validated the inflammatory activity of L -phenylalanine. Hence, BP may relieve colitis symptoms by regulating the gut microbiota and metabolism, which reduced inflammation and enhanced the expression of tight junctional proteins (TJ proteins) and mucin in the intestine.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-17
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IF 4.8
Su Qiyuan,Hu Qian,Wu Songtao,Yang Suqin,Su Hanwen,Zhang Zhengjun,Ling Chengxiu
This study aimed to evaluate the therapeutic properties of the traditional Chinese medicine Xuesanqi (XSQ, from the rhizome of Polygonum amplexicaule D. Don) in treating ulcerative colitis. We hypothesized that its many active components can alleviate symptoms of colitis by regulating the gut microbiota, its metabolites, and various signaling pathways. To test our hypotheses, we designed a DSS- induced colitis model in C57BL/6 male mice. Apparent metrics were evaluated in each group of mice and performed histological analysis of relevant tissues. The gut microbial composition was analyzed by 16S rRNA sequencing of bacteria. Simultaneously, the SCFAs content was detected by gas chromatography, inflammatory factor secretion was evaluated by ELISA or western-blot, the expression of tight junction protein and key proteins of the MAPK signaling pathway were analyzed by western-blot. Our result showed that the treatment with XSQ alleviated significant various symptoms such as weight loss, blood in stool, and shortening of colon. In addition, XSQ treatment restored the dysregulated gut microbiota in colitis mice, increased short chain fatty acids (SCFAs) and normalized the MAPK/ERK/JNK signaling pathways, promoted expression of tight junction protein Occludin, Claudin-1, and E-cadherin proteins. Furthermore, we also observed a dose-dependent pattern in these treatment responses. These findings demonstrated the active components of XSQ is a promising new treatment platform for ulcerative colitis. Graphical
研究领域:
药理学
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胃肠病学
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微生物学
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免疫学
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传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Mingjun,Feng Yang,Luo Dan,Zhang Chen,Zhou Jing,Dai Hengheng,Lin Mingxiong,Tong ZhanQi
Purpose: Wuwei Kushen Changrong capsule (Composite Sophora Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.Methods: The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.Results: CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4/JNK1/STAT3 activation pathway, consequently suppressing the STAT3/NLRP3/IL-1β pathway and inhibiting the production of inflammatory factors such as IL-17A.Conclusion: The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC’s anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.
研究领域:
药理学
·
免疫学
·
胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Menglin Chen,Hong Yao,Huizi Tan,Wenqi Huang,Quanyong Wu,Shaoping Nie
Most scientific investigations regarding inflammatory bowel disease (IBD) pathogenesis or therapeutic strategies use dextran sulfate sodium (DSS)-induced models performed on mice. However, differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials. In this study, the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota. Disorders in disease activity index (DAI), morphology and histology of colon tissue, intestinal permeability, and secretion of MPO, TNF-α and IL-6 were ameliorated by daily intake of live B. longum NSP001 cells in both conventional and humanised colitis mice. But the abnormal thymus index, and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B. longum NSP001 and humanised microbiome. The accumulation of acetic acid and propionic acid in colon microbiome, and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B. longum NSP001. These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.
研究领域:
炎症性肠病
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微生物组
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益生菌
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治疗策略
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动物模型
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人源化模型
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Guohui Xue,Huifang Xiong,Shixiu Wang,Yingjun Fu,Yong Xie
Objective Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. Methods Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. Results The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. Conclusion Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. Data availability All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.
研究领域:
药学
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药理学
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免疫学
·
药物递送系统
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炎症性肠病
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man
Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.
研究领域:
免疫学
·
胃肠病学
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微生物学
·
药理学
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营养学
✓ 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）