Nutrients
·
2026
·Vol. 18
·期 18
·2975
·
IF 5.8
Hang Zhou,Qun Shen,Liyang Wu,Zhihao Ma,Xin Ren,Jilite Wang,Zhihui Hao,Qingyu Zhao
Background:The incidence of ulcerative colitis (UC) continues to rise, and food-derived bioactive peptides have attracted increasing attention as potential nutritional interventions for intestinal inflammation. This study investigated the preventive effects of the adzuki bean-derived peptide IFNNDPNNHP (IP10 peptide) on dextran sulfate sodium (DSS)-induced acute colitis in mice and explored the involvement of the gut microbiota.Methods:Mice received prophylactic IP10 peptide at 100 or 200 mg·kg−1. Colitis severity was assessed based on body weight, disease activity index, colon length, histopathology, and inflammatory cytokine levels. Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to further evaluate the role of the gut microbiota.Results:Prophylactic IP10 peptide administration attenuated DSS-induced colitis, with the 200 mg·kg−1dose more effectively attenuating body weight loss and colon shortening, reducing disease activity index scores, and modulating inflammatory cytokine levels. IP10 peptide increased microbial richness and diversity, decreased the relative abundance ofEscherichia-Shigella, and increased the relative abundances of SCFA-associated taxa, includingnorank_f__MuribaculaceaeandLachnospiraceae_NK4A136_group. It also increased fecal SCFA levels, particularly acetate and butyrate; the high dose additionally restored propionate and valerate. When the gut microbiota was depleted using antibiotics, the protective effects of the IP10 peptide were no longer detectable, whereas FMT using fecal microbiota from donors receiving the high dose of IP10 peptide attenuated colitis and increased fecal SCFA levels in recipient mice.Conclusions:IP10 peptide alleviates DSS-induced acute colitis, and this effect may be partly associated with alterations in the gut microbiota, including the enrichment of SCFA-associated taxa and increased fecal SCFA levels. These findings support its potential as a functional food ingredient for intestinal health.
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DOI
高影响因子
GENETICS AND MOLECULAR RESEARCH
·
2015
·
IF 0.775
C-P Li,J-H Li,S-Y He,O Chen,L Shi
The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.
研究领域:
药理学
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免疫学
·
胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Yuanyuan Gou,Zichen Wang,Liping Zhou,Jinpan Du,Jiaxin Huang,Jing Li,Xuyu Zhang,Su Guan
Inflammatory bowel disease is a relapsing inflammatory disease seriously endanger human health. Wedelolactone (WED) is a major active ingredient from Eclipta prostrata (L.) L. and has shown anti-inflammatory effects. However, the mechanism of WED in treating inflammatory colitis remains unknown. We aimed to investigate the mechanisms of WED in treating ulcerative colitis through lipidomic study. Sixty male C57BL/6 mice were exposed to DSS to induce acute colitis. Disease progression was judged by the disease activity index (DAI) and pathological changes of colon tissue. An ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was performed for colon and plasma lipidomics analyses. Differential metabolites in the three groups were distinguished by univariate and multivariate analysis. WED exerted anti-inflammatory effects representing by body weight and DAI score. Three metabolites were identified in plasma and 20 in colon. According to pathway analysis, the effects of WED on colitis were associated with seven pathways. The glycerophospholipid metabolism and ether lipid metabolism were the primary pathways. The findings provide important insight of the mechanism of WED in treating DSS induced colitis through lipidomic perspective.
研究领域:
药理学
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炎症性肠病研究
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代谢组学
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DOI
PubMed
高影响因子
Science China-Life Sciences
·
2024
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IF 8
Zhang Yinghui,Liu Yadan,Jiang Bing,Chen Lifan,Hu Jie,Niu Buying,Chang Jie,Fan Zisheng,Zhou Jingyi,Wang Yajie,Teng Dan,Ma Ning,Wang Xiaofeng,Yang Ruirui,Zheng Mingyue,Zhang Sulin
The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges. The activation of STING is a multi-step process that includes binding with cGAMP, self-oligomerization, and translocation from the endoplasmic reticulum to the Golgi apparatus, ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines. It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation. Traditional structure-based drug screening methodologies generally focus on specific binding sites. In this study, a TransformerCPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein. The natural product Licochalcone D (LicoD) is identified as a potent and selective STING inhibitor. LicoD does not bind to the classical ligand-binding pocket; instead, it covalently modifies the Cys148 residue of STING. This modification inhibits STING oligomerization, consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB. LicoD treatment ameliorates the inflammatory phenotype in Trex1 −1− mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer (CAC). In summary, this study reveals the potential of LicoD in treating STING-driven inflammatory diseases. It also demonstrates the utility of the TransformerCPI model in discovering allosteric compounds beyond the conventional binding pockets.
研究领域:
免疫学
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药理学
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分子生物学
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炎症
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药物发现
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产品关联
DOI
PubMed
高影响因子
Drug Discoveries and Therapeutics
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2025
·
IF 1.5
Fangzhou Dou,Shasha Hu,Daoran Lu,Jianjun Gao
Chronic inflammation in the colon has been recognized as a key pathogenic mechanism driving colorectal cancer development. TRPA1 (transient receptor potential ankyrin 1), a key member of the TRP cation channel superfamily, is closely implicated in inflammatory processes and has emerged as a promising therapeutic target for anti-inflammatory drug development. However, the precise role of TRPA1 in colorectal carcinogenesis and its potential as a therapeutic target for colorectal cancer (CRC) remain incompletely understood. In this study, we demonstrate that Trpa1 knockout significantly exacerbates DSS-induced colitis-associated tumorigenesis in murine models, a phenomenon mechanistically linked to Trpa1 deficiency-mediated aggravation of inflammatory bowel pathology. RNAseq and gene knockout effect analysis revealed a consistently low expression pattern of TRPA1 across colorectal cancer cell lines (n = 58, median log2(TPM+1) = 0.025), with limited impact on cell viability upon TRPA1 knockout. Notably, analysis of human clinical specimens revealed substantial downregulation of TRPA1 expression in CRC compared to adjacent normal tissues. Kaplan-Meier survival analysis further indicated that patients with TRPA1-low tumors exhibited significantly poorer overall survival outcomes. These collective data suggest a tumor-suppressive role for TRPA1 in colorectal carcinogenesis, potentially through its immunomodulatory functions within the colitis-cancer transformation axis.
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Ruping Shan,Kexin Wang,Qiujie Chen,Lijuan Bao,Keyi Wu,Yihong Zhao,Yu Han,Yating Gao,Naisheng Zhang,Xiaoyu Hu,Yunhe Fu,Caijun Zhao,Wenchao Bian
Inflammatory bowel disease is becoming increasingly prevalent and represents a major concern in global public health. However, conventional therapies often come with various adverse effects. Phytosphingosine (PS), a key metabolite in sphingolipid metabolism, is widely found in plants and fungi and possesses notable anti-inflammatory properties. In this study, we aimed to evaluate the protective effects of PS against dextran sulfate sodium (DSS)-induced experimental colitis in mice and elucidate its underlying mechanisms. Our results showed that oral administration of PS significantly alleviated DSS-induced colonic injury and reduced levels of proinflammatory cytokines such as TNF-α and IL-1β. Additionally, PS improved intestinal barrier function disrupted by DSS, as indicated by increased expression of mucin-2 and tight junction proteins. Furthermore, PS suppressed the activation of the NF-κB signaling pathway, oxidative stress and enhanced PPARγ expression. We also observed that PS mitigated DSS-induced gut dysbiosis in mice, characterized by an increase in Bacteroidota and a decrease in Proteobacteria . To explore the role of the gut microbiota in PS-mediated protection against colitis, fecal microbiota transplantation (FMT) was conducted in DSS-treated mice. Recipients of FMT from PS-treated donors exhibited reduced inflammatory responses and improved intestinal integrity, accompanied by a higher abundance of Bacteroidota in the gut. Additionally, PS treatment modified the profile of short-chain fatty acids in the mice, with a notable increase in the levels of butyrate and propionate. Overall, our findings demonstrate that PS attenuates DSS-induced colitis in mice through modulation of the gut microbiota, providing a potential strategy for IBD intervention via microbiota regulation.
研究领域:
免疫学
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消化病学
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分子生物学
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微生物组学
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炎症与免疫
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药理学
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转化医学
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DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 11
·2098
·
IF 7.675
Na Wang,Weixuan Chen,Chenxu Cui,Yuru Zheng,Qiuying Yu,Hongtao Ren,Zhigang Liu,Chao Xu,Gaiping Zhang
Polyphenols from peanut skin have been reported to possess many beneficial functions for human health, including anti-oxidative, antibacterial, anticancer, and other activities. To date, however, its anti-inflammatory effect and the underlying mechanism remain unclear. In this study, the anti-inflammatory effect of peanut skin procyanidins extract (PSPE) and peanut skin procyanidins (PSPc) were investigated by a dextran sodium sulfate (DSS)-induced colitis mouse model. The results showed that both PSPE and PSPc supplementation reversed the DSS-induced body weight loss and reduced disease activity index (DAI) values, accompanied by enhanced goblet cell numbers and tight junction protein claudin-1 expression in the colon. PSPE and PSPc treatment also suppressed the inflammatory responses and oxidative stress in the colon by down-regulating IL-1β, TNF-α, and MDA expressions. Meanwhile, PSPE and PSPc significantly altered the gut microbiota composition by increasing the relative abundance ofClostridium XlVbandAnaerotruncus, and inhibiting the relative abundance ofAlistipesat the genus level. PSPE and PSPc also significantly elevated the production of short-chain fatty acids (SCFAs) in mice with colitis. The correlation analysis suggested that the protective effects of PSPE and PSPc on colitis might be related to the alteration of gut microbiota composition and the formation of SCFAs. In conclusion, the current research indicates that supplementation of PSPE and PSPc could be a promising nutritional strategy for colitis prevention and treatment.Keywords:peanut skin;procyanidins;DSS-induced;ulcerative colitis
研究领域:
营养学
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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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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Qianyun Chen,Xueyun Duan,Heng Fan,Meng Xu,Qing Tang,Lijuan Zhang,Zhexing Shou,Xingxing Liu,Dongmei Zuo,Jia Yang,Shuangjiao Deng,Yalan Dong,Hui Wu,Yujin Liu,Zhen Nan
Oxymatrine (OMT), an alkaloid derived from the root of the Sophora flavescens , has been reported to possess a significant effect on relieving UC owing to its anti-inflammatory property. But the other therapeutic mechanism of OMT remains unclear. Recent studies have found, PI3K/AKT signaling pathway is involved in the pathogenesis of UC by pro-inflammatory effects and activating T cells . Moreover, PI3K/AKT pathway is one of the most important pathways for regulating cell apoptosis . Thus, we aim to explore whether OMT protects against UC by targeting PI3K/AKT pathway. We established the UC mice models, using LY294002 (a specific inhibitor of PI3K/AKT) as a positive control, to observe the effect of low, medium and high dose of OMT on UC and its influence on PI3K/AKT signaling pathway. Our data indicated that OMT can significantly ameliorate UC through anti-inflammatory, pro-apoptotic, down-regulating the differentiation of Th1 and Th17 cells via PI3K/AKT pathway. This study reveals that PI3K/AKT signaling pathway is a potential mechanism of OMT-induced UC remission and suggests that OMT is a promising therapeutic agent for the treatment of UC.
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
Food & Function
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2023
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IF 6.1
Zi-han Wang,Guang-yao Zhang,Cong Sun,Shu-Xin Ning,Da-Yong Zhou,Liang Song
The pursuit for food-based alternatives to conventional therapies for ulcerative colitis (UC) demands immediate attention. In prior investigations, we synthesized WPI-stachyose conjugates through the Maillard reaction, identifying them as functional prebiotics. However, their impact on in vivo regulation of gut microbiota remains inadequately explored. To bridge this gap, we delved into the therapeutic effects and mechanisms of WPI-stachyose conjugates as prebiotic-functional components in C57BL/6J mice afflicted with Dextran Sodium Sulfate (DSS)-induced UC. Treatment involving WPI-stachyose conjugates led to significant therapeutic advancements, evident in the reduction of pro-inflammatory cytokine levels and restoration of gut microbiota composition. Noticeable enhancements were observed in UC-associated symptoms, including weight loss, colon length reduction, and tissue damage, notably improving in the treated mice. Remarkably, both the conjugates and the physical combination effectively lowered pro-inflammatory cytokines and oxidative stress, with the conjugates demonstrating enhanced effectiveness. Furthermore, the simultaneous administration of WPI-stachyose conjugates further amplified the presence of beneficial bacteria and elevated short-chain fatty acids, acknowledged for their favorable impact across various conditions. These findings underscore the potential therapeutic application of WPI-stachyose conjugates in addressing DSS-induced UC, offering insights into innovative therapeutic strategies.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Ji Yang,Peng Guo,Hongtao Luo,Xin Tang,Wei Liu,Xiaolin Ren
Background: Current therapeutic options for inflammatory bowel disease (IBD) remain suboptimal due to limited efficacy, significant side effects, and high relapse rates, necessitating novel treatment strategies. Lumefantrine, a clinically established antimalarial drug, emerges as a compelling repurposing candidate based on its putative anti-inflammatory activity, though its efficacy and mechanism in IBD remain unexplored.Methods: A murine IBD model was induced by 3% dextran sulfate sodium (DSS). Mice received oral Lumefantrine (20 mg/kg/day) for 7 days. Disease progression was monitored via disease activity index (DAI) scoring and histological analysis. Serum cytokines (IL-1β, IL-6, TNF-α) and colonic inflammatory mediators (Cox-2, iNos) were quantified by ELISA and qPCR. Tight junction proteins (Claudin-1, ZO-1) were assessed by immunohistochemistry and Western blot. Molecular targets were identified through computational docking and pull-down assays. Additionally, NF-κB signaling modulation was assessed in lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IEC-6 and NCM460) via Western blot analysis.Results: Oral administration of Lumefantrine significantly attenuated disease activity index (DAI) scores and restored intestinal barrier integrity through upregulation of epithelial tight junction proteins Claudin-1 and ZO-1. Treated mice exhibited reduced serum levels of IL-1β, IL-6 and TNF-α, along with decreased colonic expression of inflammatory mediators cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos). Computational and experimental approaches identified FLI-1 a transcription factor upregulated in IBD colon tissues as Lumefantrine’s direct binding target. This interaction mediated suppression of NF-κB signaling, specifically downregulating phosphorylation of IκBα and p65 in LPS-stimulated intestinal epithelial cells.Conclusion: Lumefantrine ameliorates experimental colitis through FLI-1-dependent inhibition of the NF-κB pathway, demonstrating high repurposing potential as an IBD therapeutic.
研究领域:
免疫学
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分子生物学
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药理学
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转化医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2025
·Vol. 136
·期 5
·
IF 3.2
Li Xiaofang,He Ningning,Wang Haoyu,Wu Zhinan,Wang Mengmeng,Liang Hewei,Xiao Liang,Yang Zizhen,Li Cunyin,Xu Ping,Dai Tong,Li Shangyong,Zou Yuanqiang
AimsThis study explores the impact of Faecalibacterium longum CM04-06 on inflammatory bowel disease (IBD) by regulating gut microbiota in mice.Methods and resultsWe reanalyzed the distribution of the CM04-06 genome in the metagenome of the IBD cohort and observed a significantly higher abundance of CM04-06 in healthy individuals compared to patients with UC or CD. The prophylactic administration of CM04-06 was evaluated for its effects on intestinal microbial diversity and community composition after a two-week trial in mice. The intestinal microbiota was characterized using metagenomic sequencing of fecal samples on the DNBSEQ platform. CM04-06 treatment resulted in a significant reduction in the Disease Activity Index (DAI) and histological scores, as well as a decrease in the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in both the colon and serum of DSS-induced mice. Furthermore, supplementation with CM04-06 significantly reduced the levels of pro-inflammatory cytokines in both the colon and serum. Additionally, CM04-06 enhanced the integrity of the intestinal epithelial barrier by increasing the expression of tight junction proteins and mucin. Moreover, we observed greater abundances of Faecalibaculum rodentium, Alistipes onderdonkii, Alistipes shahii, and Bifidobacterium animalis after CM04-06 treatment.ConclusionsCM04-06 prevents and alleviates intestinal inflammation by modulating the composition of the microbiota community, increasing the abundance of beneficial probiotics, and suppressing pro-inflammatory cytokine levels.
研究领域:
医学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Xuefeng Li,Huixia Lv,Fanli Shi,Jie Song,Zhenhai Zhang
In this study, high-substituted hydroxypropyl cellulose (HHPC) and low-substituted hydroxypropyl cellulose (LHPC) were orally administered (150 or 300 mg/kg) to investigate the inflammation inhibitory effects on DSS-induced colitis mice. In addition, the anti-inflammatory potential of HHPC in-vitro (RAW 264.7 cells) was evaluated. The result showed that HHPC could inhibit the excessive secretion of TNF-α, IL-6, and NO in RAW 264.7 cells induced by lipopolysaccharide . Oral administration of HHPC and LHPC could dose-dependently mitigate the pathological damage of colon tissue, suppressed spleen edema, preserved thymus index, reduced the serum level of inflammatory mediators (TNF-α, IL-6, IL-1β, and MPO), increased the secretion of sIgA in the colon, and restored the balance of the intestinal flora such as Rikenellaceae_RC9_gut_group, Lachnospiraceae_UCG-006, and Blautia . Overall, this study elucidated the therapeutic potential of LHPC and HHPC as a prebiotic to treat acute ulcerative colitis.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
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