Food & Function
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2024
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IF 5.1
Zhiyuan Lin,Weidong Dai,Shanshan Hu,Dan Chen,Han Yan,Liang Zeng,Zhi Lin
Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg·kg-1-day-1. Chemical composition analysis showed that the levels of 50 com-pounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3”-O-methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.
研究领域:
药理学
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微生物学
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营养学
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胃肠病学
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DOI
PubMed
高影响因子
Nutrients
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2022
·Vol. 14
·期 13
·2765
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IF 6.706
Xuejiao Zhang,Bowei Zhang,Bo Peng,Jin Wang,Yaozhong Hu,Ruican Wang,Shuo Wang
Sugar reduction and sugar control are advocated and gaining popularity around the world. Sucrose, as the widely consumed ingredient in our daily diet, has been reported a relation to gastrointestinal diseases. However, the role of sucrose in inflammatory bowel disease remains controversial. Hence, our study aimed to elucidate the potential role of three doses of sucrose on DSS-induced colitis in C57BL/6 mice and the underlying mechanisms. The results showed that low-dose sucrose intervention alleviated colitis in mice, reducing the expression of inflammatory cytokines and repairing mucosal damages. In contrast, high-dose sucrose intervention exacerbated colitis. Furthermore, three doses of sucrose administration markedly altered gut microbiota composition. Notably, the low-dose sucrose restored microbial dysfunction and enhanced the production of short chain fatty acids (SCFAs). Specifically, the abundance of SCFAs-producing bacteriaFaecalibaculum,Bacteroides,andRomboutsiawere increased significantly in the LOW group. Consistently, PPAR-γ, activated by SCFAs, was elevated in the LOW group, thereby inhibiting the MAPK/NF-κB pathway. Together, our study demonstrates the differential effects of sucrose on colitis at different doses, providing a scientific basis for measuring and modifying the safe intake level of sugar and providing favorable evidence for implementing sugar reduction policies.Keywords:sucrose;gut microbiota;SCFAs;PPAR-γ;MAPK/NF-κB
研究领域:
胃肠病学
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免疫学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Liwei Xue,Xiaosheng Jin,Tingting Ji,Rongzhou Li,Xiaoju Zhuge,Fang Xu,Zijiao Quan,Haibin Tong,Weilai Yu
Objectives Luteolin, known for its multifaceted therapeutic properties against inflammatory diseases, holds potential for addressing the unmet need for effective treatments in ulcerative colitis (UC), a prevalent subtype of inflammatory bowel disease (IBD). This study aimed to comprehensively assess luteolin's therapeutic efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model, shedding light on its anti-UC mechanisms. Methods Our investigation encompassed in vivo assessments of luteolin's therapeutic potential against DSS-induced colitis through rigorous histopathological examination and biochemical analyses. Furthermore, we scrutinized luteolin's anti-inflammatory prowess in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Additionally, we quantitatively evaluated the impact of luteolin on C–C motif chemokine ligand 2 (CCL2)-induced macrophage migration employing Transwell and Zigmond chambers. Furthermore, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and molecular docking were employed to identify potential therapeutic targets of luteolin and investigate their binding sites and interaction patterns. Results Luteolin demonstrated therapeutic potential against DSS-induced colitis by ameliorating colitis symptoms, restoring intestinal barrier integrity, and inhibiting proinflammatory cytokine production in the colonic tissues. Moreover, luteolin demonstrated robust anti-inflammatory activity in vitro , in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Notably, luteolin suppressed the phosphorylation of IKKα/β, IκBα, and p65, along with preventing IκBα degradation in LPS-treated RAW264.7 cells and peritoneal macrophages. Furthermore, luteolin impaired the migratory behavior of RAW264.7 cells and peritoneal macrophages, as evidenced by reduced migration distance and velocity of luteolin-treated macrophages. Mechanistically, luteolin was found to antagonize IKKα/β, subsequently inhibiting IKKα/β phosphorylation and the activation of NF-κB signaling. Conclusion Luteolin emerges as a promising lead compound for the clinical therapy of colitis by virtue of its ability to ameliorate DSS-induced colitis, antagonize IKKα/β, suppress NF-κB signaling, and impede macrophage activation and migration.
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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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Xiaogan Zhao,Tao Lin,Wenkai Jiang,Yihan Lin,Luyao Xiao,Yufang Tian,Kai Ma,Changliang Zhang,Feng Ji,Ghahvechi Chaeipeima Mahsa,Xin Rui,Wei Li
Lactobacillus helveticus LZ-R-5 (R-5), a strain with high epithelial adhesion and bioactive exopolysaccharide production, was isolated from Tibetan kefir grains. This study investigated its potential to alleviate intestinal inflammation using a DSS-induced colitis model in BALB/c mice. We integrated microbial diversity and serological analyses to assess changes in gut flora and cytokines following the R-5 treatment. Pathological assessments showed that R-5 reduced crypt distortion in the proximal colon and mitigated hepatic immune challenges by enhancing gut barrier function. The increased relative expression of TGF-β1 and the downregulation of NLRP3-related inflammatory factors were conducive to preventing organ damage in the thymus and spleen of mice with colitis. Additionally, R-5 stimulated GPR43 expression and improved epithelial nutrition, promoting mucin production to prevent enterotoxin leakage. It also modulated the gut microbiota by suppressing Bacteroides and Erysipelatoclostridium, leading to a microbiota composition more akin to that of normal flora.
研究领域:
微生物学
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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
Food Bioscience
·
2025
·
IF 5.9
Nan Cui,Chongwei Yu,Feiwei Cao,Qinchao Ding,Huiling Pan,Yaqi Zeng,Daxi Ren
Inflammatory bowel disease (IBD) is a prevalent intestinal disorder that profoundly affects human and animal health. Emerging evidence highlights the therapeutic potential of lactic acid bacteria (LAB) in mitigating gastrointestinal pathologies. Prior studies have shown that Lactobacillus helveticus ZJUIDS18 exhibits favorable in vitro growth characteristics, and has the potential to alleviate colitis. This study aimed to investigate the therapeutic effect and mechanism of L. helveticus ZJUIDS18 on mice colitis induced by sodium dextran sulfate (DSS). Key findings demonstrated that L. helveticus ZJUIDS18 intervention can effectively alleviate the symptoms of colitis induced by DSS in mice, including inhibiting the weight loss, colon shortening, and reducing disease activity index score as well as colonic tissue lesions. It increased the expression of tight junction proteins (ZO-1, claudin-1, and occludin) and mucin (MUC2) in colon tissue and decreased the level of myeloperoxidase (MPO), malondialdehyde (MDA), and pro-inflammatory factors IL-6 in colon tissue. Moreover, L. helveticus ZJUIDS18 intervention restored intestinal dysbiosis by down-regulating the relative abundance of harmful genera, namely Parabacteroides, Escherichia-Shigella, and Bacteroides and up-regulating the relative abundance of Bifidobacterium and Erysipelotrichaceae_uncultured. It also significantly increased the content of short-chain fatty acids, including acetic acid and propionic acid. Metabolic profiling further identified the tryptophan metabolism pathway as a critical mediator of the strain's anti-inflammatory effects, with L. helveticus ZJUIDS18 effectively ameliorating DSS-induced metabolic dysregulation. In summary, L. helveticus ZJUIDS18 could be as a probiotic candidate for developing targeted therapeutic strategies against IBD.
研究领域:
微生物学
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胃肠病学
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免疫学
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代谢组学
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益生菌研究
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产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2024
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IF 6.8
Qian-Wen Zhang,Meng-Jiao Yang,Chun-Yu Liao,Reham Taha,Qing-Yu Li,Mohammed Ismail Abdelmotalab,Si-Yu Zhao,Yan Xu,Zhen-Zhou Jiang,Cheng-Han Chu,Xin Huang,Chun-Hua Jiao,Li-Xin Sun
Background and Purpose Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study. Experimental Approach PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis. Key Results PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance. Conclusion and Implications Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Jingjing Li,Suiyuan Ren,Meng Li,Jingai Bi,Guang Yang,Erguang Li
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
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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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
·
IF 3.8
Jia-Nan Yan,Yu-Qiao Wang,Lin Li,Zhu-Jun Zhang,Ling-Yi Gao,Bin Lai,Ce Wang,Li-Chao Zhang,Hai-Tao Wu
Scallop ( Patinopecten yessoensis ) male gonad hydrolysates/ κ -carrageenan (SK) double cross-linking network hydrogels were constructed as curcumin (Cur) delivery vehicles with good gel mechanical property and homogeneous honeycomb microstructures. Compared with Cur + DSS group, weight loss and colon length in SK-Cur + DSS group increased about 1.04 and 1.06 folds, while the disease active index (DAI) scores decreased about 13 %. Moreover, SK-Cur showed superior effect on intestinal barrier improvement, oxidative stress modulation, and inflammatory expression regulation, reflected by 1.1 folds increment of epithelial tight junction proteins, 16 % and 27 % decline in MPO and iNOS levels, 20 % decline in NF-κB expression, 4 %, 7 %, 6 % decline in TNF-α, IL-1β, IL-6 expression in serum, and 9 %, 20 %, 7 % decline in TNF-α, IL-1β, IL-6 expression in colon tissue. Furthermore, SK-Cur enriched alpha diversity and restored taxonomic composition with increasing Bacteroides and Verrucomicrobia abundance accompanied by decreasing Firmicutes in DSS-induced UC mice, roughly to a normal gut flora state.
研究领域:
药学
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胃肠病学
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营养保健品
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生物医学工程
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
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IF 7.5
Xiongjie Sun,Yu Zhang,Gang Cheng,Tianxiang Zhu,Zhigang Zhang,Lei Xiong,Haiming Hu,Hongtao Liu
Ulcerative colitis (UC) has been confirmed as a disease with a high incidence and low cure rate worldwide. In severe cases, UC can develop into colon cancer. Modern research has confirmed that berberine (BBR) can treat UC by inhibiting the expressions of inflammatory factors. However, the contribution of gut microbiota and flora metabolites in treating UC with BBR remains unclear. In this study, the ameliorative effects of BBR on gut microbiota dysbiosis and flora metabolites were investigated in a dextran sodium sulfate (DSS)-induced UC rodent model. We found that BBR significantly improved the pathological phenotype, attenuated intestinal barrier disruption, and mitigated colonic inflammation in DSS mice. By 16 S rDNA sequencing, BBR alleviated gut microbiota dysbiosis in UC mice. Moreover, the gut microbiota depletion experiment confirmed that the therapeutic effect of BBR was inextricably correlated with the gut microbiota. Besides, the flora metabolites ( e.g. , short-chain fatty acids, bile acids, and 5-hydroxytryptamine) were studied using HPLC-MS. The results suggested that BBR ameliorated the bile acid imbalance induced by DSS in the liver and gut. Furthermore, BBR treatment repaired gut barrier damage. The above results revealed that BBR alleviated DSS-induced UC in mice by restoring the disturbed gut microbiota, elevating unconjugated and secondary bile acids in the gastrointestinal tract, and activating the FXR and TGR5 signal pathway. This study provides novel insights into the mechanism of BBR in treating UC.
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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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Min Zhou,Zhen-lin Liu,Jia-yu Liu,Xiao-bo Wang
Ulcerative colitis (UC) is a subtype of inflammatory bowel disease. Previous studies have suggested a link between senescence process and the body’s inflammatory reaction, indicating that senescence may exacerbate UC, yet the relation between UC and senescence remains unclear. Tedizolid Phosphate (TED), a novel oxazolidinone antimicrobial, is indicated in acute bacterial skin infections, its impact on senescence is not known. Our research revealed that the UC inducer dextran sulfate sodium (DSS) triggers senescence in both colon epithelial NCM460 cells and colon tissues, and TED that screened from a compound library demonstrated a strong anti-senescence effect on DSS treated NCM460 cells. As an anti-senescence medication identified in this research, TED efficiently alleviated UC and colonic senescence in mice caused by DSS. By proteomic analysis and experimental validation, we found that DSS significantly inhibits the AMPK signaling pathway, while TED counteracts senescence by restoring AMPK activity. This research verified that the development of UC is accompanied with colon tissue senescence, and TED, an anti-senescence medication, can effectively treat UC caused by DSS and alleviate colon senescence. Our work suggests anti-senescence strategy is an effective approach for UC treatment.
研究领域:
药理学
·
炎症性肠病
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细胞衰老
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信号转导
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Lin Niu,Shilong Wang,Yanyan Xu,Xingwang Zu,Xinyu You,Qiuyang Zhang,Pengwei Zhuang,Min Jiang,Jie Gao,Xiaotao Hou,Yanjun Zhang,Gang Bai,Jiagang Deng
Ethnopharmacological relevance As a classic traditional Chinese medicine , Magnolia officinalis ( M . officinalis ) is widely used in digestive diseases . It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. Aim of the study In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M . officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M . officinalis extract in treating IBD. Materials and methods To reveal the connection between the active ingredients in M . officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. Results Our finding elucidated that the inhibitory activity of M . officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. Conclusions The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Weilai Yu,Boyang Li,Luxi Chen,Qiu Chen,QingQing Song,Xiaosheng Jin,Yandan Yin,Haibin Tong,Liwei Xue
Ethnopharmacological relevance Dendrobium, recognized as “Shihu” in traditional Chinese medicine, holds a rich history of medicinal utilization documented in the Chinese Pharmacopoeia. Ancient texts like “Shen Nong Ben Cao Jing” extol Dendrobium 's virtues as a superior herbal medicine fortifying “Yin” and invigorating the five viscera. Dendrobium is extensively employed for the treatment of gastrointestinal inflammatory disorders, showcasing significant therapeutic efficacy, particularly against ulcerative colitis (UC), within the realm of Chinese ethnopharmacology. Dendrobium plays crucial pharmacological roles due to its rich content of polysaccharides, alkaloids, phenanthrenes, and bibenzyls. Gigantol, a prominent bibenzyl compound, stands out as one of the most vital active constituents within Dendrobium , the gigantol content of Dendrobium leaves can reach approximately 4.79 μg/g. Its significance lies in being recognized as a noteworthy anti-inflammatory compound derived from Dendrobium . Aim of the study Given the pivotal role of gigantol as a primary active substance in Dendrobium , the therapeutic potential of gigantol for gastrointestinal diseases remains enigmatic. Our present investigation aimed to evaluate the therapeutic effects of gigantol on dextran sulfate sodium (DSS)-induced colitis and reveal its potential mechanism in countering UC activity. Materials and methods The protective efficacy of gigantol against colitis was assessed by examining the histopathological changes and conducting biochemical analyses of colon from DSS-challenged mice. Assessments focused on gigantol's impact on improving the intestinal epithelial barrier and its anti-inflammatory effects in colonic tissues of colitis mice. Investigative techniques included the exploration of the macrophage inflammatory signaling pathway via q PCR and Western blot analyses. In vitro studies scrutinized macrophage adhesion, migration, and chemotaxis utilizing transwell and Zigmond chambers. Furthermore, F-actin and Rac1 activation assays detailed cellular cytoskeletal remodeling. The potential therapeutic target of gigantol was identified and validated through protein binding analysis, competitive enzyme-linked immunosorbent assay (ELISA), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. The binding sites between gigantol and its target were predicted via molecular docking. Results Gigantol ameliorated symptoms of DSS-induced colitis, rectified damage to the intestinal barrier, and suppressed the production of pro-inflammatory cytokines in colonic tissues. Intriguingly, gigantol significantly curtailed NF-κB signaling activation in the colons of DSS-induced colitis mice. Notably, gigantol impaired the β2 integrin-dependent adhesion and migratory capacity of RAW264.7 cells. Moreover, gigantol notably influenced the cytoskeleton remodeling of RAW264.7 cells by suppressing Vav1 phosphorylation and Rac1 activation. Mechanistically, gigantol interacted with β2 integrin, subsequently diminishing binding affinity with intercellular adhesion molecule-1 (ICAM-1). Conclusions In conclusion, these findings elucidate that gigantol ameliorates DSS-induced colitis by antagonizing β2 integrin-mediated macrophage adhesion, migration, and chemotaxis, thus it may impede macrophage recruitment and infiltration into colonic tissues. This study suggests that gigantol shows promise as a viable candidate for clinical colitis therapy.
研究领域:
药理学
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免疫学
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炎症性肠病
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传统中药
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分子生物学
✓ 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）