PHYTOMEDICINE
·
2025
·
IF 8.3
Linlin Ding,Qingjie Li,Kaige Qi,Yonghui Chen,Na Hu,Sangyu Hu,Tianqi Fang,Shuang Guan,Jianfeng Wang,Jiazhang Qiu,Xuming Deng,Lei Xu
Background Salmonella pullorum ( S. pullorum ) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate intestinal microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated. Purpose This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks. Methods H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum -infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection. Results Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum -infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium , and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum -induced intestinal barrier damaged and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis. Conclusion These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum -infected chicks.
研究领域:
微生物学
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免疫学
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分子生物学
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兽医学
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代谢组学
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药理学
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DOI
PubMed
高影响因子
PLoS Neglected Tropical Diseases
·
2024
·Vol. 18
·期 12
·e0012714
·
IF 3.4
Xuanyin Cui,Yi Cheng,Hongyan Wang,Xiaomao Li,Jinfu Li,Ke Zhang,Rong Mou
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an unknown etiology and is difficult to treat. Studies have shown that some helminths and their associated products have therapeutic potential in controlling or preventing inflammatory diseases. This study is to investigate the mitigation effects of Hymenolepis nana antigens (HnAg) on the UC model. HnAg significantly improved the disease activity index, colon length, and colonic pathological damage in mice with dextran sulfate sodium (DSS)-induced colitis. HnAg intervention could protect the number of goblet cells and enhance the expression of tight junction proteins and mucins, thereby improving intestinal barrier integrity. HnAg attenuated small intestinal organoid damage and stimulated intestinal stem cells proliferation in a DSS-induced mouse organoid inflammation model. The protective mechanism of HnAg might be related to the activation of the aryl hydrocarbon receptor (AhR)/IL-22 signaling pathway, which regulates intestinal barrier function and promotes the proliferation and differentiation of intestinal stem cells. In conclusion, HnAg has a therapeutic effect on UC mice. Our study provides a new approach for alleviating UC by Hymenolepis nana and its associated products.
Ulcerative colitis (UC) is an immune-mediated chronic inflammatory disease. Currently, commonly used drugs such as aminosalicylates and glucocorticosteroids are difficult to treat and have many adverse effects. In recent years, there has been a growing interest in utilizing the immunomodulatory abilities of worms to develop new therapies for the treatment of inflammatory and allergic diseases. Hymenolepis nana is a zoonotic parasitic worm that parasitizes the small intestines of humans and rodents and generally does not cause serious pathologic damage to their hosts, making it a potential class of intestinal parasites in helminthic therapy. In this study, we investigated the mitigating effect of Hymenolepis nana antigens (HnAg) on UC in mice from the perspective of maintaining intestinal mucosal barrier integrity. The results showed that HnAg alleviated UC in mice by activating the aryl hydrocarbon receptor (AhR)/IL-22 signaling pathway, promoting the proliferation and differentiation of intestinal stem cells, and modulating the integrity of the intestinal mucosal barrier. Meanwhile, HnAg attenuated DSS-induced inflammatory damage in mouse small intestinal organoid tissues and promoted intestinal stem cells proliferation. Suggesting that Hymenolepis nana and its related products may become a new option for alleviating UC.
研究领域:
免疫学
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胃肠病学
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药理学
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炎症性肠病
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DOI
PubMed
高影响因子
Food & Function
·
2023
·
IF 6.1
Jiachen Zhuang,Qianqian Wang,Fei Shen,Jing Wang,Juan Du,Peng Yu,Fengqin Feng,Minjie Zhao
This study investigated the immunomodulatory effects of soft-shelled turtle (Pelodiscus sinensis) peptide (TP) and Chinese pond turtle (Chinemys reevesii) peptide (TMP) on the intestinal mucosal immune system (IMIS). The results demonstrated that TP and TMP improved holistic immunity by restoring the vital immune organ atrophy and proliferation capacity of spleen immune cells. Moreover, TP and TMP significantly increased the serum content of IgA and cytokines that are responsible for immune cell activation and antigen clearance. TP and TMP promoted intestinal B cell activation, class switching recombination, and antibody secreting processes in a T cell-independent manner to increase the SIgA content. Furthermore, TP and TMP enhanced the intestinal barrier by increasing the protein expression of tight junctions (TJs) and adhesion junctions (AJs) and ameliorating the intestinal morphology. Mechanistically, TP and TMP activated the AHR/IL-22/STAT3/IL-6 axis to enhance the IgA response and improve the intestinal barrier, indicating their potential in intestinal health modulation.
研究领域:
免疫学
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胃肠病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Jianhong Luo,Yuhao Jiang,Xudong Yin,Wenliang Xue,Jinyu Liu,Muyaxin Wang,Shasha Shi,Yuepu Pu,Xinsong Li
Acute liver injury (ALI), characterized by rapid hepatocyte damage induced by drugs, toxins, or viral infections, lacks clinically effective targeted therapies. Usually, the impaired hepatocytes significantly inhibit the uptake of medicines, leading to poor bioavailability and therapeutic outcome. Herein, a combination of hepatocyte growth factor (HGF) and interleukin-22 (IL-22) mRNAs delivered by N-acetylgalactosamine modified lipid nanoparticles (GalNAc-LNP) was developed to treat ALI. Tetra-antennary GalNAc cholesterol conjugate was first synthesized and incorporated into conventional LNP to encapsulate HGF/IL-22 mRNAs. After that, ALI mice model was applied to test the delivery effect of GalNAc-LNP. It was found that the GalNAc-LNP overcame delivery barriers caused by necrosis and inflammation, increasing protein expression of the encapsulated mRNA in the liver by 121.0%, owing to GalNAc- ASGPR targeting. Importantly, HGF/IL-22 mRNAs combination encapsulated within GalNAc-LNP markedly reduced necrotic foci, promoted hepatocyte regeneration, alleviated inflammatory response and accelerated recovery of liver function. The results demonstrated the synergistic effects of HGF-driven hepatocyte proliferation and IL-22-mediated inhibition of hepatic inflammation. Taken together, HGF/IL-22 mRNAs delivered by GalNAc-LNP possesses dual-target synergistic therapeutic output, holding potential for the treatment of ALI.
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DOI
PubMed
高影响因子
Engineering
·
2025
·
IF 11.6
Huanyu Li,Ziwei Yang,Chuanyu Zhang,Xueyong Wei,Wenjing Wang,Ting Bai,Zhichao Deng,Bowen Gao,Manli Cui,Weixuan Jing,Mingzhen Zhang,Zhaoxiang Yu,Mingxin Zhang
Ulcerative colitis (UC) is a chronic, non-specific inflammatory disorder of the intestines whose etiology is influenced by various factors. Intestinal barrier impairment due to disturbances in the intestinal microenvironment is a key feature of UC. Current therapeutic strategies are constrained in their capacity to fully restore the intestinal barrier and achieve comprehensive resolution of inflammation in a coordinated manner. In this study, we constructed a pterostilbene (PSB)-loaded prebiotic microcapsule (PSB@MC) using a microfluidic electrospray method and characterized it using various means. Its safety, biodistribution, protective, and therapeutic effects on colitis were evaluated in various animal models. The potential mechanisms by which PSB@MC exerts its therapeutic effects were subsequently explored. The results indicated that PSB@MC exhibited favorable biocompatibility and facilitated targeted delivery of PSB to the colon. Moreover, the wrinkled morphology of PSB@MC contributed to prolonged drug retention in the colon. Oral PSB@MC administration restored intestinal microenvironment homeostasis by scavenging reactive oxygen species (ROS), decreasing pro-inflammatory cytokines, modulating gut microbiota and metabolism, and providing protective and therapeutic benefits against dextran sulfate sodium-induced colitis. Additionally, our research demonstrated that PSB@MC could activate the aryl hydrocarbon receptor/interleukin-22 (AHR/IL-22) pathway to enhance the integrity of the intestinal barrier. These results suggest that PSB@MC could be a new, secure, and efficient UC therapy option.
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Yu Zhang,Zhihong Zhou,Zeming Zhang,Yan Liu,Wenting Ji,Jinglin Wang,Kaiping Wang,Qiang Li
Ulcerative colitis (UC) involves chronic, complex pathology of the intestinal mucosa. Current treatments are limited in efficacy and associated with adverse effects, highlighting the urgent need for improved therapeutic options. Lentinan (LNT), a polysaccharide drug commonly used in clinical immune modulation therapies, shows potential for UC treatment, though its specific targets and mechanisms remain unclear. In this study, LNT administration effectively mitigated DSS-induced colitis in mice, enhanced mucosal barrier function and antimicrobial defense. Specifically, LNT modulated the balance between tissue-resident and infiltrating macrophages, thereby improving pathogen clearance and enhancing the immunological barrier. Notably, we identified a novel effect of LNT in regulating the macrophage Dectin-1-ILC3 axis to increase IL-22 secretion. This led to the modulation of epithelial O-glycan fucosylation, antimicrobial peptides, and epithelial stem cells, thereby strengthening antimicrobial defenses and the physicochemical barrier. Neutralization with anti-IL-22 antibodies diminished the therapeutic effect of LNT in UC, underscoring the critical role of IL-22 in LNT-mediated treatment. Overall, this study highlights the potential of LNT as a novel therapeutic agent for UC, offering new insights into its molecular mechanisms and clinical application.
研究领域:
免疫学
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胃肠病学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Jiali Wang,Xianhai He,Zhirong Jia,Aiwen Yan,Kang Xiao,Shuo Liu,Mengjun Hou,Yaling Long,Xuansheng Ding
Context Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Gefitinib is a first-line treatment for NSCLC. However, its effectiveness is hindered by the development of drug resistance. At present, Shenqi Fuzheng injection (SFI) is widely accepted as an adjuvant therapy in NSCLC.Objective This study investigates the molecular mechanism of SFI when combined with gefitinib in regulating cell progression among EGFR-TKI-resistant NSCLC.Materials and methods We established gefitinib-resistant PC9-GR cells by exposing gefitinib escalation from 10 nM with the indicated concentrations of SFI in PC9 cells (1, 4, and 8 mg/mL). Quantitative real-time polymerase chain reaction was performed to assess gene expression. PC9/GR and H1975 cells were treated with 50 ng/mL of interleukin (IL)-22 alone or in combination with 10 mg/mL of SFI. STAT3, p-STAT3, AKT, and p-AKT expression were evaluated using Western blot. The effects on cell proliferation, clonogenicity, and apoptosis in NSCLC cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and flow cytometry assays.Results SFI treatment alleviated the development of gefitinib resistance in NSCLC. PC9/GR and H1975 cells treated with SFI significantly exhibited a reduction in IL-22 protein and mRNA overexpression levels. SFI effectively counteracted the activation of the STAT3/AKT signaling pathway induced by adding exogenous IL-22 to PC9/GR and H1975 cells. Moreover, IL-22 combined with gefitinib markedly increased cell viability while reducing apoptosis. In contrast, combining SFI with gefitinib and the concurrent treatment of SFI with gefitinib and IL-22 demonstrated the opposite effect.Discussion and Conclusion SFI can be a valuable therapeutic option to address gefitinib resistance in NSCLC by suppressing the IL-22/STAT3/AKT pathway.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Junzhi,Lin Binyan,Zhang Ying,Hu Xiaochao,Liu Tongtong,Liu E-Hu,Liu Shijia
Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored.Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice.Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels.Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway.Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
研究领域:
药理学
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胃肠病学
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免疫学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Yuli Ge,Huiling Sun,Lanman Xu,Weiping Zhang,Jiaojian Lv,Yongping Chen
Alcoholic liver disease (ALD) is a common clinical liver injury disease. Lactobacillus rhamnosus Gorbach-Goldin (LGG) has been revealed to alleviate alcohol-induced intestinal barrier and liver injury. However, the underlying mechanism of LGG treatment for ALD remains unclear. To clarify this aspect, a chronic plus binge ALD model was constructed using C57BL/6 mice in line with a chronic alcohol binge feeding protocol. Interleukin 22 (IL-22) level was determined by quantitative real-time polymerase-chain reaction and enzyme-linked immunosorbent assays. Effects of LGG in model or IL-22 knockdown in LGG-treated model on the liver injury and steatosis status, as well as intestinal barrier function were assessed by hematoxylin eosin (HE) staining. Levels of alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) in serum were measured by the corresponding kit. Western blot analysis was conducted to detect protein expressions of intestinal tight junction protein 1 (ZO-1) and Claudin-1. Concretely, LGG elevated IL-22 level in liver tissues and serum, while inhibiting ALT, TG, and AST levels in alcohol-exposed mice. Moreover, LGG alleviated liver injury, steatosis, and intestinal barrier injury caused by alcohol, and enhanced ZO-1 and Claudin-1 expressions. Furthermore, IL-22 knockdown increased ALT, TG, and AST levels in serum, and aggravated liver injury, steatosis, and intestinal barrier injury. ZO-1 and Claudin-1 levels were downregulated by IL-22 silencing. Importantly, downregulation of IL-22 reversed the effect of LGG on the liver and intestinal barrier injury. To conclude, LGG protects against chronic alcohol-induced intestinal and liver injury via regulating the intestinal IL-22 signaling pathway.
研究领域:
胃肠病学
·
免疫学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Hydrocolloids for Health
·
2025
·
IF 5.1
Yingzhu He,Ze Ma,Hejing Shen,Bei Fan,Xiang Li,Qin Tian,Fengzhong Wang,Yajuan Bai
The bioactivity of Alpinia oxyphylla fruit polysaccharides (AFP) is closely linked to their extraction-determined structural properties. This study systematically compared three extraction methods (ultrasound-assisted enzymatic (AFP-UE), pure ultrasound (AFP-U), and hot water (AFP-H)) for their efficiency in extracting AFP and influencing their structural features and intestinal barrier protective effects. Although AFP-UE yielded the highest extraction efficiency (4.75%) and exhibited predominantly a neutral arabinogalactan, it was AFP-U (comprises mixed rhamnogalacturonan-I and homogalacturonan domains alongside notable glucan motifs) that demonstrated the most potent intestinal barrier protection in a dextran sulfate sodium (DSS)-induced zebrafish colitis model. At 50 μg/mL, AFP-U significantly reduced the pro-inflammatory cytokine TNF-α, while upregulating anti-inflammatory cytokine IL-4, tight junction protein ZO-1, and mucin 2. Mechanistically, AFP-U is very likely to mainly alleviated oxidative stress and promoted intestinal barrier repair primarily by activating the IL-22 pathway, as evidenced by enhanced IL-22/IL-10 expression and suppression of IL-22 Receptor Subunit Alpha-2 (IL-22RA2). These findings highlight the critical role of extraction methods in shaping polysaccharide structure and bioactivity, positioning pure ultrasound extraction as a green and efficient strategy for producing functional polysaccharides with enhanced gastrointestinal health benefits.
研究领域:
天然产物化学
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食品科学
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免疫学
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分子生物学
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胃肠病学
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中药学
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li
The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.
研究领域:
放射生物学
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药理学
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分子生物学
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免疫学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Yu Ma,Ming Liu,Donghui Li,Jie Li,Zixin Guo,Yunjun Liu,Shengnan Wan,Yixiang Liu
The numerous health benefits of olive oil are widely known, however, it also provides anti-allergic properties that have not yet been fully defined. In this study, the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested 600 mg/(kg∙day) olive oil for two weeks prior to the evaluation. An allergy model was subsequently constructed for analysis, the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice, and up-regulated the hypothermia and the decline in the immune organ index. Moreover, fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group. In addition, analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1) and IL-22, and helped maintain the integrity of the intestinal epithelial physical barrier. Increased levels of mucin 2 and β -defensin were also found in the intestinal mucus of the olive oil-treated mice. These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice, and had a positive effect on intestinal epithelial mucosal immunity.
研究领域:
免疫学
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胃肠病学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）