TOXICOLOGY
·
2025
·
IF 4.6
Liya Fang,Jinhua Xu,Chanlin Fang,Yuanxiang Jin
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a commonly used rubber protectant that continuously enters the environment via groundwater. Its oxidation product, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ), has garnered significant concern due to its reported toxicity in animals. This study aims to evaluate the intestinal toxicity and potential metabolic impact of 6PPD and 6PPDQ in mice following oral exposure to various doses. Our results demonstrate that both compounds compromise the intestinal barrier, as evidenced by significant increases in the expression of tight junction proteins (claudin-1 and occludin) and mucin protein (MUC2). These changes suggest an impairment of both the physical and chemical barriers of the intestine. Following exposure, there was a marked increase in pro-inflammatory cytokines (IL-6, IL-22, and NOD-1), indicating an inflammatory response associated with the disruption of lipid metabolism and macrophage polarization. Specifically, the shift from M2 to M1 macrophage polarization correlates with increased expression of M1 markers despite no change in the M1/M2 ratio over prolonged exposure. Furthermore, 6PPD exposure significantly reduced gut microbiota richness and evenness, with more pronounced changes observed in the 6PPDQ-treated group. Correlation analysis suggested that these microbial shifts may influence host carnitine and lipid metabolism pathways. Ultimately, both 6PPD and 6PPDQ exposure led to elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in the bloodstream, attributed to decreased TC esterification. These findings highlight the potential long-term health risks associated with environmental exposure to 6PPD and 6PPDQ, particularly concerning gut integrity and metabolic dysregulation. Synopsis This study investigates the toxicity of 6PPD and its transformation product 6PPDQ, revealing their detrimental effects on intestinal health, disruption of gut microbiota, and alterations in lipid metabolism, highlighting significant implications for both environmental and human health.
研究领域:
毒理学
·
环境健康
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分子生物学
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代谢学
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微生物组学
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免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Peptide Research and Therapeutics
·
2018
·Vol. 25
·期 2
·573-582
·
IF 1.132
Liu Huifan,Ma Juanjuan,Yin Zhina,Wu Hui
To characterize the digestive properties of an antioxidative peptide fraction (DA-P peptide) extracted from Dendrobium aphyllum and its effects following fermentation, DA-P peptide was used as a substrate for artificially stimulated in vitro gastrointestinal digestion and fermentation by human fecal microbiota. After in vitro digestion, the reducing power and DPPH- and ABTS- free radical-scavenging capabilities of DA-P peptide were significantly improved. During fermentation, changes in pH, peptide contents, and enzyme activities were evaluated and the results were well-correlated with each other; DA-P peptide lowered the pH value of the fermentation environment and stimulated the proliferation and metabolism of intestinal flora, indicating that DA-P peptide enhanced colon health. Thus, DA-P peptide showed antioxidative activities after gastrointestinal digestion and beneficial effects on intestinal flora when fermented by gut microbiota. Our results provide a foundation for studies of D. aphyllum peptide, which has not been widely examined.
研究领域:
食品科学
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微生物学
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植物化学
✓ 已验证
产品关联
DOI
高影响因子
Clinical and Translational Medicine
·
2023
·Vol. 13
·期 4
·e1227
·
IF 10.6
Peijie Zhong,Hang Wu,Yuanqiao Ma,Xiaoxiao Xu,Yizhuo Jiang,Chaolei Jin,Qiaozhen Zhu,Xinlei Liu,Zhimin Suo,Junpeng Wang
Background Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild-type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS-induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor-positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild-type C57BL/6 mice. Further antibiotic-treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4 . Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.
研究领域:
免疫学
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胃肠病学
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微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Anqi Xie,Haihua Ji,Zheyi Liu,Yiqun Wan,Xuecong Zhang,Huihuang Xiong,Shao-Ping Nie,Hao Wan
Oral administration of probiotics is a promising method to alleviate inflammatory bowel diseases (IBDs). However, gastrointestinal environmental sensitivity and inferior intestinal colonization of probiotics hinder the alleviation effect. Here, we developed a simple yet effective modified prebiotic-based “shield” (Fe-TA@mGN) composed of an Fe3+-tannic acid cross-linking network and carboxymethylated β-glucan for arming Escherichia coli Nissle 1917 (EcN@Fe-TA@mGN). The Fe-TA@mGN “shield” not only acted as a dynamic barrier to enhance the gastrointestinal stress resistance ability of EcN but also aided the intestinal colonization of EcN as well as synergized with EcN for the alleviation of dextran sulfate sodium (DSS) induced colitis. More specifically, with the protection of the Fe-TA@mGN “shield”, the survival rate of armed EcN could be up to ∼1720 times higher than that of bare EcN after exposure to simulated gastric fluid. Excitingly, the intestinal retention rate of EcN@Fe-TA@mGN was as high as 47.54 ± 6.06% at 16 h post-administration, while almost all bare EcNs were excreted out at 8 h post-administration. With all of the aforementioned attributes, EcN@Fe-TA@mGN efficiently alleviated colitis, verified by the repair of the intestinal barrier and the attenuation of inflammation. Moreover, for EcN@Fe-TA@mGN, mGN synergized with EcN to positively modulate gut microbiota and promote the production of short-chain fatty acids (SCFAs, especially for butyric acid, a primary source for maintaining intestinal health), both of which would further advance the alleviation of colitis. We envision that the strategy developed here will inspire the exploitation of various prebiotics to arm probiotics for the effective alleviation of IBD.
研究领域:
微生物学
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药学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Lu Xu,Qin Zhao,Yiqiong Xie,Ge Bai,Hongwen Liu,Qi Chen,Hongjue Duan,Lishan Wang,Hang Xu,Yuxiang Sun,Gao Ling,Weihong Ge,Yun Zhu
Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.
研究领域:
药理学
·
胃肠病学
·
生物医学工程
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Jingyi Hu,Hai Huang,Yuan Che,Chujie Ding,Lu Zhang,Yun Wang,Haiping Hao,Hong Shen,Lijuan Cao
Ethnopharmacological relevance Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract, consisting of ulcerative colitis (UC) and Crohn's disease (CD). Gut microbiota and their metabolites may play a role in the pathogen of IBD, especially of the UC. Qingchang Huashi Formula (QHF), a traditional Chinese medicine formula, has shown therapeutic effect on treating UC based on the clinical practice without clear pharmacological mechanism. Aim of the study The aim of this study was to clearly define the effect of QHF and its components, Baitouweng (PBR) and Baizhi (ADR) on treating UC. Materials and Methods Pharmacodynamic effects of QHF and single herb were evaluated in dextran sulfate sodium (DSS) induced acute or chronic colitis mice. Body weight loss, disease activity index (DAI) and colon length were estimated. Histological changes were observed by H&E staining. The number and abundance of gut microbiota were measured with 16S rRNA sequencing. LC-MS and GC-MS were used to detect the concentration of metabolites (e.g., bile acids (BAs) and short chain fatty acids (SCFAs)). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining and the crypt stem cell was estimated by immunohistochemical analyses. The colorectal tissues were used to detect levels of IL-1β, IL-6 and TNF-α by ELISA or qRT-PCR. The expression of NLRP3, Caspase 1 and IL-1β were examined by western blotting . Results QHF significantly inhibited colitis, protected mice from the loss of body weight and colon shorten. Comparatively, ADR and PBR showed strong efficacy in inhibiting DSS-induced colitis. We verified that while ADR was responsible for QHF's effect on maintaining gut microbiota homeostasis and metabolism, PBR was more prominent in keeping crypt stem cells proliferation and colonic goblet cells function. Moreover, we demonstrated that the alleviation of colitis by QHF was associated with the restoration of gut microbiota-metabolism homeostasis, protection of intestinal epithelial barrier and regulation of NLRP3/IL-1β pathway. Conclusions The finding of the present study suggested that QHF is curative in DSS-induced colitis by restoring gut microbiota-metabolism homeostasis and goblet cells function. An optimized QHF was constituted by ADR and PBR, which showed comparable efficacy on colitis to that of QHF. Our work probed out the active constitutes as well as the relevant pharmacological mechanisms of QHF, shedding light on potential new drug combination for the treatment of IBD.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Qianru Gao,Weiyi Tian,Huabing Yang,Haiming Hu,Junping Zheng,Xiaowei Yao,Baifei Hu,Hongtao Liu
Ethnopharmacological relevance Shen-Ling-Bai-Zhu-San (SLBZS) is a classic formula for strengthening the spleen and dispelling dampness, which has shown excellent efficacy in inflammatory bowel disease (IBD) in traditional Chinese medicine clinical studies. However, its exact pharmacological mechanism needs to be further elucidated. Aim of the study This study aims to investigate the restorative effect and mechanism of SLBZS on disturbed intestinal homeostasis in DSS-induced colitis mice. Materials and methods A colitis model was induced by 3% dextran sulfate sodium (DSS) for seven days, and SLBZS was administered by gavage. The influence of SLBZS on DSS-induced clinical symptoms and disease activity index (DAI) was monitored and analyzed. Alcian blue and fluorescein isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA) staining were used to assess intestinal mucus changes. The expression of intestinal barrier function indexes and immune-associated indexes were determined by H&E staining, real-time quantitative PCR (RT-qPCR), and Western blot. And gut microbiota changes were detected by 16 S rDNA sequencing technology. The antibiotic experiment was used to explore the role of gut microbiota in SLBZS treatment. Results The results showed that SLBZS significantly improved the physiological indexes including body weight, DAI score, and colon length of colitis mice. We focused on the effects of SLBZS on intestinal homeostasis in colitis mice. First, SLBZS could enhance the secretion of intestinal mucin and the expression levels of tight junctions and adhesive junctions. Second, SLBZS inhibited the expression level of inflammatory factors and reduced the protein expression level of NLRP3 inflammasome. Third, 16 S rDNA sequencing analysis revealed that SLBZS repaired the dysfunctional gut microbiota of colitis mice, such as enhancing the abundance of short-chain fatty acid-producing bacteria including Faecalibaculum , Colidextribacter , and Coprococcus . Further, by gut microbiota-depleted mice, we found that SLBZS could not exert an anti-colitis effect when gut microbiota was absent. Conclusions SLBZS restored intestinal environmental homeostasis by enhancing intestinal barrier function, inhibiting NLRP3 inflammasome, and restoring disturbed gut microbiota. And SLBZS could not ameliorate colitis mice with depleted gut microbiota. Our finding provided a theoretical basis for the clinical application of SLBZS in IBD.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
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
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Nutrition
·
2025
·
IF 5.1
Min Du,Xinran Liu,Xu Ji,Yue Wang,Xiaodan Liu,Chunfang Zhao,Erhui Jin,Youfang Gu,Hongyu Wang,Feng Zhang
Introduction: Enterotoxic Escherichia coli (ETEC) is the main pathogen that causes diarrhea, especially in young children. This disease can lead to substantial morbidity and mortality and is a major global health concern. Managing ETEC infections is challenging owing to the increasing prevalence of antibiotic resistance. Berberine, categorized as a substance with similarities in “medicine and food,” has been used in China for hundreds of years to treat gastrointestinal disorders and bacteria-induced diarrhea. This study investigated the preventive effect of dietary berberine on the intestinal mucosal barrier induced by ETEC and the microbial community within the intestines of weaned piglets.Methods: Twenty-four piglets were randomly divided into four groups. Piglets were administered either a standard diet or a standard diet supplemented with berberine at concentrations of 0.05 and 0.1%. and orally administered ETEC or saline.Results: Dietary supplementation with berberine reduced diamine oxidase, d-lactate, and endotoxin levels in piglets infected with ETEC (P < 0.05). Berberine increased jejunal villus height, villus/crypt ratio, mucosal thickness (P < 0.05), and goblet cell numbers in the villi and crypts (P < 0.05). Furthermore, berberine increased the optical density of mucin 2 and the mucin 2, P-glycoprotein, and CYP3A4 mRNA expression levels (P < 0.05). Berberine increased the expressions of zonula occludins-1 (ZO-1), zonula occludins-2 (ZO-2), Claudin-1, Occludin, and E-cadherin in the ileum (P < 0.05). Moreover, berberine increased the expression of BCL2, reduced intestinal epithelial cell apoptosis (P < 0.05) and decreased the expression of BAX and BAK in the duodenum and jejunum, as well as that of CASP3 and CASP9 in the duodenum and ileum (P < 0.05). Berberine decreased the expression of IL-1β, IL-6, IL-8, TNF-α, and IFN-γ (P < 0.05) and elevated total volatile fatty acids, acetic acid, propionic acid, valeric acid, and isovaleric acid concentrations (P < 0.05). Notably, berberine enhanced the abundance of beneficial bacteria including Enterococcus, Holdemanella, Weissella, Pediococcus, Muribaculum, Colidextribacter, Agathobacter, Roseburia, Clostridium, Fusicatenibacter, and Bifidobacterium. Simultaneously, the relative abundance of harmful and pathogenic bacteria, such as Prevotella, Paraprevotella, Corynebacterium, Catenisphaera, Streptococcus, Enterobacter, and Collinsella, decreased (P < 0.05).Discussion: Berberine alleviated ETEC-induced intestinal mucosal barrier damage in weaned piglets models. This is associated with enhancement of the physical, chemical, and immune barrier functions of piglets by enhancing intestinal microbiota homeostasis.
研究领域:
医学
·
微生物学
·
兽医学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 6
·2466
·
IF 4.9
Yuwei Ye,Abudumijiti Abulizi,Yukun Zhang,Feng Lu,Yongpan An,Chaoqun Ren,Hang Zhang,Yiming Wang,Dongmei Lin,Dan Lu,Min Li,Baoxue Yang
Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.
研究领域:
医学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
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
·
微生物学
·
营养学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2019
·Vol. 9
·期 9
·486
·
IF 4.694
Xuan Li,Mingyu Mao,Yanan Zhang,Kaifan Yu,Weiyun Zhu
Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle in all aerobic organisms, and is also a vital microbial metabolite in the gut. Although succinate is known to regulate intestinal metabolism and immune function, its role in the protection of the intestinal epithelial barrier function and inflammation is poorly characterized. In this study, we evaluated the effects of succinate on intestinal epithelial barrier function and inflammation in pigs. Twenty-four growing pigs were distributed into three groups (n= 8) and received either a basal diet (control group) or the same diet supplemented with 0.1% succinate or 1% succinate. The diet supplemented with 1% succinate led to alterations in the intestinal morphology. We confirmed in vitro that 5 mM succinate treatment modulated intestinal epithelial permeability by increased transepithelial electrical resistance (TEER) in intestinal porcine epithelial cell (IPEC)-J2 cells. Furthermore, succinate treatment increased the abundance of tight junction proteins claudin-1, zona occluden (ZO)-1, and ZO-2 in the jejunum in vivo and in vitro. In addition, dietary succinate supplementation promoted the expression of inflammatory cytokines interleukin (IL)-25, IL-10, IL-8, and IL-18 in the jejunum. Taken together, these data identify a novel role of succinate in the modulation of intestinal epithelial barrier function, which may be a nutritional target to improve gut health in animals.Keywords:succinate;intestinal epithelial barrier;intestinal inflammation;pigs
研究领域:
营养学
·
免疫学
·
动物科学
✓ 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）