JOURNAL OF INORGANIC BIOCHEMISTRY
·
2021
·
IF 4.155
Kun Chen,Yuan Liu,Mu Li,Lu Liu,Qiang Yu,Long Wu
Here we show that Preyssler-type polyoxotungstates (Preyssler-type POTs, [NaP 5 W 30 O 110 ] −14 ) complexed with peptides can prevent the dysbiotic expansion of anaerobic bacteria of the Enterobacteriaceae family. In a dextran sulfate sodium (DSS)-induced colitis model, symptom remission of C57BL/6 J mice with colitis is achieved by orally treated with POT complexes. Ten days of daily administration of POT complexes reduces 5% body weight loss and the mRNA levels of proinflammatory markers (77% reduction for Il6 , 73% reduction for Tnf , 91% reduction for Cxcl1 ) in the caecum and proximal colon. Bacterial population analysis reveals that these Enterobacteriaceae population in the caecal content decline by one order of magnitude after administration of POT complexes. POT complexes exert anti-inflammatory effects indirectly on the host immune system by inhibition of malignant expansion of anaerobic Enterobacteriaceae during gut inflammation. Furthermore, POTs show negligible effect on bacterial growth in vitro, healthy mice and their microbiota composition under homeostatic conditions. Rationally designed POT complexes will provide distinctive approach to improve enteric bacteria dysbiosis-associated gut inflammation by balancing bacterial communities.
研究领域:
微生物学
·
免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xiangli He,Jiayan Cui,Hui Ma,Naijipu Abuduaini,Ying Huang,Lu Tang,Wanyan Wang,Yuanyuan Zhang,Yang Wang,Weiqiang Lu,Bo Feng,Jin Huang
Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting reaction in the de novo synthesis pathway of guanine nucleotides that is highly required for cancer cell outgrowth. Herein, we found that IMPDH isoform 2 (IMPDH2) is highly expressed in colorectal cancer (CRC) and is correlated with poor patient prognosis. Via structure-based virtual screening, we identified berberrubine, a critical ingredient of the medical plant Coptis chinensis, as a novel, selective, and competitive inhibitor of IMPDH2, which demonstrated over 15-fold selectivity to IMPDH2 than IMPDH1. Besides, we also confirmed the interaction between berberrubine and IMPDH2. Of note, berberrubine treatment significantly impairs the growth of human CRC cells in a dose-dependent manner, which can be rescued by supplementing with guanosine. Furthermore, oral administration of berberrubine remarkably reduced tumor volume and weight in a human cell line-derived xenograft model. Importantly, the anti-cancer activity of berberrubine was also confirmed by using the azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced spontaneous CRC mouse model. Taken together, our study highlights that berberrubine acts as a novel IMPDH2 inhibitor, suppressing the growth of CRC in vitro and in vivo , providing a fresh perspective for its potential application in the treatment of CRC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Haiou Wang,Wenkang Huang,Xiaoya Pan,Meizi Tian,Jiahui Chen,Xiaotong Liu,Qin Li,Jianhua Qi,Yiping Ye,Lijuan Gao
Purpose To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).Methods The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).Results Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1β, and TNF-α levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like Lachnospiraceae_NK4A136_group and Alloprevotella and concurrently reduced the pathogenic bacteria such as Escherichia-Shigella, [Eubacterium]_siraeum_group, and Parabacteroides. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.Conclusion QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.
研究领域:
药理学
·
分子生物学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Yue Meng,Fangfang Su,Yuhan Cui,Hanying Yang,Qian Guo,Wei Zhang,Ling Guo,Yujun Jiang,Chaoxin Man,Yu Zhang
Probiotics have shown potential in alleviating ulcerative colitis (UC) by modulating gut microbiota, restoring intestinal barrier integrity, and suppressing inflammatory responses. However, their oral efficacy is limited by poor gastrointestinal survival and insufficient colonic targeting. To address these limitations, a ternary hydrogel microcapsule (JYPWH) composed of apple pectin, whey protein isolate, and hyaluronic acid (HA) was developed to encapsulate Lacticaseibacillus rhamnosus JY027. As a dual-functional delivery system, JYPWH combined probiotic protection against gastrointestinal stress with HA-CD44-mediated delivery to inflamed colonic tissue. Oral administration of JYPWH significantly alleviated DSS-induced colitis in mice. Mechanistically, JYPWH promoted intestinal barrier repair by upregulating MUC-2, ZO-1, and Occludin. Concurrently, the NF-κB signaling pathway was suppressed in colonic tissue, serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were decreased, and serum levels of the anti-inflammatory cytokine IL-10 were increased. JYPWH also reduced inflammation-induced CD44 overexpression in colonic tissue. In addition, JYPWH reshaped the gut microbiota of DSS-treated mice by increasing beneficial taxa such as Lachnospiraceae_NK4A136_group and decreasing opportunistic pathogens, including Escherichia-Shigella , while restoring colonic short-chain fatty acid levels. Collectively, JYPWH integrates probiotic protection with HA-CD44-mediated colonic delivery, offering a promising strategy for UC intervention.
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2025
·
IF 5.4
Yina Huang,Yao He,Yunjie Cai,Yubin Cheng,Xunmei Shi,Jingyu He,Kesheng Wu,Hua Wei
Black tea is commonly used for tea beverage production and has been shown to be an effective natural ingredient to prevent experimentally induced colitis. However, there is limited evidence to show whether black teas of different origins demonstrate similar anti-inflammatory capacity in colitic mice. In this study, mice were daily administered with black tea extracts of lapsang, keemun or dianhong for 1 week prior to receiving 4% dextran sulfate sodium for inducing colitis. Both the lapsang and keemun extracts exhibited better anti-inflammatory effects than dianhong extract, as evidenced by the former two tea extracts that enhanced intestinal barrier functions (up-regulation of MUC2 and ZO-1 and increased population of goblet cells), and decreased colonic and serum pro-inflammatory cytokines. We deduced that GC might be a key contributor to the anti-colitis effects of black tea, potentially through synergistic interactions with other components at an optimal ratio to enhance anti-inflammatory efficacy. Fecal microbiome analysis showed that gut microbiome was differentially modulated by lapsang and keemun extracts. Their anti-colitic effects were dependent on gut microbiome as shown by the loss of such protection in DSS mice treated with broad-spectrum antibiotics (ABX) for significant microbiome alterations. Mechanistically, colonic transcriptomic analysis showed the differential impact of lapsang and keemun extracts on colitis via modulating gene expressions of IL-17 pathway and glutamatergic synapse, respectively. Further qPCR and immunohistochemistry assays verified aforementioned pathway modulation. Together, our study provided a roadmap for understanding the effects of different black tea types on colitis and for providing potential directions on nutritional modulation of colitis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2025
·
IF 9.7
Hongke Wei,Xiaomin Wang,Jiaqi Wang,Shijie Ren,Luis A.J. Mur,Dong Lu,Duo Cao
To valorize sour jujube ( Ziziphus acidojujuba ) leaves, this work focused on the extraction, quantification, and bioactivity assessment of flavonoids. First, ultrasound-assisted extraction (UAE) was employed to extract total flavonoids from sour jujube leaves (SJL-TF), with the procedure optimized through single-factor design and response surface methodology (RSM). SJL-TF yield reached 48.47 ± 0.36 mg/g under optimal circumstances, which included 61 % ethanol as extraction medium, an ultrasound power of 300 W, an extraction time of 33 min, and a liquid–solid ratio of 16 mL/g, showing higher extraction efficiency in comparison to the traditional Soxhlet extraction method. Scanning electron microscopy (SEM) analysis indicated that ultrasound treatment severely damaged the structural integrity of sour jujube leaves, which was more conducive to improving the SJL-TF yield. Then, polyamide resin chromatography was used to purify the crude SJL-TF extracts, increasing the SJL-TF purity by 3.2-fold to 74.58 ± 0.63 %. By developing and validating a UPLC-QQQ-MS/MS method, ten main flavonoids in SJL-TF extracts, including catechin, rutin, isoquercetin, narirutin, nicotiflorin, quercitrin, phlorizin, luteolin, quercetin, and apigenin, were successfully detected concurrently for quality control purposes. Furthermore, the purified SJL-TF showed a strong ameliorative effect on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice, as evidenced by significant mitigation of colonic inflammation and pathological damage. Thus, this work will contribute to improving the application of sour jujube leaves, especially in the pharmaceutical sector.
研究领域:
药理学
·
分析化学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2026
·Vol. 18
·期 2
·310
·
IF 5
Xin Zhang,Di Wang,Yang Wang,Meimei Wang,Juncheng Wang,Yue Sun,Siman Chen,Xinting Qu,Antong Xia,Hongxin Liu,Jihui Wang,Meng Liu
(E)-Flavokawain A (FKA), the primary chalcone constituent of Piper methysticum , exhibits diverse pharmacological properties and holds significant potential for therapeutic development. Objectives : This study aims to investigate the anti-colorectal cancer effects and mechanisms of FKA. Methods : Using AOM/DSS-induced colorectal cancer models in C57 mice, the research examines the impact of different FKA doses, employing 16S rRNA and metabolomics to explore the potential mechanism. Results : The findings indicated that FKA significantly inhibited the progression of colorectal cancer in C57 mice by modulating the composition of the gut microbiota. This modulation involved the suppression of endotoxin secretion by pathogenic bacteria and the concurrent augmentation of beneficial bacteria. Furthermore, in the context of metabolic pathways, FKA regulates lipid metabolism and arachidonic acid metabolism, thereby mitigating the inflammatory transformation associated with colorectal cancer. Conclusions : These findings provide valuable insights supporting the potential of FKA as a viable preventive strategy against CRC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Zijun Li,Siyang Wang,Yanhui Wang,Liyan Shen,Shiyu Hu,Zhouguang Wang,Ruiqin Zhang,Zhen Li
DOP-W-1 was identified as a branched α-glucan from Dendrobium officinale . • DOP-W-1 alleviated DSS-induced colitis and preserved mucosal barrier integrity. • Gut microbiota depletion largely abolished the anti-colitic effect of DOP-W-1. • Fecal microbiota from DOP-W-1-treated mice transferred colitis protection. • DOP-W-1 restored SCFAs and corrected aromatic amino acid-related metabolism. A homogeneous polysaccharide, DOP-W-1, was isolated from Dendrobium officinale and identified as a low-molecular-weight branched α-glucan with a molecular weight of 9.76 kDa, mainly consisting of →4)-α-D-Glcp-(1 → and →4,6)-α-D-Glcp-(1 → residues. This study aimed to determine whether DOP-W-1 protects against dextran sulfate sodium (DSS)-induced colitis through gut microbiota-mediated mechanisms. In DSS-induced colitic mice, DOP-W-1 markedly alleviated disease severity, as shown by reduced body weight loss and disease activity index, restored colon length, improved histopathological injury, preserved mucus barrier integrity, decreased intestinal permeability, and rebalanced inflammatory cytokines. 16S rRNA sequencing revealed that DOP-W-1 selectively reshaped the gut microbiota, characterized by enrichment of Akkermansia and suppression of DSS-associated taxa, including Turicibacter and Alistipes . Importantly, antibiotic-mediated microbiota depletion largely abolished the protective effects of DOP-W-1, whereas fecal microbiota transplantation from DSS + DOP-W-1-treated donor mice reproduced the anti-colitic phenotype, demonstrating that gut microbiota is essential for its protective activity. Functional analysis further showed that DOP-W-1 restored microbial carbohydrate-active enzyme profiles associated with α-glucan utilization. Untargeted metabolomics and short-chain fatty acid analysis indicated that DOP-W-1 corrected aromatic amino acid-related metabolic disturbances, restored D-glucaro-1,4-lactone, and recovered short-chain fatty acid production. Collectively, these findings suggest that DOP-W-1 acts as a microbiota-targeted α-glucan that alleviates experimental colitis by restoring microbial carbohydrate metabolism, metabolic homeostasis, and mucosal barrier function. Download: Download high-res image (164KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Jie Xiong,Jia-jia Yu,Dong-mei Liu,Jia-Juan Wu,Ming-Hua Liang,Jun Tang,Yi-Qian Xu
Polysaccharides have recently garnered interest for their possible biological activity in treating colitis. In this work, we isolated a novel polysaccharide EPS-1 from yogurt, which comprises galactose and glucose (molar ratio = 42.04:57.96) and has a molecular weight of 32.60 kDa on average. The structure characterization revealed that EPS-1 exhibits an amorphous sheet structure with a smooth surface, comprising five distinct glycosidic bonds in its repeating units. The animal experiments showed that EPS-1 might alleviate dextran sulfate sodium-induced colitis by decreasing damage to the intestinal mucosa, intestinal barrier, and inflammatory factor levels, restoring short-chain fatty acids levels, and keeping the balance of intestinal flora. Our findings indicated that EPS-1, which is produced in situ during yogurt fermentation, holds promising potential for the prevention and management of colitis.
研究领域:
食品科学
·
医学
·
肠道微生物学
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Xueming Xu,Yuanfeng Han,Jiali Deng,Shengfeng Wang,Shijie Zhuo,Kai Zhao,Wenhu Zhou
Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu 2+ , although the underlying mechanism of this enhancement remains unclear. In this study, we investigated the mechanistic basis of Cu 2+ -induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate (CuET) complex. CuET exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of action. However, despite its potent activity, CuET suffered from poor solubility and limited permeability, as revealed by our druggability studies. To overcome these intrinsic limitations, we developed a scalable method to prepare CuET nanocrystals (CuET NCs) using a metal coordination-driven self-assembly approach. Pharmacokinetic studies demonstrated that CuET NCs exhibited a 6-fold improvement in bioavailability. Notably, CuET NCs exhibited high biodistribution in the intestine, suggesting their potential application for the treatment of inflammatory bowel diseases (IBDs). To evaluate their therapeutic efficacy in vivo , we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis symptoms. Our findings highlight the discovery of CuET as a potent anti-pyroptotic agent, and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.
研究领域:
药理学
·
纳米技术
·
炎症
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Crohns & Colitis
·
2023
·Vol. 17
·期 8
·1278-1290
·
IF 8
Hu Xiaoming,Jiao Fuxin,Deng Jiali,Zhou Ziheng,Chen Shanghai,Liu Changqin,Liu Zhanju,Guo Feifan
Background and AimsThe incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility.MethodsCISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing.ResultsAgeing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls.ConclusionsCISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.
研究领域:
免疫学
·
胃肠病学
·
分子生物学
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-16
·
IF 4.9
Wang Xiaohu,Shen Chaozhuang,Wang Xingwen,Tang Jin,Wu Zijing,Huang Yunzhe,Shao Wenxin,Geng Kuo,Xie Haitang,Pu Zhichen
Background According to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few.Methods The mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine.Results Mice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1β, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis.Conclusion It seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.
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
危险品化学品经营许可证（带存储）