BIOCHEMICAL PHARMACOLOGY
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2022
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IF 6.1
Chao Liu,Yuhong Jiang,Ganglei Liu,Zhushu Guo,Qianqian Jin,Dongju Long,Weihan Zhou,Ke Qian,Hua Zhao,Kuijie Liu
Background Chronic inflammation of the gastrointestinal tract is a feature of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Targeting inflammatory signaling represents promising strategy for IBD treatment regimens. Methods Dextran sulfate sodium (DSS)-induced colitis model was established in mice. Histopathological examinations were conducted by H&E staining and IHC staining. IL-1β, IL-10, and TNF-α were tested by ELISA kits. TargetScan was used to predict miRNAs that target PPARGC1A and luciferase activity assay was performed to validate the predicted binding. Results DSS-induced acute colitis model was successfully established in mice; photodynamic therapy (PDT) treatment partially improved DSS-induced colonic damages and cell inflammation. Microarray assays and integrative bioinformatics analysis identified PPARG coactivator 1 alpha (PPARGC1A) as a significantly differentially-expressed gene in PDT-treated IBD compared with non-treated IBD. PPARGC1A expression was downregulated in IBD clinical samples, DSS-induced colitis mice colons, and DSS-stimulated colonic epithelial cells, whereas partially upregulated by PDT treatment in DSS-stimulated cells. Single DSS stimulation significantly promoted cellular inflammation; PDT partially attenuated, whereas sh-PPARGC1A transduction further enhanced DSS effects on cancer cell inflammation. In colitis mice, DSS decreased PPRA-α and PPRA-γ proteins in mice colons; the in vivo effects of DSS were partially attenuated by PDT treatment, whereas amplified by sh-PPARGC1A transduction. Upstream miR-301a-3p targeted and inhibited PPARGC1A expression. Conclusions Collectively, PPARGC1A, which is downregulated in DSS-induced acute colitis and DSS-stimulated colonic epithelial cells, could be upregulated by PDT treatment. PPARGC1A knockdown could attenuate PDT therapeutic effects on DSS-induced acute colitis and DSS-stimulated colonic epithelial cells.
研究领域:
胃肠病学
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免疫学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2021
·
IF 9.147
Dongmei Wu,Shiguo Chen,Xingqian Ye,Shokouh Ahmadi,Weiwei Hu,Chengxiao Yu,Kai Zhu,Huan Cheng,Robert J. Linhardt,Qiaojun He
Administration of pectic polysaccharides is a therapeutic strategy in the management of gut inflammation. However, the knowledge about the effects of different dietary sources and structure are missing. This study explored the protective effects of six different pectic polysaccharides from Goji berry (G), dragon fruit (D), lemon (L), pomelo (P), potato (T) and raspberry (R) in dextran sulfate sodium (DSS)-induced colitis mice. D mainly contained rhamnogalacturonan (RG) backbone; L had high amount of arabinan sidechains; P was a high-esterified homogalacturonan (HG) pectic polysaccharide; the primary domain in T was galactan sidechains; R and G had the composition of arabinan: galactan: RG: HG = 19: 28: 15: 22 and 36: 17: 21: 14. Our results suggested that G and R were the most effective in alleviating colitis via alleviating tissue damage, promoting the index of immune organs, suppressing the production of TNF-α, IL-1β and IL-17, improving antioxidant status and promoting the total amount of SCFAs. Similarly, the administration of L alleviated colitis mainly by increasing the fermentation products without changes in the composition pattern of SCFAs. The secretion of IL-6 might be suppressed by pectic polysaccharides containing high amount of arabinan sidechains, while anti-inflammatory cytokines and intestinal barrier function tend to be regulated by pectic polysaccharides rich in galactan. In conclusion, pectic polysaccharide containing diversified structural domains (homogeneous proportion of HG, RG, arabinan, and galactan) might be the most effective in alleviating gut inflammation. This unprecedented report revealed the anti-inflammatory effects of different pectic polysaccharides, which was critical for the reasonable selection of dietary fiber to prevent gut inflammation.
研究领域:
营养学
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免疫学
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胃肠病学
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药理学
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产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Ruoqing Zeng,Meimiao Fang,Ancheng Shen,Xiaolei Chai,Yumiao Zhao,Mingyao Liu,Lingfeng Zhu,Weiwei Rui,Bo Feng,Liang Hong,Chunyong Ding,Zilan Song,Weiqiang Lu,Ao Zhang
Accumulating evidence has demonstrated a critical pathological role of oxysterol receptor GPR183 in various inflammatory and autoimmune diseases, including inflammatory bowel disease (IBD). However, the currently reported GPR183 antagonists are very limited and not qualified for in vivo studies due to their inferior druglike properties. Herein, we conducted a structural elaboration focusing on improving its PK and safety profile based on a reference antagonist NIBR189. Of note, compound 33, bearing an aminobenzothiazole motif, exhibited reduced hERG inhibition, improved PK properties, and robust antagonistic activity (IC50 = 0.82 nM) with high selectivity against GPR183. Moreover, compound 33 displayed strong in vitro antimigration and anti-inflammatory activity in monocytes. Oral administration of compound 33 effectively improved the pathological symptoms of DSS-induced experimental colitis. All of these findings demonstrate that compound 33 is a novel and promising GPR183 antagonist suitable for further investigation to treat IBD.
研究领域:
药理学
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免疫学
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药物化学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
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IF 6.5
Xinwen Li,Lin Cao,Jianmin Li,Zhengyang Li,Hongyu Ma,Shifeng Cheng,Hongyi Xu,Yang Zhao
Background Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with no clinical cure. Excessive production of reactive oxygen species (ROS) at the inflammatory sites leads to the onset and progression of IBD. And the current non-invasive imaging methods are not ideal for the diagnosis and monitoring of IBD.Methods Herein, we developed inulin (IN)-coated cerium oxide nanoparticles (CeO2@IN NPs) for treatment and monitoring of IBD guided by computed tomography (CT). The physicochemical properties, ROS scavenging ability and CT imaging capabilities of CeO2@IN were investigated in vitro. Moreover, the therapeutic and targeted inflammation imaging effects of CeO2@IN were validated in dextran sulfate sodium (DSS)-induced colitis model.Results CeO2@IN with catalase (CAT) and superoxide dismutase (SOD) capabilities effectively scavenged ROS, thus protecting the cells against oxidative stress. In colitis model mice, orally administered CeO2@IN successfully traversed the gastrointestinal tract to reach the colon under the protection of IN, and effectively reduced intestinal inflammation, thereby maintaining the intestinal epithelial integrity. Notably, CeO2@IN performed better than conventional CT contrast agents for gastrointestinal tract imaging, particularly in detecting the inflamed areas in the colon. In addition, CeO2@IN exhibited excellent biocompatibility in vitro and in vivo.Conclusion The study provided a novel integrated diagnostic and therapeutic tool for the treatment and monitoring of IBD, presenting great potential as a clinical application for IBD.
研究领域:
医学
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生物材料学
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影像学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Tong Zhang,Chen Wang,Ting Du,Haoyu Sun,Yaru Han,Shuo Shi,Jianlong Wang,Wentao Zhang
Probiotics offer a promising strategy to address the dysfunction of the intestinal mucosal barrier and dysregulation of the gut microbiota in inflammatory bowel disease (IBD). However, the low viability and poor adhesion of probiotics in complex gastrointestinal environments pose significant challenges. To tackle these issues, we designed a specialized protective nano-coating (PDA@CeO 2 ) using biointerfacial phenolic assembly combined with nanozymes for Bifidobacterium bifidum (B.B.). Characteristic peaks of CeO 2 nanoparticles were detected on B.B. via XRD analysis, while SEM and TEM images confirmed the successful attachment of CeO 2 nanoparticles to the probiotic surface. The nano-coating (PDA@CeO 2 ) simultaneously provides B.B. with high adhesion in the intestine, strong tolerance in complex gastrointestinal environments, and the ability to scavenge excess reactive oxygen species (ROS) due to its excellent mucoadhesive ability and high nanozyme activity. Specifically, the protection provided by nano-coating against simulated gastric fluid (SGF, pH 1.2) resulted in cell survival rates approximately 9.4 times higher than those of unprotected B.B. after 1 h of exposure. In IBD mouse models, the combination of PDA@CeO 2 and B.B. demonstrated excellent therapeutic effects, promoting gut barrier repair. Additionally, an increase in Muribaculaceae and Prevotellaceae_UCG-001 and a decrease in Desulfovibrionaceae reshaped the intestinal flora, reducing recurrence. This study highlights the potential of enhancing probiotic functionality through targeted design of protective nano-coatings for IBD therapy.
研究领域:
生物医学工程
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Jinfan Yang,Ning Shang,Zhengqing Li,Ji Xu,Xin Zhou,Hui Zhou,Wen Luo,Peng Xu,Yucheng Zhou,Xueru Sheng,Zheng Zhu,Mingzhen Zhang,Xiaojun Ma,Mingqian Tan,Hao Wu
Oral formulation is the ideal treatment method for inflammatory bowel disease (IBD) therapy, but the mucosal damage and diarrhea symptoms impede the drug retention around the inflammatory region, severely limiting IBD therapeutic efficacy. To address this, an oral astaxanthin (Ast) precise delivery formulation is developed with the selective Ast anchoring around the inflammatory region by the novel lactoferrin (LF)-responsive flocculation. This formulation also heightens the apparent solubility of Ast with the minimized edible safety risks for the edible raw materials. For in vivo IBD therapy, the precise delivery formulation exhibits remarkable outcomes, including a significant increase in colon length and a 100% survival rate. Furthermore, it is verified that the mechanism of treatment is primarily attributed to the improved immunoregulation, epithelial repair, and gut microbiota remodeling after the LF-responsive flocculation. This effective inflammatory-responsive delivery design is instructive and valuable to develop more precise delivery systems for IBD therapy.
研究领域:
药剂学
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生物医学
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消化系统疾病
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产品关联
DOI
PubMed
高影响因子
Journal of Future Foods
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2026
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IF 7.2
Linlin Hao,Yinxue Liu,Yisuo Liu,Lu Jiang,Ignatius Man-Yau Szeto,Tongjie Liu,Huaxi Yi
Probiotics represents a significant strategy for managing inflammatory bowel disease (IBD), however, the inflammatory gut microenvironment rich in reactive oxygen species (ROS) compromises the viability and colonization of probiotics. Here, we innovatively developed a ROS-responsive probiotic delivery system based on milk exosomes (mExo@DSPE-PEG-PBA@AKK). The ROS-sensitive borate ester bond in mExo@DSPE-PEG-PBA@AKK underwent oxidation and cleavage at inflammatory sites, which simultaneously scavenged excessive ROS and achieved targeted release of the probiotics. Consequently, mExo@DSPE-PEG-PBA@AKK exhibited enhanced activity and prolonged retention within the inflamed intestine. In dextran sulfate sodium (DSS)-induced colitis mice, mExo@DSPE-PEG-PBA@AKK showed superior therapeutic efficacy compared to treatment with milk exosomes or probiotics alone. Furthermore, mExo@DSPE-PEG-PBA@AKK treatment reduced pro-inflammatory factor levels, restored intestinal barrier integrity, and effectively modulated the abundance and diversity of the gut microbiota in DSS-induced mice. The proposed mExo@DSPE-PEG-PBA@AKK system incorporates multiple functions including probiotic protection, delivery, and targeted release, offering a novel “clear-release-regulate” therapeutic approach for the treatment of IBD.
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产品关联
DOI
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
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IF 3.6
Chen Xiaohui,Lin Shengrong,Liang Yunbang,Xue Xiaomin,Yasen Miersalijiang
Shikonin is a natural product with antioxidant and anti-inflammatory activities. The biological activity of shikonin is still not fully understood, as well as its association with innate immunity and immune and inflammatory bowel disease (IBD) in humans. In this study, the toxicity of shikonin on Raw264.7 cells was assayed by MTT, and polarization of inflammatory macrophages was determined by flow cytometry. The results showed that shikonin can inhibit the polarization of macrophages towards M1 type and significantly inhibited the production of NO in the concentration range of 0.5–1 μM. In addition, after treatment with shikonin, the production of IL-1β and TNF-α was significantly decreased. After shikonin administration, the body weight loss and decrease of colon length were significantly suppressed in DSS-treated colitis C57BL/6 mice. The pro-inflammatory cytokines TNF-α and IL-1β in colonic homogenate were significantly decreased. Shikonin treatment resulted in a notable improvement in the histopathological manifestations in DSS-treated animals at 25/50 mg/kg. Meanwhile, we found that shikonin can regulate differentiation of T helper 17 cell (Th17)/regulatory T cell (Treg), thereby regulating the balance of Th17/Treg cells and exerting an anti-inflammatory effect in IBD animal models. In conclusion, we found that shikonin protects against DSS-induced acute colitis by, among other things, reducing immune cell infiltration, polarizing macrophages, and regulating Th17/Treg differentiation, as well as by downregulating the release of inflammatory cytokines. These findings showed that shikonin can improve inflammation by affecting macrophage polarization. Our experimental data provide experimental evidence and theory basis for research on anti-inflammatory effects for the shikonin as health or functional food. Graphical Abstract
研究领域:
免疫学
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药理学
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消化病学
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产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Translation
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2026
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IF 9.8
Yimin Pi,Haodong Zhu,Jian Xie,Furui Tang,Zhuoya Wang,Li Liu,Yuchun Zhong,Zhidong He,Tian Liu,Jiacheng Zheng,Yuwen Tang,Jun Luo,Cihua Zheng
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder frequently accompanied by extraintestinal complications such as bone loss, yet effective treatment options remain elusive. In this study, we investigated whether hesperetin mitigates colitis-associated bone loss by modulating the “gut–bone axis.” Using a DSS-induced mouse model of chronic colitis, we found that hesperetin significantly reduced intestinal inflammation, restored mucosal barrier integrity, and suppressed serum inflammatory cytokines. Furthermore, hesperetin effectively alleviated DSS-induced bone microstructure damage, promoted the expression of ALP, Runx2, OCN, and inhibited NFATc1 and CTSK. Fecal microbiota transplantation experiments further confirmed that the intestinal microbiota from hesperetin-treated group attenuated intestinal inflammation and bone loss. 16S rRNA sequencing and metabolomics revealed that hesperetin enriched Akkermansia muciniphila ( A. muciniphila ) and increased the tryptophan metabolite 3-indoleacrylic acid (IDA). Supplementation with A. muciniphila or IDA alone simulated the therapeutic benefits of hesperetin. Furthermore, RNA-seq revealed that hesperetin regulated bone metabolism-related gene expression by ECM-receptor interaction and PI3K-AKT signaling, while inhibiting the NOD-like receptor pathway. In conclusion, hesperetin mitigates intestinal inflammation and bone homeostasis imbalance by reshaping the gut microbiota, enriching A. muciniphila, and promoting IDA production, thus providing new insights into potential therapies for IBD-related bone loss. Download: Download high-res image (369KB) Download: Download full-size image
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ganglin Wang,Ziwei Wang,Lin Liu,Yejing Zhu,Jiali Zhong,Jiayi Zhang,Lingling Wang,Chenguo Zheng,Wei Li
Humic acid (HA), a complex organic substance naturally present in soil, peat, and coal, is traditionally referred to as the extract of "Wujinshi" (乌金石) in Chinese medicine. It is renowned for its potent anti-inflammatory, analgesic, and blood circulation-promoting properties. However, its mechanisms and delivery methods require further exploration. We developed BiHANs, a novel nanoparticle combining bismuth and HA, which exhibits excellent biocompatibility and anti-inflammatory effects in vitro . Orally administered BiHANs accumulate at inflammatory sites in the colon of DSS-induced IBD mice, as confirmed by CT imaging, and prolong intestinal retention. They significantly alleviate acute and chronic intestinal damage by suppressing inflammatory responses, modulating gut microbiota, and targeting macrophage mitochondria to inhibit NF-κB-driven cytokine production. BiHANs also maintain mitochondrial homeostasis and exert antioxidative effects. Furthermore, their performance in CT imaging highlights potential as a theranostic agent. This study demonstrates BiHANs as a promising platform for targeted IBD therapy and diagnosis, combining anti-inflammatory efficacy with imaging capabilities.
研究领域:
药理学
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纳米医学
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消化系统疾病
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Shiwen Gong,Wentao Ma,Die Hu,Haixing Xu,Binbin Li,Xinyu Wang
Inflammatory bowel disease ( IBD) is an idiopathic, lifelong, and devastating chronic inflammatory disease of the gastrointestinal tract. Berberine, an alkaloid extracted from the Chinese herb Huanglian, is a pharmaceutical ingredient with antibacterial, anti-inflammatory, and antiviral pharmacological effects in Chinese medicine. However, direct administration of berberine requires high doses due to its low bioavailability and high waste in the stomach. In this study, we prepared berberine-loaded pH-responsive Eudragit® FS 30D-attapulgite (FS-ATT) microspheres for the targeted treatment of colitis. The microspheres had pH-responsive release behavior, with minimal berberine release (about 5.97%) in simulated gastric fluid and high berberine release in simulated colonic fluid (about 69.27%). In addition, it was revealed by in vivo biological evaluations that, compared with drugs in an equivalent solution form taken orally, a significant improvement in IBD symptoms was observed after oral administration of drug-loaded FS-ATT microspheres, leading to an increase in the diversity of intestinal microbiota, inhibition of inflammatory cytokines, and enhanced therapeutic effects of berberine. The pH-responsive FS-ATT microspheres could offer a promising drug delivery platform for managing and treating many gastrointestinal diseases.
研究领域:
药剂学
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生物医学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 7
·3946-3956
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IF 6.317
Zhe Wang,Chunhai Li,Xi He,Kang Xu,Zhipeng Xue,Ting Wang,Zhenshang Xu,Xinli Liu
The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.
研究领域:
药理学
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免疫学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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