Antioxidants
·
2025
·Vol. 14
·期 11
·1296
·
IF 6.6
Kang Cheng,Guangbo He,Xiaxia Li,Yuqian Li,Xiaolin Cui,Xuefei Wu,Jau-Shyong Hong,Jie Zhao,Sheng Li,Yanjie Guo
Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders.
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高影响因子
Probiotics and Antimicrobial Proteins
·
2024
·Vol. 17
·期 3
·1523-1535
·
IF 4.4
Wang Minyu,Gao Chongzheng,Lessing Duncan James,Chu Weihua
Colorectal cancer is the third most common cancer in the world today, and studies have shown that the ratio of Candida to Saccharomyces cerevisiae increased, and the abundance of S. cerevisiae in the intestines of patients with colorectal cancer decreased, which suggests that there is an imbalance in the proportion of fungi in the intestines of patients with colorectal cancer. The objective of this study was to screen S. cerevisiae isolate from traditional Chinese fermentation starters and assess its ability to ameliorate dysbiosis and to alleviate the carcinogenic process of azoxymethane/dextran sodium sulfate–induced colorectal cancer in mice model. S. cerevisiae strain SC-2201 was isolated and exhibited probiotic properties, including the ability to survive in an acidic pH environment and in the presence of bile salts in the gastrointestinal tract, as well as antioxidant activities. Oral administration of S. cerevisiae SC-2201 not only alleviated weight loss but also reduced colonic shortening and histological damage in azoxymethane/dextran sodium sulfate–induced colorectal cancer in mice. Furthermore, the administration of S. cerevisiae SC-2201 suppressed the expression of proinflammatory mediators, such as interleukin-1β, interleukin-6, cyclooxygenase-2, vascular endothelial growth factor, nucleotide-binding domain, leucine-rich repeat, and pyrin domain–containing protein 3. Specifically, the analysis of gut bacteriome showed a significant decrease in Bacteroidota and Campylobacterota levels, as well as an increase in Proteobacteria level in the colorectal cancer group, which was alleviated by supplementation with S. cerevisiae SC-2201. The analysis of the mycobiome revealed a significant increase in the levels of Basidiomycota , Apiosordaria , Naganishia , and Taphrina genera in the colorectal cancer group, which were alleviated after supplementation with S. cerevisiae SC-2201. However, the levels of Xenoramularia , Entoloma , and Keissleriella were significantly increased after administration with S. cerevisiae SC-2201. Overall, the findings of this study demonstrate that S. cerevisiae SC-2201 possesses potential probiotic properties and can effectively attenuate the development of colorectal cancer, highlighting its cancer-preventive potential. This is the first report of a S. cerevisiae strain isolated from traditional Chinese fermentation starters which showed good probiotic properties, and mitigated azoxymethane/dextran sodium sulfate–induced colorectal cancer by modulating the gut microbiome and blocking proinflammatory mediators in mice.
研究领域:
微生物学
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肿瘤学
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免疫学
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胃肠病学
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分子生物学
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药理学
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Journal of Materials Chemistry B
·
2026
·
IF 6.2
Wang Zhang,Jingrou Sun,Ying Ou,Jing Zhang,Yilan Bai,Jingxi Hong,Lingchang Meng,Yi Song,Tiepeng Wang,Zhiting Sun,Jing Wu
Ulcerative colitis (UC) is a chronic inflammatory disorder of the intestine characterized by recurrent episodes. Current therapies exhibit limited efficacy and raise safety concerns. This study aimed to enhance the water solubility of the natural compound shikonin and improve its therapeutic efficacy by developing novel metal-phenolic nanoparticles. Zn-shikonin-PEG hybrid nanoparticles (Zn-SHK-PEG NPs) were synthesized by coordinating Zn2+ with shikonin and functionalizing the complex with polyethylene glycol (PEG). Dextran sulfate sodium (DSS)-induced colitis was employed to evaluate the therapeutic potential and mechanisms of the nanoparticles. Treatment with Zn-SHK-PEG NPs markedly alleviated weight loss and colon shortening, decreased the disease activity index (DAI), and reduced histopathological injury. Mechanistic investigations suggested that the nanoparticles reduced histidine decarboxylase (HDC) expression, which was associated with PKM2 regulation, accompanied by decreased histamine (HA) levels and suppressed inflammation. Furthermore, Zn-SHK-PEG NPs altered the gut microbiota composition, including enrichment of Akkermansia muciniphila, which may also contribute to the overall therapeutic effect. In summary, Zn-SHK-PEG NPs ameliorated DSS-induced colitis, and the therapeutic effects were associated with the regulation of the HDC/histamine axis, suppression of inflammatory responses, and modulation of gut microbiota. These findings suggest that Zn-SHK-PEG NPs may represent a potential strategy for ulcerative colitis treatment.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Xiaoyu Wan,Yuanyu Wu,Yanan Sun,Yuxuan Liu,Guoliang Jia
DAS pretreatment protected mice against DSS-induced colitis. • DAS restored tight junctions and suppressed inflammatory injury. • DAS reshaped the gut microbiota toward a protective profile. • DAS increased indole-producing tryptophan metabolites, especially IPA and IAld. Ethnopharmacological relevance Allium sativum L. has a long-standing use in traditional medicine for gastrointestinal disorders. Diallyl sulfide (DAS), a key organosulfur compound derived from garlic, exhibits anti-inflammatory activity; however, its specific role in colitis and the underlying microbiota–metabolite mechanisms remain unresolved. Materials and methods Colitis was induced in mice using DSS following DAS pretreatment. Disease severity, intestinal barrier integrity, inflammation, gut microbiota composition, tryptophan metabolites, AhR signaling, colonic IL-22 levels, and STAT3 phosphorylation were evaluated. Fecal microbiota transplantation (FMT), IPA/IAld supplementation, parallel pharmacodynamic comparisons, and AhR blockade with CH223191 were executed to explore the microbiota–metabolite–host signaling axis. Results DAS pretreatment conferred protection against DSS-induced colitis, evidenced by reduced disease activity, preserved colon length, improved histological injury, suppressed inflammatory responses, and restored tight-junction proteins. DAS modified the gut microbiota and elevated local intestinal levels of IPA and IAld. FMT and IPA/IAld supplementation partially recapitulated the protective phenotype associated with DAS, while combined supplementation of IPA + IAld yielded broader protective effects, nearing the protective outcomes provided by DAS. AhR blockade via CH223191 diminished DAS-mediated protection, characterized by decreases in AhR and Cyp1a1 expression, colonic IL-22 levels, and the p-STAT3/STAT3 ratio. Conclusion DAS pretreatment offers prophylactic protection against DSS-induced colitis by altering the gut microbiota and enhancing local indole-producing tryptophan metabolism, effects mediated at least in part by the AhR/IL-22/STAT3 pathway. Download: Download high-res image (215KB) Download: Download full-size image
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JOURNAL OF FOOD SCIENCE
·
2026
·Vol. 91
·期 9
·e71369
·
IF 4.1
Dongji Hu,Yihui Li,Xiaoyun He
Anthocyanins (ACNs) are natural bioactive compounds with promising anti-colitis potential; however, their poor stability in the gastrointestinal tract limits effective colonic delivery. To address this challenge, this study developed a tannic acid (TA)-based multilayer hydrogel delivery system incorporating ACN-loaded microcapsules. In this system, TA participates in the formation of a mesoporous silica nanoparticles (MSN)-associated TA–Fe 3 + coordination network, which is subsequently embedded within a sodium alginate (SA)/Ca 2 + hydrogel matrix. ACNs were first loaded into MSN, followed by the deposition of a TA–Fe 3 + coating to form microcapsules with an encapsulation efficiency of 87.20%. These microcapsules were subsequently embedded in an SA hydrogel to obtain the final formulation, designated AMTS (ACNs@MSN@TA-Fe 3 + @SA). In vitro simulated digestion showed that AMTS reduced the premature loss of ACNs during gastrointestinal transit and maintained a relatively stable detectable ACN fraction in the digestion medium, supporting the protective role of the carrier and its potential for subsequent delivery to the simulated colonic enzymatic phase. In vivo results showed that AMTS alleviated DSS-induced colonic injury, reduced inflammatory responses, and enhanced intestinal barrier integrity. Compared with free ACNs, AMTS produced more pronounced improvements across several evaluated indices. Collectively, these findings indicate that AMTS represents a promising oral delivery platform to support the potential colonic delivery of ACNs and enhance their protective efficacy in the DSS-induced colitis model, and may offer a practical strategy for the oral delivery of structurally labile natural bioactive compounds.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Qianqian Du,Zhimei Chen,Xian Ma,Yayu Zhang,Yongqiang Fan
Ethnopharmacological relevance Notoginsenoside R1 (NGR1), a primary bioactive constituent of P. notoginseng , has potent anti-inflammatory and immunomodulatory functions, but its role and mechanism in UC remain incompletely understood and warrant further exploration. The global prevalence of ulcerative colitis (UC) is rising steadily, threatening human health. Despite advances in modern therapies, UC treatments remain limited. Aim of the study This work investigated whether NGR1 alleviates DSS-induced colitis by inhibiting the PGAM5-NEK7 interaction and NLRP3 inflammasome activation in macrophages, providing new mechanistic insights and therapeutic targets for UC. Materials and methods UC model was established via 3% DSS administration to assess the protective efficacy of NGR1. Disease activity index (DAI), body weight and colon length were determined to assess disease severity and intestinal injury. HE staining, ELISA and immunofluorescence assays were employed to assess pathological changes in the colon and liver. Macrophages were depleted via tail vein injection of clodronate liposomes. RT-qPCR, ELISA, immunofluorescence and WB were performed to quantify macrophage markers, pro-inflammatory genes and NLRP3 inflammasome-related proteins. In vitro , LPS/ATP-stimulated bone marrow-derived macrophages (BMDMs) demonstrated that NGR1 exerts a potent inhibitory effect on NLRP3 inflammasome activation. After cell treatment, CCK-8, ELISA, RT-qPCR, and WB assays were performed to detect cell viability, inflammatory cytokine levels, and the expression of related genes and proteins. Meanwhile, molecular docking was utilized to verify the interactions among PGAM5, NEK7 and NLRP3. Co-IP in 293T cells overexpressing PGAM5, NEK7 and NLRP3 further verified their interplay. Results Compared with the Model group, NGR1 intervention markedly reduced the DAI scores, ameliorated body weight loss and colon shortening, alleviated colonic and hepatic pathological damage, upregulated the expression of intestinal barrier tight junction proteins (ZO-1, Occludin and Claudin-1), and decreased LPS levels and the release of TNF-α, IL-1β and IL-6 in serum and tissues. Macrophage depletion was observed to markedly abolish protective effects of NGR1, and reduced PGAM5, NEK7, NLRP3, Caspase-1, C-Caspase-1 levels. In vitro , NGR1 inhibited inflammatory factor secretion and NLRP3 inflammasome activation in LPS/ATP-stimulated BMDMs, these effects were partially blocked after PGAM5 or NEK7 gene silencing. Co-IP assays confirmed endogenous interactions between PGAM5, NEK7 and NLRP3. And the molecular docking showed NGR1 could bind to PGAM5, and NGR1 intervention significantly suppressed the expression of the ternary complex formed by the three proteins. Conclusion This study revealed that NGR1 disrupted the PGAM5-NEK7 interaction, restrained NLRP3 inflammasome assembly in macrophages, and relieved colonic damage triggered by DSS, providing a novel target for UC treatment.
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Journal of Environmental Sciences
·
2025
·
IF 6.3
Mengxing Cui,Shilin Chen,Zhihan Zhang,Yongjiang Yu,Yingxi Xu,Ludi Liu,Huan Gao,Xiaoyu Chen,Ziqi Liu,Xue Zhang,Wenke Yuan,Shen Chen,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Yan Liu,Qing Wang
The global incidence of inflammatory bowel disease (IBD) has been escalating. Recent studies have identified co-exposure to polystyrene nanoplastics (PSNP) and triclosan (TCS), two prevalent environmental pollutants, as emerging risk factors for IBD. However, the molecular mechanisms contributing to its deteriorative effect remain elusive. To explore the mechanisms, we conducted an integrative analysis of metagenomic and metabolomic data in a mouse model of colitis induced by dextran sulfate sodium (DSS) following co-exposure to PSNP and TCS. Results demonstrated that co-exposure to PSNP and TCS significantly exacerbated DSS-induced colitis, as evidenced by elevated disease activity indices and pro-inflammatory cytokine levels. Mechanistically, this aggravation correlated with a marked reduction in Akkermansia muciniphila abundance, which was further associated with the disruption of tryptophan metabolism. Specifically, the disruption of this metabolic pathway led to decreased production of two key tryptophan-derived metabolites: indole acetic acid (IAA) and indole acetamide (IAM). In-vitro experiments confirmed that co-exposure to PSNP and TCS inhibited the growth of Akkermansia muciniphila rather than affecting the integrity of intestinal epithelial cells. Additionally, IAA and IAM reduced inflammatory cytokine secretion in THP-1 cells. These findings suggest that the reduction in Akkermansia muciniphila abundance might decrease the production of IAA and IAM by disrupting tryptophan metabolism. This disruption ultimately contributes to the inflammatory response induced by co-exposure to PSNP and TCS. Our study offers a novel insight into microbiota-host interactions and potential therapeutic targets for intestinal disease.
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Foods
·
2025
·Vol. 14
·期 13
·2345
·
IF 5.1
Yifei Guo,Xinyu Yu,Rongrong He,Jianfei Pei,Haiming Chen,Weijun Chen
Ferulic acid (FA) exhibits beneficial properties in ulcerative colitis (UC) pathogenesis, while sensitivity to the environment and enzymes limits its use in UC therapy. Therefore, this study aims to develop a colon-targeted nanocomplex delivery system using FA and investigate its protective effects and underlying regulatory mechanisms in UC mice. A novel Zein/FA–pectin (PEC)/chitosan (CS) nanocomplex was successfully fabricated in this study. Through systematic adjustment of the PEC/CS-to-Zein/FA ratio, optimal encapsulation efficiency (60.1%) and loading capacity (26.2%) were achieved. The characterized data indicated that hydrogen bonds, electrostatic interactions, and hydrophobic forces were the main driving forces maintaining the formation of the nanocomplexes, accompanied by alterations in the secondary structure of Zein. The Zein/FA–PEC/CS nanocomplexes demonstrated excellent thermal/storage particle size stability and exhibited both protective and sustained-release effects of FA during simulated gastrointestinal digestion. Furthermore, the results demonstrated that the nanocomplexes potentially alleviate UC by regulating inflammatory cytokines, oxidative stress, and gut microbiota. Compared to unencapsulated FA, the nanocomplexes have a better effect on alleviating UC symptoms. In summary, Zein/FA–PEC/CS nanocomplexes have promising prospects in alleviating colitis in UC mice.
研究领域:
生物医学
·
药剂学
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食品科学
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免疫学
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Journal of Ginseng Research
·
2025
·
IF 5.6
Ji Zhang,Jing Xie,Zhiqiang Niu,Long You,Yanan Liu,Rui Guo,Guigui Yang,Ziliang He,Ting Shen,Honggang Wang,Qi Yan,Weicheng Hu
Background Ginsenoside Rg2 (G-Rg2), a major active compound of Panax ginseng , exhibits a wide range of pharmacological properties, including anticancer, antioxidant and neuroprotective effects. However, the mechanisms by which G-Rg2 mitigates ulcerative colitis (UC) have not been clearly elucidated. Aims In the present study, we aimed to elucidate the underlying mechanisms by which G-Rg2 mitigated UC. Methods In this study, we investigated the efficacy of G-Rg2 in ameliorating dextran sulfate sodium (DSS)-induced UC and its potential mechanisms using a DSS-induced UC mouse model and Lipopolysaccharides (LPS)/ nigericin (Nig)-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation on immortalized bone marrow-derived macrophages (iBMDMs). Results Oral administration of G-Rg2 at doses of 10 and 20 mg/kg significantly mitigated weight loss, normalized food and water intake, and improved colon histopathology in DSS-induced UC mice. G-Rg2 also restored mRNA expression levels of occludin, claudin-3, zona occluden (ZO)-1 and mucin 2, thereby enhancing intestinal barrier integrity. G-Rg2 significantly suppressed the nuclear translocation of p65, the subunit of nuclear factor kappa-B (NF-κB), as well as downregulated NLRP3, cleaved IL-1β and caspase1 p20 expression induced by LPS/Nig in iBMDMs. Conclusion G-Rg2 effectively reduced colon inflammation in DSS-induced UC mice and diminishes inflammatory responses under LPS/Nig conditions by regulating NF-κB/NLRP3 pathway, thereby inhibiting NLRP3 inflammasome activation, which may serve as a potent therapeutic agent for UC.
研究领域:
药理学
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免疫学
·
消化系统疾病
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Antioxidants
·
2022
·Vol. 11
·期 12
·2406
·
IF 7.675
Xiang-Rong Cheng,Bu-Tao Yu,Jie Song,Jia-Hui Ma,Yu-Yao Chen,Chen-Xi Zhang,Piao-Han Tu,Mitchell N. Muskat,Ze-Gang Zhu
Food-derived electrophilic compounds (FECs) are small molecules with electrophilic groups with potential cytoprotective effects. This study investigated the differential effects of six prevalent FECs on colitis in dextran sodium sulfate (DSS)-induced mice and the underlying relationship with molecular characteristics. Fumaric acid (FMA), isoliquiritigenin (ISO), cinnamaldehyde (CA), ferulic acid (FA), sulforaphane (SFN), and chlorogenic acid (CGA) exhibited varying improvements in colitis on clinical signs, colonic histopathology, inflammatory and oxidative indicators, and Nrf2 pathway in a sequence of SFN, ISO > FA, CA > FMA, CGA. Representative molecular characteristics of the “penetration-affinity–covalent binding” procedure, logPvalue, Keap1 affinity energy, and electrophilic index of FECs were theoretically calculated, among which logPvalue revealed a strong correlation with colitis improvements, which was related to the expression of Nrf2 and its downstream proteins. Above all, SFN and ISO possessed high logPvalues and effectively improving DSS-induced colitis by activating the Keap1–Nrf2 pathway to alleviate oxidative stress and inflammatory responses.Keywords:electrophilic compound;colitis;molecular characteristic;logP
研究领域:
药理学
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免疫学
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分子生物学
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Frontiers in Nutrition
·
2022
·
IF 6.59
He Ke-Jie,Dong Jia-Hui,Ouyang Xiao-Mei,Huo Ya-Ni,Cheng Xiao-Shen,Lin Ying,Li Yue,Gong Guoyu,Liu Jingjing,Ren Jian-Lin,Guleng Bayasi
Background and aims: Inflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.Methods: Acute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg−1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.Results: GML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.Conclusions: We showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.
研究领域:
免疫学
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胃肠病学
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微生物学
·
药理学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Zhaoxia Tang,Jiali Luo,Yahya Faqir,Yu Zhang,Wenqian Xue,Hongmei Zhao,Ali Murad Jakhar,Chengjia Tan,Jiahua Ma
Berberine hydrochloride (BH) has long been known for its therapeutic efficacy. In the present study, we aimed to treat mice with colitis using dung beetle chitosan (DCS) -transported BH. To achieve this, BH-loaded DCS/sodium alginate microspheres (SA-DCS-BH) were prepared. The SA-DCS-BH was characterized using SEM, DLS , FT-IR, and XRD, then was used for administration and anti-inflammatory examination in mice. SEM and DLS confirmed the surface morphology of the microspheres, and the particle size was relatively uniform. FT-IR and XRD results confirmed that BH was successfully loaded. In vitro and in vivo studies showed that SA-DCS-BH had slow-release ability. After treatment with SA-DCS-BH, DAI was significantly reduced, colon weight and length increased, spleen length and weight reduced, concentrations of pro-inflammatory cytokines in colonic tissues were reduced, and gut microbiota species abundance was modulated. In addition, this study found a correlation between specific microbes and colitis indicators, Muribaculaceae showed sequential growth after receiving BH, SA-CS-BH, and SA-DCS-BH treatments, respectively. It was concluded that SA-DCS-BH effectively delivered the BH to the intestine with slow-release ability and exhibited anti-inflammatory effects by immune response. Compared to commercial chitosan, DCS has potential for modulating intestinal microorganisms and more suitable carrier for intestinal drug delivery systems.
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