PHYTOMEDICINE
·
2021
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IF 5.34
Yajie Cai,Bing Xu,Fei Zhou,Jianzhi Wu,Shuo Li,Qi Zheng,Yajing Li,Xiaojiaoyang Li,Feng Gao,Shifen Dong,Runping Liu
Background Ulcerative colitis (UC) is a chronic relapsing inflammatory disease that markedly elevates the risk of colon cancers and results in disability. The disrupted immune homeostasis has been recognized as a predominant player in the pathogenesis of UC. However, the overall remission rate of current therapies based on immunoregulation is still unsatisfactory. Si-Ni-San (SNS) has been found effective in relieving UC through thousands of years of clinical practice, yet the specific mechanisms of the protective effect of SNS were not fully elucidated. Purpose We aim to investigate the therapeutic effects of SNS against the development of chronic colitis and the underlying mechanisms. Methods We established a DSS-induced chronic experimental colitis mouse model to evaluate the effect of SNS. RNA-sequencing, bioinformatic analysis, and in vitro studies were performed to investigate the underlying mechanisms. Results Our data demonstrated that SNS significantly ameliorated chronic experimental colitis via inhibiting the expression of genes associated with inflammatory responses. Interestingly, SNS significantly suppressed DSS-induced type I interferon (IFN) responses instead of directly downregulating the production of pro-inflammatory cytokines, such as Il-6. In vitro study further found that SNS selectively inhibited STING and RIG-I pathway-induced type I IFN responses by modulating TBK1- and IRF3-dependent signaling transduction. SNS also suppressed the expression of IFN-stimulated genes by directly inhibiting STAT1 and STAT2 activation. Conclusion Our study not only provides novel insights into the pathogenic role of type I IFN responses in colitis but also suggested that SNS or bioactive compounds derived from SNS may serve as novel therapeutic strategies for the treatment of UC via interfering type I IFN-mediated inflammation.
研究领域:
药理学
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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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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Zhiran Ju,Junde Xu,Keshuang Tang,Fener Chen
COX-2/NLPR3-targeted therapy might be beneficial for the inflammation diseases. To discover novel anti-inflammatory compounds with favorable safety profiles, three new series of non-carboxylic diclofenac analogues bearing various ring systems, such as oxadiazoles 4a - 4w , triazoles 6a - 6m , and cyclic imides 7a and 7b , were synthesized. The synthesized analogues were evaluated for their inhibitory activity against COX-2 enzyme. Among them, compound 6k exhibited potent selective COX-2 inhibition (IC 50 = 1.53 μM; selectivity ((IC 50 (COX-1)/IC 50 (COX-2) = 17.19). Treatment with compound 6k effectively suppressed the NF-κB/NLRP3 signaling pathway, resulting in reduced expression of pro-inflammatory factors. The in vivo ulcerative colitis assay demonstrated that compound 6k significantly ameliorated histological damages and showed strong protection against DSS-induced acute colitis. The collected results indicated that compound 6k displays anti-inflammatory activity through COX-2/NLRP3 inhibition. Therefore, compound 6k represents a promising candidate for further development as a new lead compound with reduced colitis side effects.
研究领域:
药理学
·
药物化学
·
炎症研究
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Yiting Luo,Jin Wu,Yingchao Liu,Yan Shen,Fangyuan Zhu,Jiaqian Wu,Yuyao Hu
Purpose Shaoyao decoction (SYD) is a traditional Chinese medicine used to treat ulcerative colitis (UC). The exact mechanism of action of SYD in UC treatment is still unclear. Here, we examined the therapeutic effects of SYD in mice with dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanism. Methods The experimental group was divided into normal control, UC, and SYD treatment groups. The UC model of C57BL/6 mice was induced using 3% (w/v) DSS for 7 days. SYD was orally administered for 7 days. The proximal and distal colonic metabolic profiles were detected using quadrupole-time-of-flight mass spectrometry-based untargeted metabolomics. Results SYD significantly increased weight, reduced disease activity index scores, and ameliorated colon length shortening and pathological damage in mice. In the distal colon, SYD increased the abundance of phosphatidic acid and lysophosphatidylethanolamine and decreased the abundance of lactosylceramide, erythrodiol 3-palmitate, and lysophosphatidylcholine. In the proximal colon, SYD increased the abundance of palmitic acid, cyclonormammein, monoacylglyceride, 13S-hydroxyoctadecadienoic acid, and ceanothine C and decreased the abundance of tetracosahexaenoic acid, phosphatidylserine, and diglyceride. Conclusion Our findings revealed that SYD could alleviate UC by regulating metabolic dysfunction, which provides a reference for further studies on SYD.
研究领域:
中药学
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代谢组学
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消化系统疾病
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2023
·
IF 3.8
Jiaxi Chen,Mengyue Pan,Jingjie Wang,Mengling Zhang,Mingmei Feng,Xiaoming Chai,Qi Zhang,Yang Sun
Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5′-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography–mass spectrometry (GC–MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.
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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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Cellular & Molecular Immunology
·
2023
·
IF 24.1
Luo Ya,Liu Cheng,Luo Yuan,Zhang Xianglian,Li Jing,Hu Changjiang,Yang Shiming
Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4 + T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for 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
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药理学
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产品关联
DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2022
·
IF 3.247
Shengwei Li,Guangqing Feng,Min Zhang,Xing Zhang,Jihong Lu,Chenyahui Feng,Fangshi Zhu
Objective: Due to its well-known anti-inflammatory property, oxymatrine (OMT) has received more attention on the aspect of treating ulcerative colitis. Although efforts have been undertaken to understand the therapeutic mechanism of OMT on ulcerative colitis (UC), the remedial principle is still ambiguous. Numerous studies have shown that TLR9/Myd88/NF-κB signal pathway played a key role in the pathogenesis of UC. Moreover, TLR9/Myd88/NF-κB signal pathway is a part of the most important pathways for regulating the immune response.Methods: We explored the influence of OMT with different dosages on UC by establishing a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Moreover, the participation of TLR9/Myd88/NF-κB signal pathway and whether OMT protects against UC though targeting this pathway are further studied.Results: Our data revealed that OMT could significantly relieve the symptom of TNBS-induced colitis in rats by reactivating the tight junction protein and, more important, by inhibiting the activation of TLR9/Myd88/NF-κB pathway and protein expression levels of its downstream inflammatory factors.Conclusion: OMT could relieve colitis in rat models by impacting tight junction proteins’ TLR9/Myd88/NF-κB signal pathways and activity.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Yeye Hu,Ziliang He,Ji Zhang,Chaohua Zhang,Yanting Wang,Wei Zhang,Fenglun Zhang,Weiming Zhang,Fenglin Gu,Weicheng Hu
Background Piper nigrum essential oil (PnEO) possesses pleasant aroma, unique flavor, and various bioactivities; however, its role against colitis remains unclear. Purpose In this study, we investigated the role of PnEO in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)–induced colitis. Methods Initially, we identified and quantified the components of PnEO by gas chromatography-mass spectrometry (GC–MS). Subsequently, we investigated the protective role of PnEO (50 and 200 mg/kg) in DSS-induced colitis in mice by evaluating disease activity index (DAI) scores and colon length, and performing histological analyses. Eyeball blood was collected and cytokines were determined using ELISA kits. The anti-inflammatory mechanisms of PnEO were analyzed by western blot (WB) and immunohistochemistry (IHC). The intestinal barrier function was evaluated according to tight junction (TJ) protein mRNA levels. We used 16S rRNA gene sequencing to analyze the intestinal microflora of mouse cecal contents. Results Supplementation with PnEO (50 and 200 mg/kg) increased colon length and improved colon histopathology . PnEO regulated inflammatory responses by downregulating TLR4/MAPKs activation, thereby reducing the release of cytokines and mediators. Moreover, it also protected the intestinal barrier through enhancing the expression of claudin-1, claudin-3, occludin , ZO-1, and mucin 2 . 16S rRNA gene sequencing revealed that PnEO (200 mg/kg) decreased the abundance of Akkermansia in the gut microbiome . Conclusion PnEO treatment (50 and 200 mg/kg) relieved DSS-induced colitis by inhibiting TLR4/MAPK pathway and protecting intestinal barrier, and high-dose PnEO exhibited better effects. Moreover, PnEO (200 mg/kg) regulated key compositions of the gut microbiome, which indicated that it had therapeutic potential for sustaining gut health to lower the risk of colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
·
2019
·
IF 2.18
Wei Chen,Jing Zhang,Chen Li,Quan Pan,Jingtong Wu,Lina Fan,Chunyan Chen,Xiaoqing Huang,Fei Teng,Jinshui Zhu
Animal models play critical roles in exploring the pathogenesis of human diseases and designing novel therapeutic schemes. Acute experimental colitis (AEC) models have been reported to be established in mice principally by oral administration of dextran sulfate sodium (DSS). However, little knowledge is known about whether DSS can be used to induce the acute experimental enteritis (AEE). In this study, different concentrations of DSS (0%, 2%, 3%, and 5%) were used to induce AEC and AEE models in two cohorts. After the establishment of these two models, the symptoms of the mice induced by DSS were noted, the length and average weight of each colon and small intestine were measured, and hematoxylin and eosin (HE) staining was conducted for assessing the inflammatory infiltration in these models. Generally, the comparison of the inflammatory scoring between AEC and AEE models was analyzed. As a consequence, we found that, the mice with 2%–5% DSS administration in a week could develop into AEC models in two cohorts and AEE models in one cohort, followed by the signs of diarrhea, gross rectal bleeding, weight loss of the body, and shortened colon and intestine length, as compared with the control group. HE staining showed that the inflammatory scoring was dramatically increased by 3%–5% DSS in AEC models in two cohorts but slightly elevated in AEE models in one cohort. Meanwhile, as compared with the severe AEC models, the extent of inflammatory infiltration induced by 3%–5% DSS in AEE models was much milder. In conclusion, oral administration of 3%–5% DSS is a good inducer of AEC models, but not AEE models.
研究领域:
免疫学
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胃肠病学
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药理学
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
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IF 3.712
Haihua Zhang,Wuying Lang,Sufen Li,Chao Xu,Xiumin Wang,Yunyu Li,Zhiqiang Zhang,Tonglei Wu,Minshan Feng
Objective Corynoline is an active substance extracted from Corydalis bungeana Turcz and exerts a therapeutic effect in multiple diseases by alleviating inflammatory response. The present study sought to elucidate the role of corynoline in ulcerative colitis (UC).Methods The experimental colitis models were induced in BALB/c mice via receiving a drinking water supplemented with 3.5% (I) dextran sulfate sodium (DSS) ad libitum for 7 days.Results Corynoline administration inhibited body weight loss, colon shortening, disease activity index and colonic pathomorphological changes in DSS-treated mice. Besides, corynoline down-regulated the levels of pro-inflammatory interleukin (IL)-1β, IL-6 and tumor necrosis factor Alpha (TNF-α), as well as decreased myeloperoxidase (MPO) activity in the colon of DSS-treated mice. In addition, severe oxidative stress in the colonic tissues of DSS-treated was mitigated by corynoline treatment. However, these beneficial effects were reversed by a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 intervention. Further evidence confirmed that corynoline promoted Nrf2 nuclear migration and heme oxygenase-1 gene expression in the colonic tissues of UC mice. Besides, corynoline treatment restrained colonic nuclear factor-kappa B (NF-κB) activation as proved by the decrease in phosphorylation and nuclear translocation of NF-κB.Conclusions Corynoline ameliorates DSS-induced mouse colitis, which may provide a promising therapeutic strategy for UC treatment.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Therapeutic Advances in Gastroenterology
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2021
·
IF 4.409
Fenghua Xu,Yi Cheng,Guangcong Ruan,Liqin Fan,Yuting Tian,Zhifeng Xiao,Dongfeng Chen,Yanling Wei
Background: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut-brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. Methods: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut-brain axis. Results: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. Conclusions: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut-brain axis.
研究领域:
胃肠病学
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微生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 18
·期 4
·3691-3698
·
IF 1.922
Yan Zhou,Hanyang Liu,Jun Song,Liang Cao,Liming Tang,Chunjian Qi
Sinomenine (SIN), a pure alkaloid isolated from Sinomenium acutum, has been widely used in arthritis for its anti‑inflammatory effect, but little is known about the effect of SIN on human ulcerative colitis (UC). In the present study, the effect and mechanism of SIN was examined in a dextran sulfate sodium (DSS)‑induced murine colitis model, which mimics human UC. Oral administration of SIN significantly suppressed the elevated disease activity index and ameliorated colonic histological damage in a DSS‑induced colitis model. Tumor necrosis factor‑α, interleukin‑6 and inducible nitric oxide synthase levels were also reduced as detected by reverse transcription‑quantitative polymerase chain reaction. In addition, SIN reversed the decreased colon length and colonic superoxide dismutase activity. Furthermore, western blot analysis revealed that nuclear factor‑erythroid 2‑related factor 2 (Nrf2) and its downstream genes, heme oxygenase‑1 and NADP(H) quinone oxidoreductase 1 (NQO‑1), were markedly activated by SIN. The current results indicated that SIN alleviated DSS‑induced colitis in mice, which may be due to its antioxidant properties and was at least in part dependent on the Nrf2/NQO‑1 signaling pathway. Therefore, SIN may have potential applications as a protective drug for patients with UC.
研究领域:
药理学
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免疫学
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胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jiao Liu,Danye Niu,Yu Tang,Ruoheng Zheng,Yinyin Qin,Xiuqin Cheng,Shubo Pan,Jinfei Yuan,Xiaohua Shi,Jiao Yang
Background β-Hydroxy β-Methylbutyrate (HMB), derived from leucine, is known for its role in anti-oxidation and anti-inflammation. But, the application of HMB in IBD treatment is not fully understood, highlighting the requirement for further research. Purpose We aimed to examine the effects of HMB treatment on DSS-induced chronic colitis in mice and explore its underlying mechanisms. Methods To simulate colonic inflammation, a murine colitis model was generated by using DSS induction. Critical indicators such as body weight, colon length, disease activity index (DAI), and gross pathology were thoroughly monitored. Immunohistochemistry assay was conducted to assess the expression of Occludin and F4/80. Flow cytometry was employed to evaluate the expression levels of CD80 and CD86. qPCR was performed to measure cytokine expression (IL-6, IL-1β, TNF-α, IL-22, CXCL2, iNOS). RNA sequencing was carried out using bone-marrow derived dendritic macrophage cells (BMDMs). Results Our study indicates that HMB treatment substantially mitigated colonic damage in murine models of DSS-induced colitis, highlighting its anti-inflammatory potential. Notably, HMB significantly enhanced the expression of Occludin in these mice. Furthermore, HMB downregulated proinflammatory markers such as IL-6, IL-1β, and TNF-α as well as CXCL2 in the colon tissue. In vitro experiments also revealed that HMB reduced production of proinflammatory cytokines induced by DSS and suppressed the expression levels of CD80 and CD86 in macrophage cells. On a mechanistic level, we demonstrated the anti-inflammatory effects of HMB by reducing the phosphorylation of p-ERK and p-p65, thereby limiting cytokine production in both in vivo and in vitro settings. Conclusion These findings indicate that HMB possesses anti-inflammation against intestinal inflammation and may hold promise as a potential therapeutic candidate for IBD treatment. There's growing interest in combining traditional anti-inflammatory agents with supplements like HMB to improve outcomes in complex IBD cases. HMB's role in established muscle preservation and reduction of systemic inflammation as described in this study could make it a valuable adjunct in IBD therapy.
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
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