BIOMEDICINE & PHARMACOTHERAPY
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2022
·
IF 7.419
Jingyi Hu,Yiheng Tong,Zhaofeng Shen,Yanan Li,Cheng Cheng,Ryan Au,Feng Xu,Yajun Liu,Lei Zhu,Hong Shen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae , maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun , is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli ( E. coli, family of Enterobacteriaceae ) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae . Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.
研究领域:
药理学
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微生物学
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免疫学
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胃肠病学
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PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
·
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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PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 06
·1527-1546
·
IF 5.7
Cheng-Xi Li,Yu-Meng Wang,Wen-Jing Zhang,Shu Zhang,Jian-Ping Li,Tong Zhou,Jin-Ao Duan,Jian-Ming Guo
Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10 − ∕ − ). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF- α levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10 − ∕ − mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae , Sutterellaceae , Erysipelotrichaceae , Burkholderiaceae , Desulfovibrionaceae , and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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Antioxidants
·
2025
·Vol. 14
·期 10
·1256
·
IF 6.6
Jinfeng Guo,Yilin Sun,Kaiqi Gao,Haijie Zhao,Yue Su,Ying Zhao,Yu Zhang,Yujun Jiang
Ulcerative colitis (UC) with multifactorial etiology remains clinically challenging. While current pharmacotherapies alleviate symptoms, their long-term application is constrained by significant side effects.Lacticaseibacillus paracaseiJY062 postbiotic (Pa JY062) exerts multi-target therapeutic effects via integrated antioxidant, barrier repair, immunomodulatory and microbiota modulation for UC. Pa JY062 exhibited potent antioxidant capacity and reduced reactive oxygen species (ROS) in Caco-2 cells. In DSS-colitis mice, high-dose Pa JY062 (HP, 800 mg/kg) restored intestinal barrier integrity (Evans blue permeability: 0.0547 vs. 0.107,p< 0.01), enhanced antioxidant defenses (SOD: 9.43 vs. 5.5; GSH-Px: 62.74 vs. 40.94 U/mg protein,p< 0.01), and rebalanced Th1/Th2/Th17/Treg responses.LigiLactobacillus murinus(L. murinus) was enriched, whileBacteroides acidifaciens(B. acidifaciens) was diminished, SCFAs increased (acetate 2772.70 ± 21.08, propionate 669.84 ± 6.79, butyrate 324.14 ± 0.42 μg/g). Spearman correlations linkedL. murinusto barrier proteins (ZO-1/Occludin/E-cadherin), contrastingB. acidifaciens–inflammation associations. These findings revealed that Pa JY062 exerted multi-target therapeutic effects on UC, and offered a wider array of options for intestinal health. Pa JY062 represents a promising natural antioxidant-based strategy for UC management.
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CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 3
·e03104
·
IF 2.9
Yingjian Lu,Le Li,Zhuolun Xin,Xiangfei Li
UC is a globally escalating intestinal disorder with limited safe and effective interventions. This study investigated the synergistic therapeutic effects and mechanisms of Lactobacillus johnsonii 46 ( L. johnsonii 46) (a feruloyl esterase-producing strain) and rice bran (LJRB) on DSS-induced UC in C57BL/6J mice. The animal groups were divided into control group (CON), DSS group (MOD), sulfasalazine group (SUL), rice bran group (RBN), L. johnsonii 46 group (LAJ), and LJRB treatment group (RBL). The organ index, disease index, and biochemical indicators of mice were measured, the histopathology of the colon was analyzed. The expression of inflammatory factor, tight junction protein and TLRs/TRAF6/NF-κB signaling pathway genes were detected by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). LJRB supplementation exerted superior protective effects compared to single rice bran (RBN) or L. johnsonii 46 (LAJ) intervention: it significantly alleviated DSS-induced weight loss (RBL group: 1.46 ± 0.21 g vs. MOD group: ∼3 g, p < 0.05), restored colon length, and reduced the disease activity index (DAI) by ∼50%. Biochemical and molecular analyses showed LJRB remarkably suppressed serum pro-inflammatory cytokines (IL-1β, TNF-α, IL-6; 40%–60% reduction vs. MOD group) while elevating anti-inflammatory IL-10 (∼35% increase), enhanced colonic antioxidant capacity (reduced MDA by ∼30% and increased SOD, GSH, GSH-Px by 25%–40%), and enriched cecal short-chain fatty acids (SCFAs) with acetic acid (0.99 µmol/g), propionic acid (0.31 µmol/g), and butyric acid (0.21 µmol/g) significantly higher than the MOD group. Mechanistically, LJRB synergistically inhibited the TLRs/TRAF6/NF-κB signaling pathway, as indicated by downregulated mRNA expression of TLR4, MyD88, IKKβ, and NF-κB p65 (30%–50% reduction vs. MOD group) and decreased phosphorylation of IKKβ, IκBα, and NF-κB p65 proteins. Histopathological observations confirmed LJRB preserved colon tissue integrity, reduced goblet cell loss, and alleviated mucosal erosion and edema. Collectively, these findings demonstrate LJRB alleviates UC through multi-targeted mechanisms (anti-inflammation, antioxidation, SCFA production promotion, and nuclear factor kappa-B (NF-κB) pathway inhibition), highlighting its potential as a novel natural dietary supplement for UC prevention and management. Graphical Synergistic protective effects of rice bran combined with Lactobacillus johnsonii 46 on DSS-induced ulcerative colitis in mice: Evaluated by clinical, biochemical, histopathological and molecular biological assays.
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Journal of Materials Chemistry B
·
2026
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IF 6.2
Jiahao Du,Yunyun Sun,Dong Yu,Shengwei Lu,Simin Yu,Mei Wang,Guoqing Zhou,Songxin Xu,Lei Zhang,Yefei Zhu,Longxiang Zhou
Inflammatory bowel disease (IBD) is a refractory gastrointestinal disorder characterized by sustained intestinal inflammation, mucosal barrier dysfunction, and gut dysbiosis. Excess reactive oxygen species (ROS) is a key driver of these pathological processes. Although CeO₂-based nanozymes can scavenge ROS, its clinical application is limited by poor aqueous stability. Here, we developed an oral nanozyme by co-encapsulating ultrasmall CeO₂ nanoparticles and the clinical drug 5-aminosalicylic acid (5-ASA) within liposomes. The resulting formulation (CeLA) exhibited excellent colloidal stability and robust ROS-scavenging activity, and provided marked cytoprotection against oxidative stress in vitro. In a dextran sulfate sodium (DSS)-induced colitis model, CeLA alleviated clinical symptoms, restored intestinal barrier integrity, and suppressed pro-inflammatory cytokine expression. Notably, CeLA also reshaped the dysbiotic gut microbiome by reducing pro-inflammatory bacterial taxa. This multifunctional nanozyme integrates antioxidant, anti-inflammatory, and microbiome-modulating effects, offering a promising therapeutic strategy for IBD.
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Food & Function
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2025
·
IF 5.4
Le Wang,Houzhen Lu,Haitao Gui,Zifu Ni,Zhongke Sun,Zihua Wang,Zhihua Wang,Xuanyan Liu,Qipeng Yuan
Ulcerative colitis (UC) is a prevalent inflammatory bowel disease (IBD) posing a significant health threat. This study explored the protective effects of D-tagatose against DSS-induced colitis in mice and its underlying mechanisms using H&E staining, AB-PAS staining, immunofluorescence, immunohistochemistry, ELISA, qPCR, western blotting, and other assays. D-Tagatose improved colitis by increasing body weight and colon length, with decreased DAI (disease activity index) and histopathological scores. The results showed that D-tagatose inhibited the secretion of myeloperoxidase (MPO), inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) as well as increased the content of anti-inflammatory cytokines (IL-10) in vitro. In addition, D-tagatose enhanced the expression of tight junction proteins (ZO-1 and Occludin) and mucin (MUC-2). Furthermore, D-tagatose was able to modulate the gut microbiota dysbiosis caused by DSS-induced UC and increased the content of short-chain fatty acids (SCFAs). This study indicated that D-tagatose attenuated DSS-induced UC by modulating inflammatory cytokines, restoring intestinal barrier function, maintaining gut microbiota homeostasis, and enhancing SCFA production. These findings provide D-tagatose as a safe and effective novel functional food strategy for the prevention and treatment of UC.
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INFLAMMOPHARMACOLOGY
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2025
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IF 5.3
Xiang Meixian,Wu Songtao,Liu Minxin,Zhang Bin,Xia Xiankun,Tan Wenjing,Xiang Shijian
Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus , Bifidobacterium , and Akkermansia . They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1 , BDKRB1 , LCN2 , and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses. Graphical abstract
研究领域:
医学
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微生物学
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分子生物学
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高影响因子
Nutrients
·
2025
·Vol. 17
·期 18
·2988
·
IF 5
Hedong Jiang,Gonglong Li,Liuming Xie,Nanhai Zhang,Yi Huang,Xinli Liang,Fanghua Guo,Qieying Jiang,Zhenggen Liao
Background: Curcumin (Cur) and tryptophan (Trp) both show promise for treating ulcerative colitis (UC) alone, but their combination has not been explored. This study investigated the therapeutic advantage of the combination (Cur–Trp) for DSS-induced ulcerative colitis in mice.Methods: We established a mouse model of ulcerative colitis induced by dextran sulfate sodium (DSS). The mice were treated with Cur, Trp, or Cur–Trp, and to evaluate the therapeutic effects, we assessed clinical signs such as body weight, disease activity index (DAI), and colon length. We also examined intestinal barrier function through indicators including histopathological changes, inflammatory factors, oxidative stress levels, mucin secretion, and tight junction protein expression. Additionally, we analyzed the composition of gut microbiota and the content of its metabolites like short-chain fatty acids (SCFAs).Results: The Cur–Trp group produced the most significant improvement, exceeding that of Cur or Trp group. This was evidenced by a significant recovery of this sign, including slower weight loss, reduced colon shortening, and de-creased disease activity index. Compared with the model group, the weight loss of mice in the Cur–Trp group was reduced from 17.15% to 9.73%, which was better than that in the cur group (11.33%) and the Trp group (11.59%). The DAI decreased from the model group (3.6) to the Cur–Trp group (2.4), while the DAI in the Cur group and the Trp group only decreased to 2.9 and 2.8, respectively. The colon length in the Cur–Trp group (6.52 cm) was larger than that in the cur group (6.31 cm), the Trp group (6.23 cm) and the model group (5.5 cm). The Cur–Trp intervention effectively restored intestinal barrier function, as shown by reducing colon tissue dam-age, modulating inflammatory factors, restoring oxidative balance, increasing mucin secretion, and upregulating tight junction protein expression. Further studies showed that the combination uniquely modulated the gut microbiome, increased the Firmicutes/Bacteroidetes (F/B) ratio, decreased the genus of pro-inflammatory bacteria, and in-creased beneficial bacteria, while increasing SCFA levels to alleviate DSS-induced ulcerative colitis.Conclusions: Cur–Trp has shown great potential in alleviating colitis and promoting intestinal barrier function, suggesting that the combination of Cur and Trp has the potential to be developed as a therapeutic functional food or dietary supplement for UC. However, more studies are needed to validate this finding. Future research should focus on elucidating the precise molecular mechanisms, optimizing dosage and clinical trials in chronic models and humans to provide more targeted treatment options.
研究领域:
药理学
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胃肠病学
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营养科学
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微生物组研究
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PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 11
·2765
·
IF 4.35
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
As a processing by-product, green pea hull (GPH) was found to be rich in phenolic components in our previous studies. In this study, UHPLC-LTQ-OrbiTrap-MS (Ultra performance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry) technique was used to quantify polyphenols, and DSS (sodium dextran sulfate)-induced colitis mouse model was established to explore the effect of GPH extracts on colitis. The results showed that quercetin and its derivatives, kaempferol trihexanside and catechin and its derivatives were the main phenolic substances in the extract, reaching 2836.57, 1482.00 and 1339.91 µg quercetin/g GPH extract, respectively; GPH extracts can improved inflammatory status, repaired colonic function, regulated inflammatory factors, and restored oxidative balance in mice. Further, GPH extracts can activate Keap1-Nrf2-ARE signaling pathway, regulate downstream antioxidant protease and gut microbiota by increasing F/B value and promoting the growth ofLactobacillaceaeandLachnospiraceae, and improve the level of SCFAs (short-chain fatty acids) to relieve DSS-induced colitis in mice. Therefore, GPH may be a promising dietary resource for the treatment of ulcerative colitis.Keywords:polyphenols;colitis;UHPLC-LTQ-OrbiTrap-MS;GPH extracts;Keap1-Nrf2;gut microbiota
研究领域:
药理学
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营养学
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免疫学
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微生物学
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PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2023
·
IF 4.6
Da Huang,Minglang Zou,Chenlan Xu,Yongming Wang,Zhenjin Xu,Wancong Zhang,Shijie Tang,Zuquan Weng
Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch–curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium, yielding multiple drug-loaded microcapsules (Crohn's-disease/DA-loaded HES─CUR microcapsules, CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran-sulfate-sodium-induced UC mouse model reveal that CDHC-MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.
研究领域:
药剂学
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炎症性疾病研究
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生物材料科学
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高影响因子
Antioxidants
·
2023
·Vol. 12
·期 7
·1400
·
IF 7
Ke Ning,Yameng Duan,Weiwei Tong,Yue Chen,Qinghui Zhang,Qiuhong Xie,Hongyu Xiang
Purslane, a common wild vegetable, contains active substances with various biological functions. However, its effects have been under-investigated in ulcerative colitis (UC). Therefore, this study investigated the therapeutic effects of purslane macromolecular (POEM) and small molecular extracts (POES) on dextran sulfate sodium (DSS)-induced UC in mice. Membrane separation was used to obtain extracts of different molecular weights, and their compositional differences were compared using liquid chromatography–mass spectrometry (LC/MS). POEM contained more proteins and polysaccharides, whereas POES contained more organic acids and alkaloids. These differences in composition were directly responsible for the different degrees of remission of the alleviated UC in model mice. POEM may alleviate UC by regulating the antioxidant capacity and the gut microbiota, whereas the major alleviatory effect of POES was primarily related to the regulation of antioxidant capacity. The POEM and POES effects identified in this study provide a theoretical basis for the development of purslane as a functional food.Keywords:ulcerative colitis;macromolecular extract;purslane;oxidative stress;small molecular extract;gut microbiota;Portulaca oleraceaL.
研究领域:
药理学
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胃肠病学
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营养学
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生物化学
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高影响因子
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