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
BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Xuchen Feng,Jun Ge,Hui Fu,Lin Miao,Feng Zhao,Jingyu Wang,Yujiao Sun,Yingpeng Li,Yunfei Li
Small molecules directly downregulating β-catenin could potentially offer a more effective therapeutic approach for combating against cancer stem cells, as compared to targeting the downstream components of the Wnt/β-catenin pathway. The challenge, however, lies in the fact that very few β-catenin suppressors have proven clinically effective, leaving a significant gap in medical solutions. Given that E-cadherin has a natural affinity for β-catenin, it stands to reason that agents designed to increase E-cadherin expression might provide an alternative method of regulating β-catenin levels. In this study, we report our discovery of DSS-C12 and DSS-B8, specific ester-based drugs derived from Dan-Shen-Su (DSS) extracted from the herb Salvia miltiorrhiza . Remarkably, these compounds display a potent ability to downregulate β-catenin, while also improving overall survival in post-surgery mice. Additionally, when these drugs are used in combination with PD-L1 checkpoint blockade, they stimulate enhanced systemic immune responses leading to significant suppression of primary tumor growth. In-depth mechanistic studies revealed that DSS-B8 functions as a vitamin D receptor agonist without inducing hypercalcemic effects. Collectively, our findings indicate that DSS-derived small molecules have considerable potential as clinically viable therapeutic strategies for β-catenin deactivation.
研究领域:
肿瘤学
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药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Yeye Hu,Yanting Wang,Haoyang Gao,Guigui Yang,Jing Xie,Ziliang He,Shenghui Lv,Fenglin Gu,Chaoqing Huang,Weicheng Hu
Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.
研究领域:
医学
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微生物学
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免疫学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2020
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IF 4.268
Dan Wang,Minghui Sun,Ying Zhang,Zehong Chen,Shuya Zang,Genyun Li,Gao Li,Andrew R. Clark,Jiangeng Huang,Luqin Si
Background Ulcerative colitis (UC) is an intricate enteric disease with a rising incidence that is closely related to mucosa-barrier destruction, gut dysbacteriosis, and immune disorders. Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, EMO) is a natural anthraquinone derivative that occurs in many Polygonaceae plants. Its multiple pharmacological effects, including antioxidant, immune-suppressive, and anti-bacteria activities, make it a promising treatment option for UC. However, its poor solubility, extensive absorption, and metabolism in the upper gastrointestinal tract may compromise its anti-colitis effects. Purpose EMO was loaded in a colon-targeted delivery system using multifunctional biomedical materials and the enhanced anti-colitis effect involving mucosa reconstruction was investigated in this study. Methods EMO-loaded Poly (DL-lactide-co-glycolide)/Eudragit Ⓡ S100/montmorillonite nanoparticles (EMO/PSM NPs) were prepared by a versatile single-step assembly approach. The colon-specific release behavior was characterized in vitro and in vivo , and the anti-colitis effect was evaluated in dextran sulfate sodium (DSS)-induced acute colitis in mice by weight loss, disease activity index (DAI) score, colon length, histological changes, and colitis biomarkers. The integrity of the intestinal mucosal barrier was evaluated through transwell co-culture model in vitro and serum zonulin-related tight junctions and mucin2 (MUC2) in vivo . Results EMO/PSM NPs with a desirable hydrodynamic diameter (~ 235 nm) and negative zeta potential (~ -31 mV) could prevent the premature drug release (< 4% in the first 6 h in vitro ) in the upper gastrointestinal tract (GIT) and boost retention in the lower GIT and inflamed colon mucosa in vivo . Compared to free EMO-treatment of different doses in UC mice, the NPs could enhance the remedial efficacy of EMO in DAI decline, histological remission, and regulation of colitis indicators, such as myeloperoxidase (MPO), nitric oxide (NO), and glutathione (GSH). The inflammatory factors including induced nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-1β were suppressed by EMO/PSM NPs at both mRNA and protein levels. The obtained NPs could also promote the regeneration of the mucosal barrier via reduced fluorescein isothiocyanate (FITC)-dextran leakage in the transwell co-culture model and decreased serum zonulin levels, which was demonstrated to be associated with the upregulated tight junctions (TJs)-related proteins (claudin-2, occludin, and zo-1) and MUC2 at mRNA level. Moreover, the NPs could contribute to attenuating the liver injury caused by free EMO under excessive immune inflammation. Conclusion Our results demonstrated that EMO/PSM NPs could specifically release EMO in the diseased colon, and effectively enhance the anti-colitis effects of EMO related to intestinal barrier improvement. It can be considered as a novel potential alternative for oral colon-targeted UC therapy by increasing therapeutic efficacy and reducing side-effects.
研究领域:
药学
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纳米技术
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胃肠病学
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免疫学
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材料科学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 7
·e70529
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IF 4.2
Hai-Xiang Guo,Zhong-Hao Ji,Bing-Bing Wang,Yu Xiao,Jin-Ping Hu,Yi Zheng,Wei Gao,Bao Yuan
Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in vitro. It was found that Lut treatment inhibited TM/TG-induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM-treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation-related diseases in humans. Graphical Luteolin modulates endoplasmic reticulum stress by targeting SIRT1 to ameliorate ulcerative colitis in mice.
研究领域:
药理学
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炎症性疾病
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分子生物学
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DOI
PubMed
高影响因子
Oncology Letters
·
2021
·Vol. 21
·期 3
·1-1
·
IF 2.967
Jiaxue Hao,Xufen Dai,Juan Gao,Yuexuan Li,Zhaoling Hou,Zhongman Chang,Yuxin Wang
Colorectal cancer (CRC) is the third most common cancer worldwide, with high incidence and mortality rates. Conventional therapies, including surgery, chemotherapy and radiation, are extensively used for the treatment of CRC. However, patients present with adverse effects, such as toxicity, hepatic injury and drug resistance. Thus, there is an urgent requirement to identify effective and safe therapy for CRC. Curcumin (CUR), a polyphenol substrate extracted from the rhizome of Curcuma longa, has been extensively studied for the treatment of CRC due to its high efficacy and fewer side effects. Previous studies have reported that several signaling pathways, such as NF‑κB, Wnt/β‑catenin, are involved in the antitumor effects of CUR in vitro. However, the effect and mechanisms in vivo are not yet fully understood. The present study aimed to determine the molecular mechanism of colorectal cancer in vivo. Reverse transcription‑quantitative PCR, western blot and immunohistochemistry analyses were performed to determine the underlying molecular mechanism of curcumin's anti‑cancer effect in azoxymethane‑dextran sodium sulfate induced colorectal cancer. The results of the present study demonstrated that CUR suppressed tumorigenesis in AOM‑DSS induced CRC in mice, and anticancer effects were exerted by suppressing the expression of pro‑inflammatory cytokines, and downregulating Axin2 in the Wnt/β‑catenin signaling pathway. Taken together, these results exhibit the potential in vivo mechanisms of the anticancer effects of CUR, and highlight Axin2 as a potential therapeutic target for CRC.
研究领域:
肿瘤学
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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
Signal Transduction and Targeted Therapy
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2023
·Vol. 8
·期 1
·1-17
·
IF 39.3
Liu Yi,Ji Yanhong,Jiang Ruiyi,Fang Chao,Shi Gang,Cheng Lin,Zuo Yinan,Ye Yixin,Su Xiaolan,Li Junshu,Wang Huiling,Wang Yuan,Lin Yi,Dai Lei,Zhang Shuang,Deng Hongxin
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.
研究领域:
胃肠病学
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肿瘤学
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老年医学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2025
·
IF 4
Lifang Feng,Tianyu Zhang,Wei Ye,Daofeng Qu
Resveratrol and rutin, two polyphenolic compounds, can effectively alleviate the symptoms of ulcerative colitis (UC), leading to conflicts in recommending resveratrol- or rutin-rich diets to UC patients, who do not know which type of diet is more effective in alleviating UC symptoms. In this study, administration of resveratrol or rutin alleviated DSS-induced UC mice, including reduction of DAI, serum levels of inflammatory cytokines and oxidant, and improvement of colonic health status. Differentially expressed genes resulting from resveratrol and rutin treatment in DSS-induced UC mice at the genome-wide level from scratch and elucidated the mechanism by which they affected the polarization of intestinal epithelial T cells by promoting Treg cells and inhibiting Th17 cells to alleviate UC symptoms, and rutin was greater than resveratrol. In addition, rutin-rich foods were superior to resveratrol-rich foods in ameliorating UC symptoms in mice. Our findings suggest that UC patients consume rutin-rich foods to better alleviate intestinal inflammation.
研究领域:
免疫学
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胃肠病学
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营养生物化学
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分子生物学
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产品关联
DOI
高影响因子
Journal of Functional Foods
·
2026
·
IF 3.9
Zixuan Cui,Xiaojing Chen,Yufeng Wei,Danfei Huang,Chang Li
Jujube polysaccharides and nano‑selenium have gained attention for their bioactivity. This study used jujube polysaccharides to stabilize selenium nanoparticles (JP-SeNPs) via redox method. The optimized JP-SeNPs had an average size of 142.0 nm (PDI 0.1989), contained zero-valent selenium, showing no HepG2 toxicity at 5–40 μg/mL. In DSS-induced colitis mice, JP-SeNPs alleviated weight loss, disease activity, and colon shortening, reduced histopathological damage, restored goblet cells and tight junctions, and lowered colonic TNF-α, IL-1β, IFN-γ, and serum endotoxin. Cecal short-chain fatty acids (acetate, propionate, butyrate) rebounded. 16S rRNA sequencing revealed enhanced α-diversity, enrichment of butyrate-producers, and restored carbohydrate metabolism. JP-SeNPs ameliorate colitis via barrier repair, inflammation suppression, microbiota modulation, and SCFA promotion, supporting its development as a functional formulation.
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产品关联
DOI
高影响因子
Foods
·
2026
·Vol. 15
·期 7
·1131
·
IF 6
Jiyu Nie,Danying Chen,Chengfeng Yu,Zengliang Jiang,Haibo Pan,Xingqian Ye,Shiguo Chen
Carrageenan (CGN) is widely used in processed foods and is typically supplied as a commercial preparation blended with other hydrocolloids to improve gelling properties, rather than as a single purified polymer. However, safety evaluations and mechanistic studies have largely focused on CGN in isolation; as a result, the biological effects of commercial CGN preparations (CGNPs) under realistic exposure conditions are still insufficiently characterized. In this study, the structural characteristics of three commercial food-grade CGNPs intended for meat products, soft sweets, and jelly were investigated. Furthermore, their effects on colitis were assessed, along with their impacts on the gut microbiota and related metabolites. The results indicated that all three CGNPs were κ-type, but differed in monosaccharide composition and molecular weight, which may contribute to their biological differences. In vivo, the CGNP intended for soft sweets significantly reduced the disease activity index (n= 6/group,p< 0.05) and helped maintain colon length (n= 6/group,p< 0.05). This CGNP also markedly reduced the abundance ofEscherichia-ShigellaandHelicobacter, while increasing propionate levels (n= 6/group,p< 0.05). In contrast, CGNPs intended for meat products and jelly tended to exacerbate colitis and increased the abundance ofEnterococcus, a genus associated with colitis. These findings reveal the application-specific biological effects of commercial food-grade CGNPs and provide a basis for optimizing the application of these preparations in the food industry.
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DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE
·
2026
·
IF 3.4
Wu Wei-tong,Huang Jia-yi,Lai Yi-shan,Tan Hui-lan,Wang Lang-hong,Zeng Xin-An,Huang Yan-yan
Colitis is an intestinal disorder characterized by colonic mucosal or submucosal inflammation. Probiotic intervention is a potential biotherapeutic strategy for adjuvant colitis management. This study evaluated the effects of Lactiplantibacillus plantarum HYY-DB36 ( L. plantarum DB36) using a dextran sulfate sodium (DSS)-induced murine colitis model. Key findings: compared with the DSS model group, L. plantarum DB36 significantly ameliorated colonic histopathological damage and inflammation, elevated intestinal short-chain fatty acid levels, suppressed harmful bacteria proliferation, and promoted beneficial bacteria enrichment. In conclusion, L. plantarum DB36 has great potential for adjuvant colitis therapy, with its role in modulating intestinal microbial homeostasis supporting its promise as a probiotic resource for alleviating colitis symptoms. Graphical abstract The Potential Specific Mechanism by Which L.plantarum DB36 Alleviates DSS-Induced Colitis Through Modulation of the Gut Microbiota.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Rui Li,Jiaojiao Mou,Lei Zhao,Mengqiu Hu,Bin Wang,Yanying Sun,Jing Liu,Xiaohui Qi,Jie Yang
Intestinal barrier disruption and oxidative stress are the major pathological features during the ulcerative colitis (UC). The present research aimed to explore the amelioration property of fucoidan of Stichopus chloronotus (Fuc Sc) against dextran sulfate sodium (DSS) resulted UC. The findings from our study suggest that treating with Fuc-Sc improved the integrity of the Caco-2 monolayer through raising its TEER value, reducing LDH release, promoting the tight junction proteins (TJs) in Caco-2 cells, and shielding the cells from decreases of these proteins caused by H 2 O 2 . Besides, Fuc-Sc activated Nrf2/HO-1 pathway to facilitate the antioxidant activities of Caco-2 cells under oxidative stress through elevating the SOD and GSH, and reducing LDH and MDA. Furthermore, oral administration of Fuc-Sc attenuated DSS resulted body weights decrease, DAI score increase, colon length decrease, and structural damage of colon tissue. Fuc-Sc also promoted the barrier function and suppressed oxidative injury via activation of Nrf2/HO-1 signal pathway. Collectively, this research provided the theoretical foundation for fucoidan as a promising functional food for colitis.
研究领域:
营养学
·
消化病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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