Frontiers in Pharmacology
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2024
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IF 4.4
Shu Long,Fu Hangjie,Pi Aiwen,Feng Yuliang,Dong Hui,Si Caijuan,Li Songtao,Zhu Feiye,Zheng Peifen,Zhu Qin
Ulcerative colitis (UC) is a recurring inflammatory bowel disease, in which oxidative stress plays a role in its progression, and regulation of the oxidative/antioxidative balance has been suggested as a potential target for the treatment of UC. The aim of this study was to evaluate the protective effect of andrographolide against UC and its potential antioxidant properties by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Dextran sulfate sodium (DSS) -induced UC mice and the LPS-induced HT29 inflammatory cell model were established to uncover the potential mechanisms of andrographolide. ML385, a Nrf2 inhibitor, was used in both models to assess whether andrographolide exerts a protective effect against UC through the Nrf2/HO-1 pathway. The in vivo experiment showed that andrographolide ameliorated the symptoms and histopathology of DSS-induced mice and restored the expressions of ZO-1, Occludin-1 and Claudin-1. Meanwhile, DSS-induced oxidative stress and inflammation were suppressed by andrographolide treatment, along with the upregulation of key proteins in the Nrf2/HO-1 pathway. In vitro experiments showed that andrographolide attenuated LPS-induced excessive generation of ROS in HT29 cells, reduced inflammatory factors, and upregulated the expression of proteins related to tight junctions and Nrf2/HO-1 pathway. In addition, ML385 abolished the beneficial effect of andrographolide. In conclusion, the protective effect of andrographolide against UC may involve the suppression of oxidative stress and inflammation via the Nrf2/HO-1 pathway.
研究领域:
药理学
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炎症性肠病
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2021
·Vol. 11
·期 1
·1-13
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IF 4.38
Su Le,Su Yue,An Zaiyong,Zhang Ping,Yue Qiulin,Zhao Chen,Sun Xin,Zhang Song,Liu Xinli,Li Kunlun,Zhao Lin
With the increased incidence and recognition, ulcerative colitis (UC) has become a global public health problem in the world. Although many immunosuppressant and biological drugs have been used for UC treatment, the cure rate is still very low. It is necessary to find some safe and long-term used medicine for UC cure. Recently, the Chinese traditional herb Danshen has been investigated in the treatment of UC. However, it is a limitation of Danshen that many of the active components in Danshen are not easily absorbed by the human body. Probiotics could convert macromolecules into smaller molecules to facilitate absorption. Thus, Lactobacillus rhamnosus (F-B4-1) and Bacillus subtillis Natto (F-A7-1) were screened to ferment Danshen in this study. The fermented Danshen products were gavaged in the dextran sulfate sodium (DSS)-induced UC model mice. Danshen had better results to attenuate symptoms of DSS-induced UC after fermented with F-B4-1 and F-A7-1. Loss of body weight and disease activity index (DAI) were reduced. The abnormally short colon lengths and colonic damage were recovered. And fermented Danshen had the better inhibitory effect than Danshen itself on pro-inflammatory cytokine expression during DSS-induced UC. The results indicated that compared with Danshen, fermented Danshen relieved DSS-induced UC in mice more effectively. Danshen fermented by probiotics might be an effective treatment to UC in clinic stage in the future.
研究领域:
胃肠病学
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药理学
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中药学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Shumeng Hu,Runan Zhao,Tao Chen,Xuesong Chi,Yangjing Li,Di Wu,Bei-Wei Zhu,Jiangning Hu
The onset and progression of ulcerative colitis (UC) are intricately linked to the worsening of intestinal inflammation, an imbalance in oxidative stress, and impairment of the intestinal mucosal barrier. Although chlorogenic acid (CA) shows potential in effectively alleviating symptoms of UC, its clinical application is hindered by poor bioavailability, stability, rapid metabolism, and quick excretion. This study utilized a one-step enzyme-catalyzed polymerization technique to create chlorogenic acid nanoparticles (CA NPs), aiming to improve the bioavailability and stability of CA. The CA NPs exhibited an optimal nano size (106.65 ± 4.12 nm) and showed increased cellular uptake over time. Importantly, CA NPs significantly prolonged retention time in inflamed colonic tissues, enhancing accumulation and providing a targeted therapy for UC. Animal studies confirmed the substantial benefits of CA NPs, including reduced weight loss, lessened reduction in colon length, and a lowered disease activity index (DAI) score in DSS-induced UC mice. Moreover, CA NPs effectively reduced oxidative stress and levels of inflammatory factors in the colonic tissues of UC mice, thus mitigating tissue damage and restoring the integrity of the intestinal mucosal barrier. In conclusion, our research proposes a novel approach to increase the bioavailability and stability of CA, offering a promising avenue for its effective application in preventing UC.
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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药理学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2024
·Vol. 29
·期 5
·1-14
·
IF 3.4
Xinya Yu,Xiaoxi Li,Yunchun Xu,Yuwei Li,Ye Zhou,Junhua Zhang,Le Guo
Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL‑6, IL‑1β, TNF‑α and IL‑10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)‑1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti‑inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.
研究领域:
药理学
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炎症性肠病
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分子生物学
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动物模型
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Congcong Li,Lu Wang,Juebo Zhao,Yucai Wei,Shuo Zhai,Min Tan,Kuikui Guan,Zhihong Huang,Chaoxi Chen
Background Lonicera rupicola Hook.f.et Thoms (LRH) is used as a customary medicinal herb in Tibetans. And LRH flavonoids have excellent anti-inflammatory and antioxidant pharmacological activities. However, the specific effects of LRH and its mechanism remain unknown, and there is a deficiency of systematic research, leading to the waste of LRH as a medicinal resource. Purpose In this study, in an attempt to rationalize the development and utilization of Tibetan herbal resources, the therapeutic efficacy and the underlying molecular mechanisms of LRH flavonoids on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were investigated, establishing the favorable basis for the pharmacodynamic material basis of LRH and providing a scientific basis for the discovery of new drugs for the treatment of UC. Methods Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for identification and detection of the flavonoid components of LRH. Meanwhile, their potential targets, biological functions and signaling pathways were predicted with the assistance of network pharmacology analysis. Subsequently, pharmacological efficacy of LRH were evaluated by body weight loss, colon length, disease activity index (DAI), histology observation and the expression levels of inflammatory mediators, messenger RNA (mRNA) and tight junction proteins. Moreover, in the present investigation, we also profiled the gut microbiome via high-throughput sequencing of the V3 - V4 region of 16S ribosomal DNA (rDNA) for bacterial community composition and diversity by Illumina MiSeq platforms. Finally, the key regulatory proteins in the PI3K/AKT pathways were measured to investigate their underlying molecular mechanisms. Results A total of 37 LRH flavonoid components were identified and detected by UPLC-MS/MS, and 12 potential active components were obtained after screening. 137 of their common targets with UC were further predicted . GO and KEGG pathway enrichment analysis and molecular docking experiments demonstrated that LRH flavonoids could interfere with UC through "multi-component-multi-target-multi-pathway". In the animal experiments, LRH flavonoids could significantly attenuate UC as demonstrated by reducing the body weight loss and DAI, restoring colon length, decreasing oxidative stress, and improving the intestinal epithelial cell barrier. The mRNA and proteins expression levels of inflammatory mediators were returned to dynamic balance following LRH flavonoids treatment. 16S rDNA sequence analysis indicated that LRH flavonoids promoted the recovery of gut microbiome. And the PI3K/AKT pathway was significantly suppressed by LRH flavonoids. Conclusions LRH flavonoids exhibited multifaceted protective effects against DSS-induced UC in mice through mitigating colon inflammation and oxidative stress, restoring epithelial barrier function, and improving the gut microenvironment potentially through modulation of the PI3K/AKT pathway. This finding demonstrated that LRH flavonoids possessed great potential for becoming an excellent drug for the treatment of UC.
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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分子生物学
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Wei Niu,Yuelin Dong,Ziwei Fu,Jiajie Lv,Ligui Wang,Zhenhai Zhang,Jiege Huo,Jianming Ju
This study investigated the therapeutic effects and mechanisms of chitosans (CSs) with different molecular weights on ulcerative colitis (UC). Three size classes of CSs (Mw ≤ 3, 50, and 200 kDa) were used in this study. The effect of large CSs (Mw ≤ 200 kDa) on UC was the best, followed by that of medium CSs (Mw ≤ 50 kDa), and that of small CSs (Mw ≤ 3 kDa) was the least in the LPS-induced Raw 264.7 cell model and DSS-induced UC mice model. The therapeutic mechanisms of three CSs are related to anti-oxidation, anti-inflammation, and regulation of immunoglobulin and intestinal flora by attenuating body weight loss, decreasing the disease activity index (DAI) and MPO activity, suppressing proinflammatory cytokines and IgG levels, down-regulating the level of oxidative stress, increasing anti-inflammatory cytokines, SOD activity and Prevotellaceae_UCG-001 levels, and reducing the abundance of Proteobacteria, Actinobacteria, and Escherichia-Shigella . In general, the molecular weight of CSs influences their efficacy against UC. CSs with an optimal molecular weight demonstrate good development prospects for ameliorating UC.
研究领域:
药理学
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免疫学
·
微生物学
·
炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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