دورية أكاديمية
Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans.
| العنوان: | Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans. |
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| المؤلفون: | Wu Z; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Zhang J; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350108, China., Wu Y; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Chen M; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Hu H; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350108, China., Gao X; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Li C; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Li M; Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, 518132, China., Zhang Y; State key laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China., Lin X; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China., Yang Q; Department of Gynecology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital, Fuzhou, 350001, China., Chen L; Department of Gynecology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital, Fuzhou, 350001, China., Chen K; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China. Electronic address: kunqi.chen@fjmu.edu.cn., Zheng L; Department of Orthopedics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China. Electronic address: zlf0362@163.com., Zhu A; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China. Electronic address: zhuan@fjmu.edu.cn. |
| المصدر: | Chemico-biological interactions [Chem Biol Interact] 2024 May 25; Vol. 395, pp. 111036. Date of Electronic Publication: 2024 May 04. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| مواضيع طبية MeSH: | Caenorhabditis elegans*/drug effects , Caenorhabditis elegans*/metabolism , Reactive Oxygen Species*/metabolism, Animals ; Quinoxalines/pharmacology ; Caenorhabditis elegans Proteins/metabolism ; Caenorhabditis elegans Proteins/genetics ; Oxidative Stress/drug effects ; Intestines/drug effects ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/drug effects ; Gelsemium/chemistry ; Unfolded Protein Response/drug effects ; Permeability/drug effects ; Lipofuscin/metabolism ; Locomotion/drug effects ; Indole Alkaloids |
| مستخلص: | Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPR ER ) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPR ER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Caenorhabditis elegans; Gelsenicine; Intestinal toxicity; Oxidative stress; Permeability |
| المشرفين على المادة: | 0 (gelsenicine) |
| تواريخ الأحداث: | Date Created: 20240505 Date Completed: 20240519 Latest Revision: 20240519 |
| رمز التحديث: | 20240520 |
| DOI: | 10.1016/j.cbi.2024.111036 |
| PMID: | 38705443 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7786 |
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| DOI: | 10.1016/j.cbi.2024.111036 |