Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans

作者：Zekai Wu, Jian Zhang, Yajiao Wu, Mengting Chen, Hong Hu, Xinyue Gao, Chutao Li, Maodong Li, You-Bo Zhang, Xiaohuang Lin, Qiaomei Yang, Li Chen, Kunqi Chen, Lifeng Zheng, An Zhu · 发表于：Chemico-Biological Interactions · 年份：2024 · DOI：10.1016/j.cbi.2024.111036 · 被引用次数：15 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Selenium in Biological Systems、Coenzyme Q10 studies and effects

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 (UPRER) 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 intes...