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Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia
There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100595/ https://www.ncbi.nlm.nih.gov/pubmed/33967762 http://dx.doi.org/10.3389/fphar.2021.629125 |
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author | Yan, Tao Guo, Shun Zhang, Tian Zhang, Zhimin Liu, An Zhang, Song Xu, Yuan Qi, Yuhong Zhao, Weihe Wang, Qinhui Shi, Lei Liu, Linna |
author_facet | Yan, Tao Guo, Shun Zhang, Tian Zhang, Zhimin Liu, An Zhang, Song Xu, Yuan Qi, Yuhong Zhao, Weihe Wang, Qinhui Shi, Lei Liu, Linna |
author_sort | Yan, Tao |
collection | PubMed |
description | There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays an important role in the occurrence of enteritis. Previous studies have shown that targeting GTP-cyclohydrolase 1 (Gch1) to improve intestinal ischemia could be a new strategy to prevent and treat RE. A high content of the naturally occurring phthalide derivative ligustilide (LIG) has been found in the plant drug Rhizoma Ligustici Chuanxiong for the treatment of cardiovascular diseases. The purpose of this study was to evaluate the protective effects of LIG on RE. Ionizing radiation (IR) rat and endothelial cell models were used to observe and record rat body weights and stool morphologies, measure intestinal blood perfusion by laser Doppler blood flow imaging, determine the diastolic functions of mesenteric arteries, detect the levels of Gch1/BH(4)/eNOS pathway-related proteins and regulatory molecules in the mesenteric arteries and endothelial cells, and predict affinity by molecular docking technology. The results showed that LIG significantly improved the body weights, loose stools, intestinal villi lengths, intestinal perfusion and vasodilatory functions of IR rats. LIG also significantly improved Gch1 protein and BH(4) levels in the mesenteric arteries and endothelial cells after IR, increased the NO content, reduced superoxide accumulation, and improved p-eNOS (Ser1177) levels in endothelial cells. LIG has good affinity for Gch1, which significantly improves its activity. These results indicate that LIG is the preferred compound for the prevention and treatment of RE by improving intestinal ischemia through the Gch1/BH(4)/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE. |
format | Online Article Text |
id | pubmed-8100595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81005952021-05-07 Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia Yan, Tao Guo, Shun Zhang, Tian Zhang, Zhimin Liu, An Zhang, Song Xu, Yuan Qi, Yuhong Zhao, Weihe Wang, Qinhui Shi, Lei Liu, Linna Front Pharmacol Pharmacology There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays an important role in the occurrence of enteritis. Previous studies have shown that targeting GTP-cyclohydrolase 1 (Gch1) to improve intestinal ischemia could be a new strategy to prevent and treat RE. A high content of the naturally occurring phthalide derivative ligustilide (LIG) has been found in the plant drug Rhizoma Ligustici Chuanxiong for the treatment of cardiovascular diseases. The purpose of this study was to evaluate the protective effects of LIG on RE. Ionizing radiation (IR) rat and endothelial cell models were used to observe and record rat body weights and stool morphologies, measure intestinal blood perfusion by laser Doppler blood flow imaging, determine the diastolic functions of mesenteric arteries, detect the levels of Gch1/BH(4)/eNOS pathway-related proteins and regulatory molecules in the mesenteric arteries and endothelial cells, and predict affinity by molecular docking technology. The results showed that LIG significantly improved the body weights, loose stools, intestinal villi lengths, intestinal perfusion and vasodilatory functions of IR rats. LIG also significantly improved Gch1 protein and BH(4) levels in the mesenteric arteries and endothelial cells after IR, increased the NO content, reduced superoxide accumulation, and improved p-eNOS (Ser1177) levels in endothelial cells. LIG has good affinity for Gch1, which significantly improves its activity. These results indicate that LIG is the preferred compound for the prevention and treatment of RE by improving intestinal ischemia through the Gch1/BH(4)/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE. Frontiers Media S.A. 2021-04-22 /pmc/articles/PMC8100595/ /pubmed/33967762 http://dx.doi.org/10.3389/fphar.2021.629125 Text en Copyright © 2021 Yan, Guo, Zhang, Zhang, Liu, Zhang, Xu, Qi, Zhao, Wang, Shi and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Yan, Tao Guo, Shun Zhang, Tian Zhang, Zhimin Liu, An Zhang, Song Xu, Yuan Qi, Yuhong Zhao, Weihe Wang, Qinhui Shi, Lei Liu, Linna Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title | Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title_full | Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title_fullStr | Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title_full_unstemmed | Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title_short | Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH(4)/eNOS to Improve Intestinal Ischemia |
title_sort | ligustilide prevents radiation enteritis by targeting gch1/bh(4)/enos to improve intestinal ischemia |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100595/ https://www.ncbi.nlm.nih.gov/pubmed/33967762 http://dx.doi.org/10.3389/fphar.2021.629125 |
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