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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...

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Autores principales: Yan, Tao, Guo, Shun, Zhang, Tian, Zhang, Zhimin, Liu, An, Zhang, Song, Xu, Yuan, Qi, Yuhong, Zhao, Weihe, Wang, Qinhui, Shi, Lei, Liu, Linna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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