RGD Reference Report - Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH4/eNOS to Improve Intestinal Ischemia. - Rat Genome Database

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Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH4/eNOS to Improve Intestinal Ischemia.

Authors: Yan, Tao  Guo, Shun  Zhang, Tian  Zhang, Zhimin  Liu, An  Zhang, Song  Xu, Yuan  Qi, Yuhong  Zhao, Weihe  Wang, Qinhui  Shi, Lei  Liu, Linna 
Citation: Yan T, etal., Front Pharmacol. 2021 Apr 22;12:629125. doi: 10.3389/fphar.2021.629125. eCollection 2021.
RGD ID: 329961325
Pubmed: PMID:33967762   (View Abstract at PubMed)
PMCID: PMC8100595   (View Article at PubMed Central)
DOI: DOI:10.3389/fphar.2021.629125   (Journal Full-text)

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/BH4/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 BH4 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/BH4/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GCH1Humanintestinal disease treatmentISOGch1 (Rattus norvegicus)associated with Experimental Radiation InjuriesRGD 
Gch1Ratintestinal disease treatmentIEP associated with Experimental Radiation InjuriesRGD 
Gch1Mouseintestinal disease treatmentISOGch1 (Rattus norvegicus)associated with Experimental Radiation InjuriesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gch1  (GTP cyclohydrolase 1)

Genes (Mus musculus)
Gch1  (GTP cyclohydrolase 1)

Genes (Homo sapiens)
GCH1  (GTP cyclohydrolase 1)


Additional Information