Effect of Celastrus orbiculatus extract on gastric precancerous lesions through the regulation of the Notch-1 signaling pathway
10.19405/j.cnki.issn1000-1492.2025.02.018
- Author:
Junsong Wen
1
;
Ziwei Pan
2
;
Yanqing Liu
1
;
Yaodong Zhu
1
Author Information
1. ept of Integrative Medicine and Oncology , The First Afiliated Hospital of Anhui Medical University, Hefei 230022
2. Dept of Traditional Chinese Medicine , The Afiliated Hospital of Yangzhou University , Yangzhou 225009
- Publication Type:Journal Article
- Keywords:
Celastrus orbiculatus extract;
gastric precancerous lesions;
Notch-1 signaling pathway;
leucine-rich repeat-containing G-protein coupled receptor 5;
mucin
- From:
Acta Universitatis Medicinalis Anhui
2025;60(2):313-320
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To observe the effect of Celastrus orbiculatusextract(COE) on gastric precancerous lesions(GPL) and to explore its role in the Notch-1 signaling pathway.
Methods :GPL rat models were established using a composite model replication method, and the rats were randomly divided into a control group, a model group, and COE low, medium and high dose groups [COE at 12.5, 25, and 50 mg/(kg·d)]. After 4 weeks of intervention, gastric tissue was collected, and immunohistochemistry(IHC) was performed to detect the expression of mucins(MUC2, MUC5AC, and MUC6), Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5), Proliferating Cell Nuclear Antigen(Ki67), and Notch-1. Polymerase chain reaction(PCR) was used to determine the mRNA levels of the aforementioned mucins. Human gastric epithelial cells(GES-1) were induced with N-Methyl-N′-nitro-N-nitrosoguanidine(MNNG) to establish a GPL cell model. The cells were randomly divided into control, model, and COE low, medium, and high concentration groups(COE at 5, 10, and 20 μg/ml). After 24 hours of corresponding interventions, changes in cell morphology were observed under an inverted microscope. Western blot was used to measure the expression of Notch-1 and Lgr5, and immunofluorescence(IF) was employed to detect Notch-1 expression.
Results :Compared to the control group, the expression of MUC2, Lgr5, Notch-1, and Ki67 in the gastric tissue of the model group rats significantly increased(P<0.000 1), while the expression of MUC5AC and MUC6 decreased(P<0.000 1). In comparison to the model group, the expressions of MUC2, Lgr5, Notch-1, and Ki67 were significantly reduced in the COE groups(P<0.01), while the expression of MUC5AC and MUC6 significantly increased(P<0.01). In the GES-1 model group, the cells exhibited irregular morphology, loose intercellular connections, and disorganized arrangement compared to the control group. In contrast, the cells in the COE groups displayed a more regular morphology and a more organized arrangement than those in the model group. Additionally, compared to the control group, the expression of Lgr5 and Notch-1 in the model group were significantly elevated(P<0.000 1), whereas after COE treatment, their expressions were markedly reduced(P<0.001).
Conclusion:COE can alleviate GPL, and its mechanism may be associated with the downregulation of the Notch-1 signaling pathway, which improves gastric mucosal mucin barrier function and inhibits the abnormal proliferation of gastric mucosal stem cells.
- Full text:2026012211223978682南蛇藤提取物通过调控Not...信号通路对胃癌前病变的影响_文俊凇.pdf
