1. Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.
- Author
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Chen L, He T, Wang R, Liu H, Wang X, Li H, Jing M, Zhou X, Wei S, Zou W, and Zhao Y
- Subjects
- Animals, Rats, Male, Chronic Disease, Signal Transduction drug effects, Phosphatidylinositol 3-Kinases metabolism, Apoptosis drug effects, Network Pharmacology, Proto-Oncogene Proteins c-akt metabolism, Gastritis, Atrophic drug therapy, Gastritis, Atrophic pathology, Gastritis, Atrophic metabolism, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal chemistry, Gastric Mucosa drug effects, Gastric Mucosa pathology, Gastric Mucosa metabolism, Disease Models, Animal, Molecular Docking Simulation, Rats, Sprague-Dawley
- Abstract
Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated., Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism., Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins., Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin., Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Chen et al.)
- Published
- 2024
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