Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation

作者：Lan Liang, Chenming He, Xue Han, Jia Liu, Liuhong Yang, Fengjiao Chang, Yami Zhang, Jie Lin · 发表于：Drug Design Development and Therapy · 年份：2024 · DOI：10.2147/dddt.s487371 · 被引用次数：13 · 研究领域：Computational Drug Discovery Methods、Cytokine Signaling Pathways and Interactions、Curcumin's Biomedical Applications

Background: Precancerous lesions of gastric cancer (PLGC) represent critical stages in gastric cancer progression, with a high risk of malignancy. Current treatments, such as Helicobacter pylori eradication, show limited efficacy in reversing precancerous molecular changes. Zuojin Pill (ZJP), a traditional Chinese medicine, has demonstrated potential for treating digestive disorders and may offer a promising approach for PLGC intervention. Objective: This study aims to investigate the therapeutic effects and mechanisms of ZJP in treating PLGC, focusing on its active components, target pathways, and molecular interactions. By using advanced analytical techniques, we provide a scientific foundation for ZJP's potential application in early gastric cancer intervention. Methods: Using ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), we identified active components in ZJP. A network pharmacology approach was then applied to construct a "ZJP-compound-target-disease" network. Molecular docking and molecular dynamics simulations were conducted to analyze the stability and interactions of the main active components of ZJP with core protein targets in PLGC. Animal experiments were used to validate significant targets and pathways in vivo. Results: Tangeritin, Isorhamnetin, Caffeic Acid, Azelaic Acid, and Adenosine were identified as the main active components of ZJP in the treatment of PLGC, with key targets inclu...