College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China.
Drug Des Devel Ther. 2024 May 17;18:1651-1672. doi: 10.2147/DDDT.S454758. eCollection 2024.
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.
This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism.
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.
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.
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.
左金丸（ZJP）在临床实践中广泛用于治疗慢性萎缩性胃炎（CAG），有效改善患者呕吐、疼痛和腹胀等症状。然而，ZJP 治疗 CAG 的潜在机制尚未完全阐明。
本研究旨在阐明 ZJP 治疗 CAG 的特征功能及其潜在机制。
采用交替给予氨溶液和脱氧胆酸钠以及不规则饮食的方法建立 CAG 模型。分析 ZJP 对体重、血清生化指标和一般情况的治疗效果。通过 HE 染色和 AB-PAS 染色分析胃黏膜损伤和胃黏膜厚度的特征。此外，采用网络药理学和分子对接预测 ZJP 治疗 CAG 的调节机制和主要活性成分。采用 RT-PCR、免疫组化、免疫荧光和 Western blot 测定凋亡相关蛋白、胃黏膜屏障相关蛋白和 PI3K/Akt 信号通路蛋白的表达水平。
结果表明，ZJP 显著改善 CAG 大鼠的一般状态，减轻体重减轻和胃组织学损伤，并降低血清生化指标。网络药理学和分子对接发现，ZJP 通过抑制炎症、抑制细胞凋亡和通过 PI3K/Akt 信号通路保护胃黏膜屏障来治疗 CAG。进一步的实验证实，ZJP 明显调节胃黏膜细胞凋亡相关关键蛋白的表达，如 Bax、Bad、Apaf-1、cleaved-caspase-3、cleaved-caspase-9、Cytochrome C、Bcl-2 和 Bcl-xl。此外，ZJP 显著逆转 Occludin、ZO-1、Claudin-4 和 E-cadherin 的蛋白表达。
本研究表明，ZJP 通过抑制 PI3K/Akt 信号通路治疗 CAG。本研究为 ZJP 在临床实践中的合理应用提供了科学依据。
