TY  - JOUR
T1  - Mechanistic Insights into Zuojin Pill in Chronic Atrophic Gastritis: Modulation of PI3K/Akt-Mediated Apoptosis and Gastric Mucosal Barrier Integrity
A1  - Hiroshi Nakamura
A1  - Yuta Kato
JF  - Pharmaceutical Sciences and Drug Design
JO  - Pharm Sci Drug Des
SN  - 3062-4428
Y1  - 2025
VL  - 5
IS  - 2
DO  - 10.51847/fEFfm72Jfa
SP  - 220
EP  - 242
N2  - In clinical practice, the Zuojin Pill (ZJP) is commonly used to manage chronic atrophic gastritis (CAG) and effectively alleviates symptoms such as emesis, discomfort, and abdominal bloating. Yet, the mechanistic basis for ZJP’s therapeutic action in CAG remains unclear. The objective of this work was to define the distinctive role of ZJP in CAG management along with its potential mode of action. An experimental CAG model was generated through alternating exposure to ammonia solution and sodium deoxycholate, together with erratic dietary intake. Evaluations were conducted on ZJP’s impact on body mass, serum biochemical parameters, and overall physiological status. Assessment of mucosal lesions and gastric mucosal depth was performed via HE staining and AB-PAS staining. Furthermore, network pharmacology, coupled with molecular docking, enabled the prediction of regulatory pathways and key bioactive constituents of ZJP relevant to CAG therapy. Quantification of molecules linked to apoptosis, gastric mucosal barrier integrity, and the PI3K/Akt signaling cascade was carried out using RT-PCR, immunohistochemistry, immunofluorescence, and Western blotting. Findings revealed that ZJP substantially improved overall physiological condition in CAG rats, attenuated body mass loss and gastric tissue pathology, and reduced serum biochemical markers. Network pharmacology and molecular docking analyses identified that ZJP targets CAG by suppressing inflammation, inhibiting apoptosis, and preserving the gastric mucosal barrier via the PI3K/Akt signaling pathway. Subsequent experimental validation confirmed that ZJP visibly regulated the levels of critical proteins governing gastric mucosal cell apoptosis, namely Bax, Bad, Apaf-1, cleaved caspase-3, cleaved caspase-9, cytochrome c, Bcl-2, and Bcl-xl. Additionally, ZJP markedly restored the protein abundance of Occludin, ZO-1, Claudin-4, and E-cadherin. This investigation demonstrated that ZJP exerts therapeutic effects on CAG by suppressing the PI3K/Akt signaling pathway, providing a scientific rationale for its appropriate clinical use.
UR  - https://galaxypub.co/article/mechanistic-insights-into-zuojin-pill-in-chronic-atrophic-gastritis-modulation-of-pi3kakt-mediated-6l1krkng5mmoqox
ER  -