Mechanism of Yinxu Weitong Capsule in the treatment of precancerous lesions of gastric cancer based on network pharmacology and experimental validation.

Ethnopharmacological Relevance: Yinxu Weitong Capsule (YXWTC) is a Chinese patent medicine used to treat chronic gastritis. However, its efficacy and mechanisms of action in treating precancerous lesions of gastric cancer (PLGC) remain unclear.

Aim Of The Study: To evaluate the effects of YXWTC on PLGC and explore the underlying mechanisms.

Materials And Methods: YXWTC components were identified using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole-exactive orbitrap mass spectrometry. A PLGC animal model was established and the protective effects of YXWTC on the gastric mucosa in PLGC rats were evaluated using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff and Alcian blue-high iron diamine staining, and transmission electron microscopy (TEM). The vital organs of the rats were examined using H&E staining to evaluate biosafety. Network pharmacology identified potential targets and pathways of YXWTC in PLGC treatment, followed by molecular docking validation. Various techniques, including enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, Western blotting, immunohistochemistry, apoptosis detection, and reactive oxygen species fluorescence staining were employed to elucidate the underlying mechanisms.

Results: In total, 340 YXWTC components were identified. YXWTC effectively improves gastric mucosal pathology in rats with PLGC. Network pharmacology identified 403 targets common to PLGC and YXWTC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified 2,323 biological processes and 206 signaling pathways, respectively. Molecular docking revealed that the primary target proteins and major drug molecules exhibited strong binding affinities. Animal studies demonstrated that YXWTC inhibited the IL-6/STAT3 pathway, promoted mitochondrial apoptosis, and induced ROS release.

Conclusions: We verified the pharmacodynamic effects of YXWTC in PLGC. In summary, the effects are mediated by inhibition of the IL-6/STAT3 pathway, promotion of mitochondrial apoptosis, and induction of ROS release.