Zhiyong Jiao,1,2,* Jia Zheng,1,2,* Xinyu Yang,1,2 Qin Ruan,1,2 Yuhan Ma,3 Yuzhe Huang,1,4 Cheng Jin,1,4 Shuangying Gui,1,4 Zihua Xuan,1 Juan Liang,1 Xiaoyi Jia1,2 

1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, People’s Republic of China; 3Hefei China Resources Shenlu Pharmaceutical Co. Ltd, Hefei, Anhui, 230012, People’s Republic of China; 4Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230012, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiaoyi Jia, School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China, Tel +86 0551 68129186, Email jiaxy@ahtcm.edu.cn Juan Liang, School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China, Email Ljuan@ahtcm.edu.cn

Background: Chronic atrophic gastritis of stomach yin deficiency syndrome (YDCAG) is a precancerous lesion characterized by inflammation of gastric mucosa and atrophy of gastric adenocytes. Yangweishu (YWS) is widely used to treat gastrointestinal diseases.
Objective: This study was to investigate the mechanism of YWS in YDCAG.
Methods: The YDCAG rat model was established using a comprehensive modeling approach, and a human gastric epithelial cell (GES-1) injury model was induced by MNNG stimulation. Hematoxylin-eosin staining (HE), enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (RT-PCR), immunohistochemistry and Western blotting were performed to observe the effects of YWS on YDCAG rats and GES-1 cells. Network pharmacology was conducted to identify potential core targets and signaling pathways involved in the anti-YDCAG effects of YWS. RT-PCR and Western blotting were employed to measure the gene and protein expression in the IL-6/STAT3 signaling pathway in vivo and in vitro. Apoptosis in GES-1 cells was evaluated through flow cytometry, immunofluorescence, RT-PCR, and Western blotting.
Results: YWS significantly improved gastric morphology in YDCAG rats and alleviated GES-1 cell injury induced by MNNG. YWS treatment also reduced serum, tissue, and cellular levels of inflammatory cytokines, while enhancing antioxidant capacity. Network pharmacology analysis suggested that YWS modulates apoptosis and inhibits the IL-6/STAT3 signaling pathway. Furthermore, YWS has an ameliorative effect on apoptosis and inhibits the expression of IL-6/STAT3 signaling pathway genes and proteins in vitro and in vivo.
Conclusion: YWS has a good therapeutic effect on YDCAG, which may be closely related to the inhibition of IL-6/STAT3 signaling pathway.

Keywords: Yangweishu, chronic atrophic gastritis with stomach yin deficiency syndrome, network pharmacology, IL-6/STAT3 signaling pathway, cell apoptosis