Wendan Decoction ameliorates MNNG-induced chronic atrophic gastritis via the JAK2/STAT3 signaling pathway

Wendan Decoction (WDD) is a classical prescription deeply rooted in traditional Chinese medicine (TCM), originally documented by Sun Simiao in Beiji Qianjin Yaofang during the Tang Dynasty. Traditionally, it has been used to treat disorders associated with phlegm-dampness accumulation and digestive dysfunction, reflecting the TCM principle of harmonizing the stomach and resolving dampness. Within the clinical practice at Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, WDD is employed for the treatment of chronic atrophic gastritis (CAG), continuing its long-standing application in gastrointestinal disorders. Despite its widespread traditional use and cultural significance, the active constituents and precise pharmacological mechanisms of WDD have not yet been fully elucidated.

This study aimed to systematically investigate the material basis and therapeutic mechanisms of WDD in CAG treatment.

The bioactive constituents of WDD were first identified using high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS). To evaluate its therapeutic effects, we established both in vivo and in vitro models of chronic atrophic gastritis (CAG). For the in vivo studies, a rat CAG model was generated through a multi-factor compound induction approach, whereas in vitro cellular injury was induced using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). To elucidate the underlying mechanisms, we integrated network pharmacology to predict candidate targets and signaling pathways, followed by experimental verification via immunohistochemical staining and Western blot analysis.

HPLC-Q-TOF-MS/MS profiling revealed 34 bioactive constituents in WDD, with naringin, neohesperidin, and narirutin identified as key components. In vivo investigations demonstrated that WDD administration markedly improved gastric histopathological alterations in CAG model rats, accompanied by increased serum levels of pepsinogen I (PG I) and pepsinogen II (PG II), along with reduced gastrin-17 (G-17) and interleukin-6 (IL-6) concentrations. In vitro studies further showed that WDD treatment inhibited cell proliferation, migration, and invasive potential in MNNG-transformed MC cells. Network pharmacology-based analysis predicted that the therapeutic efficacy of WDD against CAG was primarily mediated via the JAK/STAT signaling axis. Subsequent mechanistic validation confirmed that WDD significantly attenuated the phosphorylation of JAK2 and STAT3, suggesting its inhibitory effect on the JAK2/STAT3 pathway.

This study revealed that WDD exerted therapeutic effects on CAG through suppression of the JAK2/STAT3 pathway. Our findings elucidate the pharmacological mechanisms of WDD and provide a scientific basis for its traditional use in managing CAG, highlighting its potential as a therapeutic candidate worthy of further clinical investigation.