Investigation of the putative mechanism by which Ferula sinkiangensis leaves alleviate functional Dyspepsia-like symptoms in rats via modulation of the NO/cGMP/PKG signaling pathway.

Functional dyspepsia (FD) is a common functional gastrointestinal disorder with limited therapeutic options that often cause adverse effects. Ferula sinkiangensis (F. sinkiangensis) leaves have been used traditionally in Xinjiang, China, to relieve gastrointestinal complaints, yet their pharmacodynamic efficacy, active constituents, and molecular mechanisms against FD remain poorly defined. In a prior study, we detected 23 systemically absorbed prototype components of F. sinkiangensis leaf aqueous extract (FSLAE) in rats by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Building on those results, the present study assessed FSLAE's potential therapeutic effects against FD and investigated its molecular mechanisms based on the previously characterized components. We applied network pharmacology to identify putative core active ingredients, hub targets, and relevant signaling pathways, and then used molecular docking to predict binding interactions between core ingredients and key targets. Finally, we evaluated FSLAE's pharmacodynamic effects and mechanisms in a rat model of FD induced by iodoacetamide plus chronic tail-clamping stress. Network pharmacology highlighted the NO/cGMP/PKG pathway as a likely principal regulatory route, and five core ingredients showed favorable predicted binding affinities for eNOS and PKG1. FSLAE increased gastrointestinal motility in a dose-dependent manner, reduced gastric mucosal injury, restored gastrointestinal hormone balance, and lowered inflammatory cytokine levels in FD model rats. These effects correlated with suppression of aberrant activation of the NO/cGMP/PKG signaling pathway. Together, the findings indicate that FSLAE has therapeutic potential against FD, at least in part by modulating NO/cGMP/PKG signaling. This study therefore provides preliminary scientific support for the traditional use of F. sinkiangensis leaves and identifies FSLAE as a potential novel candidate for FD management.