From plant pair to gastroprotection: chemical standardization and in vivo validation of Akebiae Fructus-Hoveniae semen against ethanol-mediated mucosal damage.

Abstract

OBJECTIVES: The present study sought to elucidate the gastroprotective mechanism of the Akebiae Fructus- Hoveniae Semen combination by integrating chemical fingerprinting, network pharmacology and in vivo validation. METHODS: High-performance liquid chromatography (HPLC) fingerprints were established for 13 pairs of drug combinations. Core targets and pathways were predicted using network pharmacology and subsequently validated. in a mouse model of ethanol-induced acute gastric mucosal injury. KEY FINDINGS: HPLC fingerprinting revealed eight characteristic components. Network pharmacology analysis identified 29 hub targets (e.g. interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP9) and B-cell lymphoma 2 (BCL2)) implicated in the interleukin-17 (IL-17), mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signalling pathways. In vivo, the treatment combination demonstrated a dose-dependent reduction in gastric damage. It significantly decreased the elevated levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and malondialdehyde (MDA), while restoring interleukin-10 (IL-10) levels and superoxide dismutase (SOD) activity. The high-dose treatment exerted the most potent effects. CONCLUSIONS: The combination exerts a potent protective effect against ethanol-induced gastric mucosal injury in mice, likely mediated through the modulation of inflammatory cytokines, oxidative stress markers and key protein targets in a dose-dependent manner. These findings provide a basis for its traditional use in gastrointestinal disorders.