Gastroprotective effects of a dietary Petasites japonicus ethanol extract against indomethacin-induced gastric injury via regulation of mucosal defense, acid secretion-related targets, and inflammation

Petasites japonicus (PJ) is a widely consumed traditional edible plant known for its anti-inflammatory and antioxidant properties; however, its protective role against non-steroidal anti-inflammatory drug (NSAID)-induced gastric injury has not been fully elucidated. This study evaluated the gastroprotective effects of ethanol-extracted PJ in vitro and in vivo using indomethacin-induced gastric ulcer models. High-performance liquid chromatography (HPLC) analysis demonstrated that the 50% ethanol extract contained higher levels of marker compound fukinolic acid (FKA), phenolic acids, and total polyphenols than the water extract. In vitro , PJ extract significantly improved cell viability and preserved mucosal defense by maintaining mucin 5AC (MUC5AC) expression against indomethacin-induced damage. Furthermore, PJ effectively suppressed the gastric acid secretion-related genes histamine H2 receptor ( HRH2 ) and H + /K + -ATPase isoforms ( ATP4A and ATP4B ), and inhibited the mitogen-activated protein kinases (MAPK) and inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling cascade, as evidenced by the collective downregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p-NF-κB, and p-IκB-α expression. In vivo , histological analysis and ulcer index evaluation demonstrated that PJ significantly attenuated gastric mucosal injury in the indomethacin-induced gastric ulcer rat model. PJ also restored MUC5AC expression and suppressed ATP4/histamine pathway, MAPK/NF-κB/iNOS/COX-2 signaling, and inflammatory markers (nitric oxide and tumor necrosis factor-α [TNF-α]). Additionally, molecular docking simulations predicted stable interactions of chlorogenic acid (CGA) and FKA with molecular targets associated with gastric acid secretion and inflammatory responses. Collectively, these findings demonstrate that PJ extract exerts significant gastroprotective effects by enhancing mucosal defense, modulating acid secretion-related genes, and attenuating inflammation. Collectively, these results underscore the potential of PJ extract as a promising natural functional food ingredient for the prevention and management of NSAID-induced gastric ulcers.