Djulis (Chenopodium formosanum), a pseudocereal crop native to Taiwan, is often utilized as a source of grain in the diet because of its high nutritional value. The hull of djulis is discarded as waste during cooking or processing because of its bitter taste. However, recent studies have shown that djulis hull possesses certain benefits, such as antioxidant, blood sugar-lowering, and gut microbiota-regulating properties. Herein, the gastroprotective activity of ethanolic extract of djulis hull (EEDH) against stomach injury caused by indomethacin (IND) in C57BL/6J mice and its mechanism of action was assessed. Preadministration of EEDH significantly attenuated the gastric ulcer caused by IND in a dose-dependent manner (p < 0.05). Additionally, gastric mucosal injury and gastric wall edema within the submucosal layer observed in histopathological examination were improved by administration of EEDH. EEDH preadministration also reinstated the reduction of glutathione (GSH) content and catalase (CAT), and superoxide dismutase (SOD) activities induced by IND, indicating that EEDH can modulate the antioxidant status of gastric mucosa in mice. Moreover, IND-induced decline of gastric COX-1 expression was upregulated in mice of EEDH treatment groups. Administration of IND increased the expression of proinflammatory proteins in the gastric mucosa of mice, including tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), whereas EEDH treatment significantly decreased their expression (p < 0.05). Consequently, EEDH can improve gastric injury by regulating antioxidant status and inhibiting proinflammatory signaling pathways, and has the potential to be developed as a functional food for gastric protection.

Contemporary pharmacological studies have reported that freshwater clam (Corbicula fluminea) can provide a broad spectrum of bioactivities, including antioxidant, anticancer, antihypertensive, hepatoprotective, and hypocholesterolemic effects. The aim of this study was to evaluate the gastroprotective effects of water extract of freshwater clam (WEC) on indomethacin (IND)-induced gastric mucosal cell damage in vitro and gastric ulcer in vivo. The cell viability of rat gastric mucosa RGM-1 cells was markedly decreased by 0.8 mM of IND treatment, and pre-treated with various concentration of WEC significantly restored IND-induced cell damage in a dose-dependent manner. WEC also significantly attenuated the elevated reactive oxygen species (ROS) levels, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and nuclear factor-κB (NF-κB) p65 nuclear translocation induced by IND. In the in vivo study, IND caused severe gastric ulcer in Wistar rats, while WEC pretreatment effectively reduced the ulcer area and edema in the submucosa. We found that WEC significantly restored glutathione (GSH) content in gastric mucosa in a dose-dependent manner (p < 0.05). The reduction of prostaglandin E2 (PGE2) caused by IND was also improved with higher doses of WEC administration. Moreover, the overexpression of COX-2, iNOS, and tumor necrosis factor-α (TNF-α) proteins in gastric mucosa was downregulated by administration of WEC. Consequently, WEC can be used as a potential nutritional supplement to improve NSAIDs-caused gastric mucosal lesions.