Gastroprotective Effects of <i>Artemisia annua</i> L., on an Hydrochloric Acid/Ethanol-Induced Acute Gastritis Model via Anti-Oxidative and Anti-Inflammatory Activities

SPB-201, a water extract of <i>Artemisia annua</i> L., was investigated for its gastroprotective effects against hydrochloric acid/ethanol-induced gastric mucosal injury in rats and oxidative stress-induced damage in gastric cell models, with a focus on the mechanisms underlying its antioxidant and anti-inflammatory activity. Sprague-Dawley rats pretreated with SPB-201 (50 mg/kg) showed significantly reduced gastric lesion areas, improved histological architecture, modestly decreased gastric acid secretion, and increased gastric pH compared to non-treated controls. SPB-201 significantly restored antioxidant capacity by elevating glutathione (GSH) and superoxide dismutase levels while reducing malondialdehyde levels, a marker of lipid peroxidation. SPB-201 also suppressed the mRNA and protein expression of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase, indicating anti-inflammatory effects. Most notably, SPB-201 reduced the nuclear translocation of the NF-κB p65 subunit, thereby preventing NF-κB activation. In human gastric adenocarcinoma cells, SPB-201 improved cell viability and upregulated the expression of key antioxidant genes, including heme oxygenase-1, glutamate-cysteine ligase catalytic, and glutamate-cysteine ligase modifier subunits. In LPS-stimulated RAW 264.7 macrophages, SPB-201 significantly reduced the gene expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β (IL1β), and IL6. The findings demonstrated that SPB-201 enhances GSH-dependent antioxidant defenses and attenuates oxidative stress-induced inflammation, thereby protecting gastric mucosal integrity. SPB-201 might serve as a promising natural therapeutic agent for the prevention and treatment of gastric mucosal injuries associated with oxidative damage, such as gastritis and peptic ulcer disease.