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Context: Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with medicinal properties. However, the effects of A. rugosum on gastric ulcer remain unclear. Objective: To investigate the gastroprotective efficacy of water extract of A. rugosum (WEA) on gastric ulcer. Materials and methods: Sprague-Dawley rats were randomly grouped as control, model, lansoprazole and 200, 100 and 50 mg/kg of WEA. After pre-treatment for seven days, ethanol- and indomethacininduced gastric ulcer models were established. The gastric ulcer and histopathology were investigated. Enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (Q-PCR) and Western blot assays were conducted to explore the potential anti-inflammatory effect and mechanism of WEA. Additionally, the pyloric ligation model was used to explore the influence of WEA on gastric acid and mucus. Results: Pre-treatment with WEA (200, 100 and 50mg/kg) effectively reduced ulcerous area in both ethanol-induced (71%, 88% and 71%) and indomethacin-induced (77%, 65% and 86%) gastric ulcer model. The gastric levels of tumour necrosis factor-alpha (TNF-a) (34% and 50mg/kg), interleukin-6 (IL-6) (32% and 100mg/kg) and interleukin-1b (IL-1b) (36%, 45% and 41%) were reduced significantly (p<0.05) by WEA. Serum nitric oxide was decreased significantly (p<0.05) at 200 and 50mg/kg and PGE2 concentration was increased remarkably (p<0.05) at 100 mg/kg. Gene expression of inflammasome Nlrp3, and the nuclear translocation of nuclear factor-jB (NF-jB) P65 were significantly decreased by WEA pre-treatment. However, the pH of gastric acid and secretion of mucus did not show any significant change. Conclusions: The gastroprotective effect of WEA on gastric damage is attributed to anti-inflammation through the inhibition on NF-jB P65 nuclear migration and Nlrp3 gene expression. [ABSTRACT FROM AUTHOR]