Green Phytochemical-Based Gastroprotection of Glucomannan against Indomethacin-Induced Gastric Ulcers via Cytoprotection and Anti-Apoptotic Effects

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used but frequently induce gastric mucosal injury. Indomethacin disrupts mitochondrial function, promotes cytochrome c release, and activates caspase-3, leading to apoptosis and epithelial damage. Systemic inhibition of cyclooxygenase-1 (COX-1) further reduces prostaglandin synthesis, compromising gastric mucosal defense. Current anti-ulcer therapies show limited efficacy and notable adverse effects, highlighting the need for safer gastroprotective alternatives. Glucomannan, a plant-derived polysaccharide, has demonstrated the ability to enhance COX-1 expression and suppress apoptotic activity. This study aimed to evaluate the protective effects of Amorphophallus oncophyllus-derived glucomannan against indomethacin-induced gastric ulceration in Wistar rats and to elucidate its cytoprotective, and anti-apoptotic mechanisms. Thirty male Wistar rats were randomly allocated into five groups (n = 6). Group 1 received vehicle only; Group 2 was administered a single oral dose of indomethacin (50 mg/kg). Groups 3-5 were pretreated orally with glucomannan (40, 80, or 160 mg/kg) for seven consecutive days, followed by indomethacin administration. Macroscopic gastric lesions were quantified, and immunohistochemical analyses for COX-1 and caspase-3 expression were performed. Indomethacin induced marked gastric damage characterized by inflammation, erosion, ulceration, and hemorrhage. Glucomannan pretreatment significantly attenuated these lesions in a dose-dependent manner, with 160 mg/kg exhibiting the strongest protective effect (ulcer inhibition rate: 80%). Glucomannan restored COX-1 expression while markedly reducing caspase-3 activity, demonstrating enhanced mucosal cytoprotection and reduced apoptosis. Amorphophallus oncophyllus glucomannan confers potent gastroprotective effects against indomethacin-induced gastric injury, mediated through the upregulation of COX-1 and suppression of caspase-3-dependent apoptosis. These findings suggest its potential as a natural, safe prophylactic agent for NSAID-associated gastric ulceration.