Yadav_2026_J.Ethnopharmacol_360_121178

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a neurodegenerative disease wherein loss of memory and cognition is very common. Oxidative stress, lack of acetylcholine, and inflammation in brain tissues are characteristics of AD. Development of natural remedies such as medicinal plants for management of AD is a viable strategy. AIM OF THE STUDY: In the present study, methanolic extract of Oxalis corniculata (MEOC) was examined for its beneficial role in management of AD by integrating in vitro and in silico experiments. MATERIALS AND METHODS: MEOC was prepared from the leaves of O. corniculata, analyzed for total phenolic and flavonoid content, and subjected to GCMS and LC/MS-MS analyses for identification of various chemical compounds. The identified compounds were screened for antioxidant and cholinesterase inhibition potential by molecular docking analysis. In vitro antioxidant activity by free radical scavenging assay (DPPH assay), acetylcholinesterase (AChE) inhibition, and cytotoxicity in SHSY-5Y cells by MTT assay, of MEOC was evaluated. Furthermore, measurement of reactive oxygen species (ROS), NF-kB inhibition, level of glutathione, superoxide dismutase (SOD), malonaldehyde (MDA) and catalase in MEOC treated Lipopolysaccharide (LPS)-stimulated SHSY-5Y cells was also determined. RESULTS: MEOC contained 41.22 mg of GAE/g and 82.12 mg of QE/g of MEOC of total phenolics and flavonoids, respectively. GCMS analysis revealed the presence of 48 compounds in MEOC, and LC/MS-MS analysis confirmed the presence of 18 phenolic acids and 15 flavonoids. MEOC did not show significant neurotoxicity in SHSY-5Y cells up to a dose of 1200 microg/mL but possessed prominent antioxidant and acetylcholinesterase inhibition property. MEOC significantly reduced the level of ROS, NF-kB and MDA, however, the level of glutathione, SOD and catalase increased significantly in LPS-stimulated SHSY-5Y cells. Molecular docking studies were performed against the targets 4EY7 (AChE receptor), 4TPK (butyrylcholinesterase, BuChE receptor), and 2BXK (antioxidant receptor). Among the compounds identified through GC-MS analysis, squalene exhibited the highest docking scores across all targeted proteins. In contrast, among the flavonoids identified by LC-MS, rutin showed the strongest binding affinities toward the active sites of 4EY7 and 4TPK, with LibDock scores of 144.525 and 148.499, respectively, whereas myricetin recorded the highest docking score (125.097) against 2BXK. Among the phenolic acids identified by LC-MS, chlorogenic acid exhibited the highest binding affinities for AChE and BuChE, with docking scores of 130.868 (4EY7) and 125.387 (4TPK), respectively, while ferulic acid showed the strongest binding affinity toward the antioxidant receptor 2BXK. CONCLUSION: The findings indicate that MEOC is a rich source of phytoconstituents having antioxidant and cholinesterase inhibitory properties and may be useful in circumventing AD. It can be concluded that the leafy vegetable, O. corniculata is beneficial in AD and may be explored in the future for its mechanism of action through in vivo studies.