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This study examined the chemical profile and neuroprotective potential of\n                    <jats:italic>Echinocactus grusonii<\/jats:italic>\n                    spines and its endophytic fungus,\n                    <jats:italic>Aspergillus oryzae<\/jats:italic>\n                    . The spines contained markedly higher levels of phenolics (293\u00a0mg gallic acid\/g DW extract), flavonoids (132\u00a0mg quercetin\/g DW extract), and alkaloids (14.5\u00a0mg atropine\/g DW extract) compared to the stem. Untargeted metabolomics (UPLC-HRMS\/MS) tentatively identified 27 metabolites in the spines and 14 in the fungal extract. Both extracts exhibited potent, dose-dependent inhibition of acetylcholinesterase (AChE) and\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -secretase (BACE-1). The spines extract showed IC\u2085\u2080 values of 0.362\u00a0\u00b5g\/mL (AChE) and 0.425\u00a0\u00b5g\/mL (BACE-1), while the fungal extract was more effective against AChE (IC\u2085\u2080 = 0.255\u00a0\u00b5g\/mL). In silico docking was performed for all identified compounds, and molecular dynamics simulation of the top-scoring candidates demonstrated stable interactions with the target enzymes. These findings highlight the spines of\n                    <jats:italic>Echinocactus grusonii<\/jats:italic>\n                    and their associated endophytes as promising dual-target neuroprotective sources for the management of neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-62565-5","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:25:17Z","timestamp":1785324317000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic potential of Echinocactus grusonii and its associated endophytic fungus Aspergillus oryzae in neuroprotection: in vitro and in silico investigations"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-9860","authenticated-orcid":false,"given":"Ahmed A.","family":"Heraiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-7621","authenticated-orcid":false,"given":"Ahmed","family":"Othman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Farouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8975-9424","authenticated-orcid":false,"given":"Mostafa M.","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5554-9602","authenticated-orcid":false,"given":"Abd El-Salam I.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6746-4282","authenticated-orcid":false,"given":"Atef A.","family":"El-Hela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"62565_CR1","doi-asserted-by":"publisher","first-page":"49178","DOI":"10.1039\/D5RA07497E","volume":"15","author":"AA Heraiz","year":"2025","unstructured":"Heraiz, A. 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