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The stress resistance and antiaging potential of AR and BME were assessed in wild\u2010type N2 and transgenic <jats:italic>C. elegans<\/jats:italic> strains CF1553, TJ356, and BA17. Transgenic CL4176 expressing the human amyloid\u2010beta peptide (A\u03b2) was used as a model for A\u03b2 toxicity, whereas transgenic AM141 expressing polyQ aggregates was employed as a model for Huntington's disease. An in silico molecular docking study using Discovery Studio 4.5 was performed to elucidate the putative binding mode of BME to the active sites of Daf\u20102 protein, involved in longevity and oxidative stress resistance in <jats:italic>C. elegans<\/jats:italic>. BME and AR significantly delayed the appearance of oxidative stress markers in wild\u2010type N2 and transgenic strains TJ356 and CF1553, affecting the DAF\u201016\/FOXO transcription factor subcellular distribution and inducing expression of the <jats:italic>sod\u20103<\/jats:italic> antioxidative gene. Pretreatment with AR significantly reduced the aging marker lipofuscin accumulation in BA17 worms, its effect was greater than that of epigallocatechin gallate, suggesting a potential antiaging effect. Neuroprotective effects of AR and BME were confirmed in AM141 transgenic worms, inducing a significant reduction in the score of polyQ40::GFP aggregates. Moreover, BME (25\u2009\u00b5g\/mL) resulted in a significant delay in A\u03b2\u2010induced paralysis in CL4176 worms. In silico molecular modeling revealed that BME exhibited good fitting scores within the active sites of the Daf\u20102 protein. AR and BME exert beneficial effects in the modulation of age\u2010related markers and attenuation of neurotoxicity in neurodegenerative disorders. Hence, AR and BME could be recognized as promising antioxidant and neuroprotective natural drug candidates that could be included in neuro\u2010nutraceuticals.<\/jats:p>","DOI":"10.1002\/ardp.202400464","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T13:50:27Z","timestamp":1727963427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Stress resistance, antiaging, and neuroprotective activities of baicalein 5,6\u2010dimethyl ether and <i>Alnus rugosa<\/i> extract in <i>Caenorhabditis elegans<\/i> model"],"prefix":"10.1002","volume":"357","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-8241","authenticated-orcid":false,"given":"Iriny M.","family":"Ayoub","sequence":"first","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-0560","authenticated-orcid":false,"given":"Omayma A.","family":"Eldahshan","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy Ain Shams University Cairo Egypt"},{"name":"Centre for Drug Discovery Research and Development Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Roxo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology Heidelberg University Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoxiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology Heidelberg University Heidelberg Germany"},{"name":"College of Horticulture Fujian Agriculture and Forestry University Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Wink","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology Heidelberg University Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel Nasser B.","family":"Singab","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy Ain Shams University Cairo Egypt"},{"name":"Centre for Drug Discovery Research and Development Ain Shams University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"issue":"7","key":"e_1_2_9_2_1","first-page":"515","volume":"51","author":"Pandey R.","year":"2013","journal-title":"Indian J. 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