{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:11:33Z","timestamp":1790878293592,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bowen University","award":["BURG\/2024\/006"],"award-info":[{"award-number":["BURG\/2024\/006"]}]},{"name":"Bowen University","award":["RSPD2024R965"],"award-info":[{"award-number":["RSPD2024R965"]}]},{"name":"King Saud University (Riyadh, Saudi Arabia)","award":["BURG\/2024\/006"],"award-info":[{"award-number":["BURG\/2024\/006"]}]},{"name":"King Saud University (Riyadh, Saudi Arabia)","award":["RSPD2024R965"],"award-info":[{"award-number":["RSPD2024R965"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is an age-associated neurodegenerative condition marked by amyloid plaques, synaptic dysfunction, and neuronal loss. Besides conventional medical care, herbal therapies, both raw and refined, have attracted researchers for their potential therapeutic effects. As a proof-of-concept, our study combined HPLC-DAD analysis of bioactive constituents, network pharmacology, molecular dynamics (MD), molecular docking, post-MD analysis, and experimental verification to investigate the mechanisms of crude drug formulations as a therapeutic strategy for AD. We identified nine bioactive compounds targeting 188 proteins and 1171 AD-associated genes. Using a Venn diagram, we found 47 overlapping targets, forming \u201cherb-compound-target (HCT)\u201d interaction networks and a protein\u2012protein interaction (PPI) network. Simulations analyzed binding interactions among the three core targets and their compounds. MD assessed the stability of the best-ranked poses and beneficial compounds for each protein. Among the top 22 hub genes, AChE, BChE, and MAO, ranked 10, 14, and 34, respectively, were selected for further analysis. Two tetraherbal formulations, Form A and Form B, showed notable activity against AChE. Form A exhibited significant (p &lt; 0.0001) inhibitory activity (IC50 = 114.842 \u00b1 2.084 \u00b5g\/mL) compared to Form B (IC50 = 142.829 \u00b1 4.258 \u00b5g\/mL), though weaker than galantamine (IC50 = 27.950 \u00b1 0.122 \u00b5g\/mL). Form B had significant inhibitory effects on BChE (IC50 = 655.860 \u00b1 32.812 \u00b5g\/mL) compared to Form A (IC50 = 679.718 \u00b1 20.656 \u00b5g\/mL), but lower than galantamine (IC50 = 23.126 \u00b1 0.683 \u00b5g\/mL). Both forms protected against Fe2+-mediated brain injury by inhibiting MAO. Docking identified quercetin (\u221210.2 kcal\/mol) and myricetin (\u221210.1 kcal\/mol) for AChE; rutin (\u221210.6 kcal\/mol) and quercetin (\u22129.7 kcal\/mol) for BChE; and kaempferol (\u22129.1 kcal\/mol) and quercetin (\u22128.9 kcal\/mol) for MAO. These compounds were thermodynamically stable based on MD analysis. Collectively, the results offer a scientific rationale for the use of these specifically selected medicinal herbs as AD medications.<\/jats:p>","DOI":"10.3390\/life14101222","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T04:01:24Z","timestamp":1727236884000},"page":"1222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Network Pharmacology, Molecular Dynamics and In Vitro Assessments of Indigenous Herbal Formulations for Alzheimer\u2019s Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-396X","authenticated-orcid":false,"given":"Oluwafemi Adeleke","family":"Ojo","sequence":"first","affiliation":[{"name":"Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 232102, Nigeria"},{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-2497","authenticated-orcid":false,"given":"Omolola Adenike","family":"Ajayi-Odoko","sequence":"additional","affiliation":[{"name":"Microbiology Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-1739","authenticated-orcid":false,"given":"Gideon Ampoma","family":"Gyebi","sequence":"additional","affiliation":[{"name":"Natural Products and Structural (Bio-Chem)-Informatics Research Laboratory (NpsBC-RI), Department of Biochemistry, Bingham University, Karu 961105, Nigeria"},{"name":"Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damilare IyinKristi","family":"Ayokunle","sequence":"additional","affiliation":[{"name":"Pure and Applied Biology Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-846X","authenticated-orcid":false,"given":"Akingbolabo Daniel","family":"Ogunlakin","sequence":"additional","affiliation":[{"name":"Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 232102, Nigeria"},{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Henry","family":"Ezenabor","sequence":"additional","affiliation":[{"name":"Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 232102, Nigeria"},{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-4465","authenticated-orcid":false,"given":"Adesoji Alani","family":"Olanrewaju","sequence":"additional","affiliation":[{"name":"Chemistry and Industrial Chemistry Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatobi Deborah","family":"Agbeye","sequence":"additional","affiliation":[{"name":"Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 232102, Nigeria"},{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel Tope","family":"Ogunwale","sequence":"additional","affiliation":[{"name":"Animal Science Programme, Bowen University, Iwo 232102, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3721-8065","authenticated-orcid":false,"given":"Damilare Emmanuel","family":"Rotimi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Department of Biochemistry, Landmark University, Omu-Aran 251101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Fouad","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-425X","authenticated-orcid":false,"given":"Gaber El-Saber","family":"Batiha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutic, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluyomi Stephen","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 232102, Nigeria"},{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria"},{"name":"Laboratory of Sustainable Animal Environment Systems, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8579, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jtcme.2020.08.002","article-title":"Identification of phytochemicals from North African plants for treating Alzheimer\u2019s diseases and of their molecular targets by in silico network pharmacology approach","volume":"11","author":"Raafat","year":"2020","journal-title":"J. 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