{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:24:31Z","timestamp":1778786671377,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Salman Center for Disability Research","award":["KSRG-2023-562"],"award-info":[{"award-number":["KSRG-2023-562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Down Syndrome (DS), characterized by trisomy of chromosome 21, leads to the overexpression of several genes contributing to various pathologies, including cognitive deficits and early-onset Alzheimer\u2019s disease. This study aimed to identify the intersection genes of two polyphenolic compounds, apigenin and naringenin, and their potential therapeutic targets in DS using network pharmacology. Key proteins implicated in DS, comprising DYRK1A, APP, CBS, and ETS2, were selected for molecular docking and dynamics simulations to assess the binding affinities and stability of the protein\u2013ligand interactions. Molecular docking revealed that naringenin exhibited the highest binding affinity to DYRK1A with a score of \u22129.3 kcal\/mol, followed by CBS, APP, and ETS2. Moreover, molecular docking studies included positive control drugs, such as lamellarin D, valiltramiprosate, benserazide, and TK216, which exhibited binding affinities ranging from \u22125.5 to \u22128.9 kcal\/mol. Apigenin showed strong binding to APP with a score of \u22128.8 kcal\/mol, suggesting its potential in modulating amyloid-beta levels. These interactions were further validated through molecular dynamics simulations, demonstrating stable binding throughout the 100 ns simulation period. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses indicated minimal fluctuations, confirming the stability of the complexes. The findings suggest that apigenin and naringenin could serve as effective therapeutic agents for DS by targeting key proteins involved in its pathology. Future studies should focus on in vivo validation, clinical trials, and exploring combination therapies to fully harness the therapeutic potential of these compounds for managing DS. This study underscores the promising role of network pharmacology in identifying novel therapeutic targets and agents for complex disorders like DS.<\/jats:p>","DOI":"10.3390\/ph17081090","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-5680","authenticated-orcid":false,"given":"Mohd","family":"Amir","sequence":"first","affiliation":[{"name":"Department of Natural Products, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shabana","family":"Shafi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, College of Computer Science and Engineering, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahida","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Nursing, College of Pharmacy and Applied Medical Sciences (CPAMS), Dar Al Uloom University, Riyadh 13314, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0795-2835","authenticated-orcid":false,"given":"Aijaz Ahmad","family":"Reshi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, College of Computer Science and Engineering, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1056\/NEJMra1706537","article-title":"Down Syndrome","volume":"382","author":"Bull","year":"2020","journal-title":"N. 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