{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:02:37Z","timestamp":1790596957496,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009377","name":"Scientific Research Project of Hunan Provincial Department of Education","doi-asserted-by":"publisher","award":["22A0589"],"award-info":[{"award-number":["22A0589"]}],"id":[{"id":"10.13039\/100009377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016317","name":"Provincial Special Project for Construction of Innovation Demonstration Area at Chenzhou City under National Sustainable Development Plan","doi-asserted-by":"publisher","award":["2023sfq04"],"award-info":[{"award-number":["2023sfq04"]}],"id":[{"id":"10.13039\/501100016317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"Hunan Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2023JJ50064"],"award-info":[{"award-number":["2023JJ50064"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Endothelial cell senescence is a key contributor to vascular ageing and cardiovascular diseases. Asiaticoside, a pentacyclic triterpenoid saponin from Centella asiatica, exhibits anti-inflammatory and antioxidant activities, yet its potential to modulate endothelial senescence remains unexplored. Herein, we report the molecular docking-guided discovery of asiaticoside as a multi-target modulator of the SIRT1\/HMGB1\/p53\u2013p21 senescence regulatory axis. Asiaticoside was isolated via a green acid-hydrolysis strategy using dilute HCl as the extraction solvent, followed by polyamide enrichment and C18 reversed-phase purification (purity &gt; 98%). Molecular docking revealed that asiaticoside binds favourably to SIRT1 (\u22128.1 kcal mol\u22121), the HMGB1\u2013DNA complex (\u221210.7 kcal mol\u22121), and several senescence-associated secretory phenotype (SASP)-related inflammatory cytokines. In H2O2-induced senescent human umbilical vein endothelial cells (HUVECs), asiaticoside at 100 \u03bcM significantly reduced senescence-associated \u03b2-galactosidase activity and alleviated G0\/G1 cell cycle arrest without cytotoxicity. Mechanistically, asiaticoside restored SIRT1 expression, suppressed the secretion of IL-1\u03b2, IL-6, IL-8, TNF-\u03b1, and HMGB1, downregulated p21 at both mRNA and protein levels, reduced p53 protein expression, and suppressed p16 mRNA expression. These findings demonstrate that asiaticoside attenuates endothelial senescence and SASP-driven inflammation, an effect associated with restoration of SIRT1 expression and suppression of the HMGB1\/p53\u2013p21 pathway.<\/jats:p>","DOI":"10.3390\/molecules31193451","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Green Extraction and Molecular Docking-Guided Discovery of Asiaticoside as a Multi-Target Modulator of the SIRT1\/HMGB1\/p53-p21 Axis in H2O2-Induced Senescent Endothelial Cells"],"prefix":"10.3390","volume":"31","author":[{"given":"Wenkai","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9918-3114","authenticated-orcid":false,"given":"Jianhua","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-1812","authenticated-orcid":false,"given":"Fei","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Industrial Technology, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xiangnan University, Chenzhou 423000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.arr.2018.09.004","article-title":"Significance of urinary 11-dehydro-thromboxane B2 in age-related diseases: Focus on atherothrombosis","volume":"48","author":"Simeone","year":"2018","journal-title":"Ageing Res. 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