{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:50:52Z","timestamp":1781830252792,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atherosclerosis (AS) is a major cause of cardiovascular diseases, with OX\u2010LDL\u2010induced VSMC dysfunction being a critical pathogenic driver of AS development. Saikosaponin D (SSD), a bioactive compound, shows therapeutic potential, but its mechanism in AS is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An atherosclerotic cell model was established by treating hVSMCs with OX\u2010LDL. Intracellular ROS was detected via a fluorescent probe, MDA content and SOD activity via biochemical kits. Inflammatory cytokines (IL\u20106, IL\u20108 and TNF\u2010\u03b1) were quantified by ELISA. Lipid parameters (TG, LDL and HDL) were analysed biochemically, and intracellular lipid accumulation was assessed via Oil Red O staining. Autophagy (LC3B and p62) and senescence\u2010related (p16 and p21) protein expression was detected by WB, with cellular senescence further assessed via SA\u2010\u03b2\u2010gal staining. SSD's potential targets were predicted via bioinformatics (CTD, SwissTargetPrediction and GeneCards). SSD\u2010EPHB2 interaction was predicted by AutoDock Vina docking (visualised by PyMOL), and its stability was evaluated by using iMODS\u2010based NMA. EPHB2's functional role was confirmed via its overexpression in hVSMCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SSD significantly attenuated OX\u2010LDL\u2010induced oxidative stress, inflammation, lipid accumulation, autophagic flux impairment and cellular senescence in hVSMCs. Bioinformatics analysis pinpointed EPHB2 as a hub gene. Molecular studies confirmed that SSD directly binds to EPHB2 and downregulates its expression. Crucially, overexpressing EPHB2 abolished all the protective effects of SSD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SSD alleviates OX\u2010LDL\u2010induced hVSMC dysfunction by inhibiting EPHB2, highlighting the SSD\u2010EPHB2 pathway as a potential therapeutic target for AS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70131","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:54:01Z","timestamp":1781672041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Saikosaponin D Alleviates Atherosclerosis by Regulating Autophagy and Senescence of\n                    <scp>VSMCs<\/scp>\n                    via Inhibiting\n                    <scp>EPHB2<\/scp>"],"prefix":"10.1111","volume":"53","author":[{"given":"Meihua","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangwei","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5595-2719","authenticated-orcid":false,"given":"Xinri","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangxi University of Chinese Medicine  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Emergency Guangxi International Zhuang Medicine Hospital  Nanning City Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom8030080"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13202"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-018-0032-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8070218"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02558-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-021-10000-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S447379"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122560"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgad052"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2021.3054"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111409"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001206"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.120042"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-021-00189-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.2A0320-283RR"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03392-y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12444"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070339"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-025-10054-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-021-01594-y"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy007"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3018190"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.09.033"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.106031"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180820666230719121428"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2021.106731"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2023.69.3.10"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119833"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77484"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70131","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1440-1681.70131","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:53:55Z","timestamp":1781826835000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.70131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/1440-1681.70131"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.70131","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70131"}}