{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:00:18Z","timestamp":1781359218924,"version":"3.54.1"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Malaysia Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2020\/SKK06\/MAHSA\/03\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK06\/MAHSA\/03\/1"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.lfs.2025.124017","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:38Z","timestamp":1760163878000},"page":"124017","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["In vitro anti-neovascularization and anti-angiogenic activities of Platycladus orientalis (L.) Franco in human retinal endothelial cells via Raf\/MEK 1\/2 and AKT1\/mTOR signaling"],"prefix":"10.1016","volume":"382","author":[{"given":"Jing Xian","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaik Har","family":"Yong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew Huah","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-7206","authenticated-orcid":false,"given":"Zhi Xiang","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2025.124017_bb0005","article-title":"Association of haemoglobin with decreased prevalence of diabetic retinopathy among Tibetan male patients","volume":"15","author":"Yin","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.lfs.2025.124017_bb0010","doi-asserted-by":"crossref","first-page":"454","DOI":"10.18240\/ijo.2025.03.12","article-title":"Renal dysfunction associated with clinical response to intravitreal conbercept therapy for diabetic macular edema","volume":"18","author":"Wu","year":"2025","journal-title":"Int. J. Ophthalmol."},{"key":"10.1016\/j.lfs.2025.124017_bb0015","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.jdiacomp.2012.05.014","article-title":"Investigation of SLC2A1 26177A\/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy","volume":"26","author":"Ng","year":"2012","journal-title":"J. Diabetes Complications"},{"key":"10.1016\/j.lfs.2025.124017_bb0020","first-page":"1","article-title":"Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives","volume":"10","author":"Lee","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.lfs.2025.124017_bb0025","doi-asserted-by":"crossref","first-page":"116299","DOI":"10.1016\/j.jep.2023.116299","article-title":"The extract of Curcumae longae rhizoma suppresses angiogenesis via VEGF-induced PI3K\/AKT-enos-no pathway","volume":"308","author":"Guo","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.lfs.2025.124017_bb0030","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1517\/14728222.2011.553604","article-title":"The role of RAF-1 kinase in diabetic retinopathy","volume":"15","author":"Mohammad","year":"2023","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.lfs.2025.124017_bb0035","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"Panwar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.lfs.2025.124017_bb0040","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jare.2022.10.005","article-title":"Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation","volume":"50","author":"Qian","year":"2023","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.lfs.2025.124017_bb0045","doi-asserted-by":"crossref","first-page":"115302","DOI":"10.1016\/j.jep.2022.115302","article-title":"Platycladus orientalis seed extract as a potential triple reuptake MAO inhibitor rescue depression phenotype through restoring monoamine neurotransmitters","volume":"295","author":"Yan","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.lfs.2025.124017_bb0050","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1142\/S0192415X14500347","article-title":"Platycladus orientalis leaves: A systemic review on botany, phytochemistry and pharmacology","volume":"42","author":"Shan","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.lfs.2025.124017_bb0055","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.biopha.2018.07.010","article-title":"Non-toxic and non teratogenic extract of Thuja orientalis L. inhibited angiogenesis in zebra fish and suppressed the growth of human lung cancer cell line","volume":"106","author":"Evangeline","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.lfs.2025.124017_bb0060","doi-asserted-by":"crossref","DOI":"10.1002\/cbdv.202200655","article-title":"The efficacy of traditional medicinal plants in modulating the main protease of SARS-CoV-2 and cytokine storm","volume":"19","author":"Choe","year":"2022","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.lfs.2025.124017_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110999","article-title":"Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells","volume":"133","author":"Han","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.lfs.2025.124017_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108293","article-title":"A human retinal microvascular endothelial-pericyte co-culture model to study diabetic retinopathy in vitro","volume":"201","author":"Eyre","year":"2020","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.lfs.2025.124017_bb0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/3034953","article-title":"A critical analysis of the available in vitro and ex vivo methods to study retinal angiogenesis","author":"Moleiro","year":"2017","journal-title":"J. Ophthalmol."},{"key":"10.1016\/j.lfs.2025.124017_bb0080","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1007\/s12010-022-03921-9","article-title":"Comparative analysis of in vitro enzyme inhibitory activities and phytochemicals from Platycladus orientalis (L.) franco via solvent partitioning method","volume":"194","author":"Ho","year":"2022","journal-title":"Appl. Biochem. Biotechnol."},{"key":"10.1016\/j.lfs.2025.124017_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107969","article-title":"In vitro anti-inflammatory activity and molecular docking of Peperomia pellucida (L.) kunth extract via the NF-\u039aB and PPAR-\u03b3 signalling in human retinal pigment epithelial cells","volume":"153","author":"Ho","year":"2024","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.lfs.2025.124017_bb0090","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1038\/srep04659","article-title":"A simple, inexpensive method for preparing cell lysates suitable for downstream reverse transcription quantitative PCR","volume":"4","author":"Shatzkes","year":"2014","journal-title":"Sci. Rep."},{"key":"10.1016\/j.lfs.2025.124017_bb0095","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1039\/C4MT00033A","article-title":"Native SDS-PAGE: High resolution electrophoretic separation of proteins with retention of native properties including bound metal ions","volume":"6","author":"Nowakowski","year":"2014","journal-title":"Metallomics"},{"key":"10.1016\/j.lfs.2025.124017_bb0100","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3390\/bios13020290","article-title":"Microfluidic wound-healing assay for ECM and microenvironment properties on microglia BV2 cells migration","volume":"13","author":"Yazdanpanah Moghadam","year":"2023","journal-title":"Biosensors"},{"key":"10.1016\/j.lfs.2025.124017_bb0105","article-title":"Endothelial cell tube formation assay for the in vitro study of angiogenesis","volume":"91","author":"DeCicco-Skinner","year":"2014","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.lfs.2025.124017_bb0110","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.3390\/ijms21197078","article-title":"Monoterpenes and their derivatives\u2014recent development in biological and medical applications","volume":"21","author":"Zieli\u0144ska-B\u0142ajet","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.lfs.2025.124017_bb0115","doi-asserted-by":"crossref","first-page":"477","DOI":"10.55730\/1300-011X.3019","article-title":"Crude extracts and essential oil of Platycladus orientalis (L.) franco: A source of phenolics with antioxidant and antibacterial potential as assessed through a chemometric approach","volume":"46","author":"Khammassi","year":"2022","journal-title":"Turk. J. Agric. For."},{"key":"10.1016\/j.lfs.2025.124017_bb0120","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.22207\/JPAM.13.2.44","article-title":"Antibacterial activity of ethyl acetate extract of Platycladus orientalis against Staphylococcus saprophyticus","volume":"13","author":"Abdallah","year":"2019","journal-title":"J. Pure Appl. Microbiol."},{"key":"10.1016\/j.lfs.2025.124017_bb0125","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.3390\/ijms24065339","article-title":"Role of Terpenophenolics in modulating inflammation and apoptosis in cardiovascular diseases: A Review","volume":"24","author":"Abdul Ghani","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.lfs.2025.124017_bb0130","doi-asserted-by":"crossref","first-page":"15935","DOI":"10.3390\/ijms232415935","article-title":"Synergistic effects of ginsenoside RB3 and ferruginol in ischemia-induced myocardial infarction","volume":"23","author":"Chen","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.lfs.2025.124017_bb0135","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27196477","article-title":"Chemical composition, antioxidant and antiproliferative activities of Taraxacum officinale essential oil","volume":"27","author":"Kamal","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.lfs.2025.124017_bb0140","doi-asserted-by":"crossref","first-page":"106641","DOI":"10.1016\/j.jff.2024.106641","article-title":"Syzygium cumini fresh juice ameliorated memory impairment in a scopolamine-induced amnesic mouse model through active avoidance paradigm","volume":"124","author":"Malik","year":"2025","journal-title":"J. Funct. Foods"},{"key":"10.1016\/j.lfs.2025.124017_bb0145","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/chromsci\/bmy066","article-title":"Simultaneous determination of quercitrin, Afzelin, amentoflavone, hinokiflavone in rat plasma by UFLC\u2013MS-MS and its application to the pharmacokinetics of Platycladus orientalis leaves extract","volume":"56","author":"Shan","year":"2018","journal-title":"J. Chromatogr. Sci."},{"key":"10.1016\/j.lfs.2025.124017_bb0150","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1002\/fft2.299","article-title":"Tomato and human health: a perspective from post-harvest processing, nutrient bio-accessibility, and pharmacological interaction","volume":"4","author":"Yong","year":"2023","journal-title":"Food Frontiers"},{"key":"10.1016\/j.lfs.2025.124017_bb0155","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jare.2024.01.016","article-title":"The role of endothelial cell\u2013pericyte interactions in vascularization and diseases","volume":"67","author":"Li","year":"2024","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.lfs.2025.124017_bb0160","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41569-022-00770-1","article-title":"Vascular Endothelial Cell Development and diversity","volume":"20","author":"Trimm","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.lfs.2025.124017_bb0165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/ejmp\/2022\/v33i1030491","article-title":"In vitro antiproliferative studies of selected medicinal plants on cancerous and normal cells","volume":"33","author":"Mbugua","year":"2022","journal-title":"European J. Med. Plants"},{"key":"10.1016\/j.lfs.2025.124017_bb0170","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00005-023-00686-9","article-title":"Prolonged exposure to high glucose induces premature senescence through oxidative stress and autophagy in retinal pigment epithelial cells","volume":"71","author":"Chiu","year":"2023","journal-title":"Arch. Immunol. Ther. Exp. (Warsz.)"},{"key":"10.1016\/j.lfs.2025.124017_bb0175","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijcard.2019.12.065","article-title":"Hyperglycemia-induced endothelial dysfunction is alleviated by thioredoxin mimetic peptides through the restoration of VEGFR-2-induced responses and improved cell survival","volume":"308","author":"Hemling","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.lfs.2025.124017_bb0180","doi-asserted-by":"crossref","first-page":"15339","DOI":"10.1038\/s41598-019-51603-0","article-title":"Distinct downstream signaling and the roles of VEGF and PLGF in high glucose-mediated injuries of human retinal endothelial cells in culture","volume":"9","author":"Jiao","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.lfs.2025.124017_bb0185","first-page":"1","article-title":"Molecular bases of VEGFR-2-mediated physiological function and pathological role","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.lfs.2025.124017_bb0190","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.rmed.2019.08.003","article-title":"VEGF and FGF-2: Promising targets for the treatment of respiratory disorders","volume":"156","author":"Laddha","year":"2019","journal-title":"Respir. Med."},{"key":"10.1016\/j.lfs.2025.124017_bb0195","doi-asserted-by":"crossref","DOI":"10.1172\/JCI161366","article-title":"Endothelial VEGFR2-PLC\u03b3 signaling regulates vascular permeability and antitumor immunity through eNOS\/Src","volume":"133","author":"Sj\u00f6berg","year":"2023","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.lfs.2025.124017_bb0200","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s12272-025-01545-1","article-title":"Targeting vascular endothelial growth receptor-2 (VEGFR-2): Structural Biology, functional insights, and therapeutic resistance","volume":"48","author":"Shah","year":"2025","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.lfs.2025.124017_bb0205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41420-023-01717-2","article-title":"Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy","volume":"9","author":"Li","year":"2023","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.lfs.2025.124017_bb0210","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1016\/j.bpj.2021.03.018","article-title":"The structural basis of AKT ph domain interaction with calmodulin","volume":"120","author":"Weako","year":"2021","journal-title":"Biophys. J."},{"key":"10.1016\/j.lfs.2025.124017_bb0215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12938-021-00904-5","article-title":"Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells","volume":"20","author":"Fang","year":"2021","journal-title":"Biomed. Eng. Online"},{"key":"10.1016\/j.lfs.2025.124017_bb0220","doi-asserted-by":"crossref","first-page":"67","DOI":"10.31083\/j.jin.2021.01.242","article-title":"Geniposide protection against A\u03921-42 toxicity correlates with mTOR inhibition and enhancement of autophagy","volume":"20","author":"Liu","year":"2021","journal-title":"J. Integr. Neurosci."},{"key":"10.1016\/j.lfs.2025.124017_bb0225","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1517\/14728222.2011.645805","article-title":"Targeting the MAPK\u2013 RAS\u2013RAF signaling pathway in cancer therapy","volume":"16","author":"Santarpia","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.lfs.2025.124017_bb0230","first-page":"1","article-title":"Endothelial dysfunction in vascular complications of diabetes: A comprehensive review of mechanisms and implications","volume":"15","author":"Yang","year":"2024","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.lfs.2025.124017_bb0235","first-page":"1263","article-title":"Roles of the RAF\/MEK\/ERK pathway in cell growth, malignant transformation and drug resistance, Biochimica et Biophysica Acta (BBA)-Molecular","volume":"1773","author":"McCubrey","year":"2007","journal-title":"Cell Res."},{"key":"10.1016\/j.lfs.2025.124017_bb0240","first-page":"1","article-title":"The role of ERK1\/2 signaling in diabetes: Pathogenic and therapeutic implications","volume":"16","author":"Xu","year":"2025","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.lfs.2025.124017_bb0245","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: From mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.lfs.2025.124017_bb0250","doi-asserted-by":"crossref","first-page":"185","DOI":"10.6061\/clinics\/2013(02)OA11","article-title":"Attenuated levels of pro-inflammatory markers in diabetic retinopathy patients undergoing treatment with antihyperglycemic and antihypertensive drugs","volume":"68","author":"Ng","year":"2013","journal-title":"Clinics"},{"key":"10.1016\/j.lfs.2025.124017_bb0255","doi-asserted-by":"crossref","first-page":"17858","DOI":"10.18632\/oncotarget.24909","article-title":"High levels of circulating endothelial progenitor cells in patients with diabetic retinopathy are positively associated with arhgap22 expression","volume":"9","author":"Huang","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.lfs.2025.124017_bb0260","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3390\/cells8040288","article-title":"Modulation of receptor tyrosine kinase activity through alternative splicing of ligands and receptors in the VEGF-A\/VEGFR Axis","volume":"8","author":"Stevens","year":"2019","journal-title":"Cells"}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320525006538?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320525006538?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:35:57Z","timestamp":1762421757000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320525006538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":52,"alternative-id":["S0024320525006538"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2025.124017","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vitro anti-neovascularization and anti-angiogenic activities of Platycladus orientalis (L.) Franco in human retinal endothelial cells via Raf\/MEK 1\/2 and AKT1\/mTOR signaling","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2025.124017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"124017"}}