{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:25:02Z","timestamp":1792632302876,"version":"4.5.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["[ZK[2021]YB473]"],"award-info":[{"award-number":["[ZK[2021]YB473]"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Salidroside (SAL), the main component of\n                      <jats:italic>Rhodiola rosea<\/jats:italic>\n                      extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0305343","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T13:40:13Z","timestamp":1720186813000},"page":"e0305343","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Network pharmacology and molecular-docking-based strategy to explore the potential mechanism of salidroside-inhibited oxidative stress in retinal ganglion cell"],"prefix":"10.1371","volume":"19","author":[{"given":"Peng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangping","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-8957","authenticated-orcid":true,"given":"Fang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"issue":"3","key":"pone.0305343.ref001","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/15321819.2020.1726774","article-title":"Biomarkers of inflammation and oxidative stress in ophthalmic disorders","volume":"41","author":"A Ahmad","year":"2020","journal-title":"J Immunoassay Immunochem"},{"issue":"3","key":"pone.0305343.ref002","article-title":"Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress","volume":"6","author":"F Ahmadinejad","year":"2017","journal-title":"Antioxidants (Basel)"},{"key":"pone.0305343.ref003","doi-asserted-by":"crossref","first-page":"3164734","DOI":"10.1155\/2016\/3164734","article-title":"The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults","volume":"2016","author":"M Nita","year":"2016","journal-title":"Oxid Med Cell Longev"},{"issue":"3","key":"pone.0305343.ref004","doi-asserted-by":"crossref","first-page":"129832","DOI":"10.1016\/j.bbagen.2020.129832","article-title":"Molecular imaging for mitochondrial metabolism and oxidative stress in mitochondrial diseases and neurodegenerative disorders","volume":"1865","author":"M Ikawa","year":"2021","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"6","key":"pone.0305343.ref005","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.exer.2010.03.008","article-title":"Mitochondria: Their role in ganglion cell death and survival in primary open angle glaucoma","volume":"90","author":"NN Osborne","year":"2010","journal-title":"Exp Eye Res"},{"issue":"5","key":"pone.0305343.ref006","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.preteyeres.2006.07.003","article-title":"Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences","volume":"25","author":"G. Tezel","year":"2006","journal-title":"Prog Retin Eye Res"},{"issue":"9","key":"pone.0305343.ref007","article-title":"PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction","volume":"9","author":"M Ikawa","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"pone.0305343.ref008","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.exer.2014.04.015","article-title":"Endoplasmic reticulum stress and the unfolded protein responses in retinal degeneration","volume":"125","author":"SX Zhang","year":"2014","journal-title":"Exp Eye Res"},{"key":"pone.0305343.ref009","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1750-1326-8-32","article-title":"Dominant optic atrophy, OPA1, and mitochondrial quality control: understanding mitochondrial network dynamics","volume":"8","author":"MV Alavi","year":"2013","journal-title":"Mol Neurodegener"},{"issue":"1","key":"pone.0305343.ref010","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/13510002.2019.1658377","article-title":"Salidroside inhibits MAPK, NF-\u03baB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation","volume":"24","author":"F Xu","year":"2019","journal-title":"Redox Rep"},{"key":"pone.0305343.ref011","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","article-title":"Reperfusion injury and reactive oxygen species: The evolution of a concept","volume":"6","author":"DN Granger","year":"2015","journal-title":"Redox Biol"},{"key":"pone.0305343.ref012","doi-asserted-by":"crossref","first-page":"172797","DOI":"10.1016\/j.ejphar.2019.172797","article-title":"Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK\/NF-\u03baB\/NLRP3 signaling pathway in AGEs-induced HUVECs","volume":"867","author":"R Hu","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"pone.0305343.ref013","doi-asserted-by":"crossref","first-page":"723922","DOI":"10.3389\/fphar.2021.723922","article-title":"Salidroside Ameliorated Intermittent Hypoxia-Aggravated Endothelial Barrier Disruption and Atherosclerosis via the cAMP\/PKA\/RhoA Signaling Pathway","volume":"12","author":"L Li","year":"2021","journal-title":"Front Pharmacol"},{"issue":"1","key":"pone.0305343.ref014","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12906-019-2526-4","article-title":"Salidroside protects against ox-LDL-induced endothelial injury by enhancing autophagy mediated by SIRT1-FoxO1 pathway","volume":"19","author":"Z Zhu","year":"2019","journal-title":"BMC Complement Altern Med"},{"key":"pone.0305343.ref015","first-page":"3549704","article-title":"Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy","volume":"2020","author":"C Gu","year":"2020","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0305343.ref016","doi-asserted-by":"crossref","first-page":"154020","DOI":"10.1016\/j.phymed.2022.154020","article-title":"Salidroside protects against osteoporosis in ovariectomized rats by inhibiting oxidative stress and promoting osteogenesis via Nrf2 activation","volume":"99","author":"YF Wang","year":"2022","journal-title":"Phytomedicine"},{"key":"pone.0305343.ref017","doi-asserted-by":"crossref","first-page":"152905","DOI":"10.1016\/j.tox.2021.152905","article-title":"Salidroside alleviates liver inflammation in furan-induced mice by regulating oxidative stress and endoplasmic reticulum stress","volume":"461","author":"Y Yuan","year":"2021","journal-title":"Toxicology"},{"issue":"6","key":"pone.0305343.ref018","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1002\/hep.32066","article-title":"Salidroside Activates the AMP-Activated Protein Kinase Pathway to Suppress Nonalcoholic Steatohepatitis in Mice","volume":"74","author":"M Hu","year":"2021","journal-title":"Hepatology"},{"issue":"9","key":"pone.0305343.ref019","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1002\/fsn3.2459","article-title":"Protective effect of Salidroside on hypoxia-related liver oxidative stress and inflammation via Nrf2 and JAK2\/STAT3 signaling pathways","volume":"9","author":"Y Xiong","year":"2021","journal-title":"Food Sci Nutr"},{"issue":"1","key":"pone.0305343.ref020","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s10753-019-01121-y","article-title":"Salidroside Restores an Anti-inflammatory Endothelial Phenotype by Selectively Inhibiting Endothelial Complement After Oxidative Stress","volume":"43","author":"Y Wang","year":"2020","journal-title":"Inflammation"},{"key":"pone.0305343.ref021","doi-asserted-by":"crossref","first-page":"861452","DOI":"10.3389\/fendo.2022.861452","article-title":"Long-Term Oral Administration of Salidroside Alleviates Diabetic Retinopathy in db\/db Mice","volume":"13","author":"F Yao","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0305343.ref022","doi-asserted-by":"crossref","first-page":"174617","DOI":"10.1016\/j.ejphar.2021.174617","article-title":"Salidroside attenuates CoCl(2)-simulated hypoxia injury in PC12 cells partly by mitochondrial protection","volume":"912","author":"Y Tang","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"pone.0305343.ref023","doi-asserted-by":"crossref","first-page":"172591","DOI":"10.1016\/j.ejphar.2019.172591","article-title":"Salidroside attenuates dextran sulfate sodium-induced colitis in mice via SIRT1\/FoxOs signaling pathway","volume":"861","author":"H Li","year":"2019","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"pone.0305343.ref024","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1530\/JOE-19-0393","article-title":"Anti-insulin resistance effects of salidroside through mitochondrial quality control","volume":"244","author":"B You","year":"2020","journal-title":"J Endocrinol"},{"issue":"6","key":"pone.0305343.ref025","first-page":"2279","article-title":"Salidroside attenuates oxidized low\u2011density lipoprotein\u2011induced endothelial cell injury via promotion of the AMPK\/SIRT1 pathway","volume":"43","author":"D Zhao","year":"2019","journal-title":"Int J Mol Med"},{"issue":"1","key":"pone.0305343.ref026","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13578-022-00918-z","article-title":"Salidroside reduces neuropathology in Alzheimer\u2019s disease models by targeting NRF2\/SIRT3 pathway","volume":"12","author":"Y Yao","year":"2022","journal-title":"Cell Biosci"},{"key":"pone.0305343.ref027","doi-asserted-by":"crossref","first-page":"109094","DOI":"10.1016\/j.abb.2021.109094","article-title":"Salidroside alleviates oxidative stress and apoptosis via AMPK\/Nrf2 pathway in DHT-induced human granulosa cell line KGN","volume":"715","author":"R Ji","year":"2022","journal-title":"Arch Biochem Biophys"},{"issue":"8","key":"pone.0305343.ref028","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1007\/s11011-022-01061-x","article-title":"Salidroside inhibited cerebral ischemia\/reperfusion-induced oxidative stress and apoptosis via Nrf2\/Trx1 signaling pathway","volume":"37","author":"F Li","year":"2022","journal-title":"Metab Brain Dis"},{"issue":"1","key":"pone.0305343.ref029","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13020-022-00634-3","article-title":"Salidroside attenuates neuronal ferroptosis by activating the Nrf2\/HO1 signaling pathway in A\u03b2(1\u201342)-induced Alzheimer\u2019s disease mice and glutamate-injured HT22 cells","volume":"17","author":"S Yang","year":"2022","journal-title":"Chin Med"},{"key":"pone.0305343.ref030","doi-asserted-by":"crossref","first-page":"109975","DOI":"10.1016\/j.intimp.2023.109975","article-title":"Salidroside attenuates lipopolysaccharide-induced neuroinflammation and cognitive impairment in septic encephalopathy mice","volume":"117","author":"L Xiao","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"pone.0305343.ref031","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.vph.2015.07.004","article-title":"Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK\/PI3K\/Akt\/eNOS pathway","volume":"72","author":"SS Xing","year":"2015","journal-title":"Vascul Pharmacol"},{"issue":"7","key":"pone.0305343.ref032","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1142\/S0192415X19500782","article-title":"Role of EGFR\/ErbB2 and PI(3)K\/AKT\/e-NOS in Lycium barbarum polysaccharides Ameliorating Endothelial Dysfunction Induced by Oxidative Stress","volume":"47","author":"W Zhang","year":"2019","journal-title":"Am J Chin Med"},{"issue":"17","key":"pone.0305343.ref033","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231710188","article-title":"Leonurine Reduces Oxidative Stress and Provides Neuroprotection against Ischemic Injury via Modulating Oxidative and NO\/NOS Pathway","volume":"23","author":"Z Deng","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0305343.ref034","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.freeradbiomed.2019.12.012","article-title":"Rutaecarpine inhibits KEAP1-NRF2 interaction to activate NRF2 and ameliorate dextran sulfate sodium-induced colitis","volume":"148","author":"Y Zhang","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"pone.0305343.ref035","first-page":"9626703","article-title":"Pretreatment with Panaxatriol Saponin Attenuates Mitochondrial Apoptosis and Oxidative Stress to Facilitate Treatment of Myocardial Ischemia-Reperfusion Injury via the Regulation of Keap1\/Nrf2 Activity","volume":"2022","author":"H Yao","year":"2022","journal-title":"Oxid Med Cell Longev"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T13:40:34Z","timestamp":1720186834000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305343"}},"subtitle":[],"editor":[{"given":"Yash","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0305343","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]}}}