{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:30:49Z","timestamp":1782563449580,"version":"3.54.5"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81503444"],"award-info":[{"award-number":["81503444"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2020,3]]},"DOI":"10.1016\/j.biopha.2019.109729","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T23:01:09Z","timestamp":1577401269000},"page":"109729","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":114,"special_numbering":"C","title":["Combination of tanshinone IIA and astragaloside IV attenuate atherosclerotic plaque vulnerability in ApoE(-\/-) mice by activating PI3K\/AKT signaling and suppressing TRL4\/NF-\u03baB signaling"],"prefix":"10.1016","volume":"123","author":[{"given":"Nanding","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Wenjie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7","key":"10.1016\/j.biopha.2019.109729_bib0005","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1253\/circj.CJ-13-0702","article-title":"Cardiovascular disease epidemiology in Asia: an overview","volume":"77","author":"Ohira","year":"2013","journal-title":"Circ. J."},{"key":"10.1016\/j.biopha.2019.109729_bib0010","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3389\/fphys.2014.00455","article-title":"Inflammatory therapeutic targets in coronary atherosclerosis-from molecular biology to clinical application","volume":"5","author":"Linden","year":"2014","journal-title":"Front. Physiol."},{"issue":"24","key":"10.1016\/j.biopha.2019.109729_bib0015","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1056\/NEJMoa035655","article-title":"Intraplaque hemorrhage and progression of coronary atheroma","volume":"349","author":"Kolodgie","year":"2003","journal-title":"N. Engl. J. Med."},{"issue":"23","key":"10.1016\/j.biopha.2019.109729_bib0020","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1161\/hc4701.099488","article-title":"Global burden of cardiovascular diseases: part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies","volume":"104","author":"Yusuf","year":"2001","journal-title":"Circulation"},{"issue":"Suppl","key":"10.1016\/j.biopha.2019.109729_bib0025","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.1016\/0021-9150(95)90081-0","article-title":"Vulnerable and dangerous coronary plaques","volume":"118","author":"Schroeder","year":"1995","journal-title":"Atherosclerosis"},{"issue":"11","key":"10.1016\/j.biopha.2019.109729_bib0030","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.2967\/jnumed.107.038661","article-title":"Role of inflammation in atherosclerosis","volume":"48","author":"Spagnoli","year":"2007","journal-title":"J. Nucl. Med."},{"key":"10.1016\/j.biopha.2019.109729_bib0035","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.phrs.2018.04.013","article-title":"Natural products targeting ER stress pathway for the treatment of cardiovascular diseases","volume":"132","author":"Choy","year":"2018","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.biopha.2019.109729_bib0040","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3389\/fphar.2016.00469","article-title":"Chinese herbal medicine on cardiovascular diseases and the mechanisms of action","volume":"7","author":"Liu","year":"2016","journal-title":"Front. Pharmacol."},{"issue":"5","key":"10.1016\/j.biopha.2019.109729_bib0045","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/aps.2017.193","article-title":"Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics","volume":"39","author":"Li","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"issue":"1","key":"10.1016\/j.biopha.2019.109729_bib0050","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/med.21438","article-title":"Atheroprotective effects and molecular targets of tanshinones derived from herbal medicine Danshen","volume":"38","author":"Fang","year":"2018","journal-title":"Med. Res. Rev."},{"issue":"1","key":"10.1016\/j.biopha.2019.109729_bib0055","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ejphar.2010.07.038","article-title":"Tanshinone IIA attenuates atherosclerosis in ApoE(-\/-) mice through down-regulation of scavenger receptor expression","volume":"650","author":"Tang","year":"2011","journal-title":"Eur. J. Pharmacol."},{"issue":"1-2","key":"10.1016\/j.biopha.2019.109729_bib0060","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.abb.2011.08.006","article-title":"Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in apolipoprotein-E knockout mice fed a high cholesterol diet","volume":"515","author":"Xu","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"issue":"1","key":"10.1016\/j.biopha.2019.109729_bib0065","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.atherosclerosis.2011.06.041","article-title":"Cardiovascular actions and therapeutic potential of tanshinone IIA","volume":"220","author":"Gao","year":"2012","journal-title":"Atherosclerosis"},{"issue":"5","key":"10.1016\/j.biopha.2019.109729_bib0070","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s10753-017-0603-8","article-title":"Tanshinone IIA attenuates atherosclerosis in apolipoprotein e knockout mice infected with Porphyromonas gingivalis","volume":"40","author":"Xuan","year":"2017","journal-title":"Inflammation"},{"issue":"4","key":"10.1016\/j.biopha.2019.109729_bib0075","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1242\/bio.024133","article-title":"Tanshinone IIA suppresses the progression of atherosclerosis by inhibiting the apoptosis of vascular smooth muscle cells and the proliferation and migration of macrophages induced by ox-LDL","volume":"6","author":"Wang","year":"2017","journal-title":"Biol. Open"},{"issue":"6","key":"10.1016\/j.biopha.2019.109729_bib0080","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1159\/000486166","article-title":"Astragaloside IV prevents cardiac remodeling in the apolipoprotein E-deficient mice by regulating cardiac homeostasis and oxidative stress","volume":"44","author":"Li","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.biopha.2019.109729_bib0085","article-title":"Effects of astragaloside IV on the SDF-1\/CXCR4 expression in atherosclerosis of apoE(-\/-) mice induced by hyperlipaemia","volume":"2015","author":"Qin","year":"2015","journal-title":"Evid. Complement. Alternat. Med."},{"issue":"3","key":"10.1016\/j.biopha.2019.109729_bib0090","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.jep.2013.10.017","article-title":"Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4\/NF-small ka, CyrillicB signaling pathway in isoproterenol-induced myocardial hypertrophy","volume":"150","author":"Yang","year":"2013","journal-title":"J. Ethnopharmacol."},{"issue":"3","key":"10.1016\/j.biopha.2019.109729_bib0095","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.ijcard.2014.04.226","article-title":"Effectiveness of combination therapy of atorvastatin and non lipid-modifying tanshinone IIA from Danshen in a mouse model of atherosclerosis","volume":"174","author":"Xu","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.biopha.2019.109729_bib0100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2018.08.014","article-title":"Suppression of TLR4 activation by resveratrol is associated with STAT3 and Akt inhibition in oxidized low-density lipoprotein-activated platelets","volume":"836","author":"Sun","year":"2018","journal-title":"Eur. J. Pharmacol."},{"issue":"10","key":"10.1016\/j.biopha.2019.109729_bib0105","first-page":"588","article-title":"Ginkgolide A inhibits lipopolysaccharide-induced inflammatory response in human coronary artery endothelial cells via downregulation of TLR4-NF-kappaB signaling through PI3K\/Akt pathway","volume":"71","author":"Zhaocheng","year":"2016","journal-title":"Pharmazie"},{"issue":"12","key":"10.1016\/j.biopha.2019.109729_bib0110","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1161\/01.ATV.20.12.2587","article-title":"Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse","volume":"20","author":"Rosenfeld","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"4","key":"10.1016\/j.biopha.2019.109729_bib0115","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/neu.480170404","article-title":"Effects of octopamine on miniature excitatory junction potentials from developing and adult moth muscle","volume":"17","author":"Klaassen","year":"1986","journal-title":"J. Neurobiol."},{"issue":"6","key":"10.1016\/j.biopha.2019.109729_bib0120","doi-asserted-by":"crossref","first-page":"4983","DOI":"10.3892\/mmr.2016.5916","article-title":"Tanshinone II A stabilizes vulnerable plaques by suppressing RAGE signaling and NF-kappaB activation in apolipoprotein-E-deficient mice","volume":"14","author":"Zhao","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.biopha.2019.109729_bib0125","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.cca.2013.06.006","article-title":"Foam cells in atherosclerosis","volume":"424","author":"Yu","year":"2013","journal-title":"Clin. Chim. Acta"},{"issue":"2","key":"10.1016\/j.biopha.2019.109729_bib0130","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1194\/jlr.M040394","article-title":"Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of heme oxygenase-1","volume":"55","author":"Liu","year":"2014","journal-title":"J. Lipid Res."},{"issue":"5","key":"10.1016\/j.biopha.2019.109729_bib0135","doi-asserted-by":"crossref","first-page":"422","DOI":"10.2174\/1389201020666190404125213","article-title":"Tanshinone IIA promotes macrophage cholesterol efflux and attenuates atherosclerosis of apoE-\/- mice by Omentin-1\/ABCA1 pathway","volume":"20","author":"Tan","year":"2019","journal-title":"Curr. Pharm. Biotechnol."},{"issue":"10","key":"10.1016\/j.biopha.2019.109729_bib0140","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/mnfr.201100344","article-title":"Blueberries reduce pro-inflammatory cytokine TNF-alpha and IL-6 production in mouse macrophages by inhibiting NF-kappaB activation and the MAPK pathway","volume":"55","author":"Xie","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"issue":"2","key":"10.1016\/j.biopha.2019.109729_bib0145","doi-asserted-by":"crossref","first-page":"H306","DOI":"10.1152\/ajpheart.01306.2010","article-title":"Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice","volume":"301","author":"Lee","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"20","key":"10.1016\/j.biopha.2019.109729_bib0150","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1021\/acs.jafc.9b00540","article-title":"Arginyl-fructosyl-glucose, a major maillard reaction product of red ginseng, attenuates cisplatin-induced acute kidney injury by regulating nuclear factor kappaB and phosphatidylinositol 3-Kinase\/Protein kinase B signaling pathways","volume":"67","author":"Li","year":"2019","journal-title":"J. Agric. Food Chem."},{"issue":"2","key":"10.1016\/j.biopha.2019.109729_bib0155","first-page":"92","article-title":"Effects of herbal-cake-separated moxibustion on blood lipid protein levels and expression of toll-like receptor and nuclear factor genes in atherosclerotic plaques in hyperglycemia rabbits","volume":"43","author":"Zheng","year":"2018","journal-title":"Zhen Ci Yan Jiu"},{"issue":"5","key":"10.1016\/j.biopha.2019.109729_bib0160","doi-asserted-by":"crossref","DOI":"10.3390\/molecules23051101","article-title":"Ursolic acid attenuates atherosclerosis in ApoE(-\/-) mice: role of LOX-1 mediated by ROS\/NF-kappaB pathway","volume":"23","author":"Li","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.biopha.2019.109729_bib0165","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/274314","article-title":"Astragaloside IV inhibits NF- kappa B activation and inflammatory gene expression in LPS-treated mice","volume":"2015","author":"Zhang","year":"2015","journal-title":"Mediators Inflamm."},{"key":"10.1016\/j.biopha.2019.109729_bib0170","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/928315","article-title":"Matrix metalloproteinases: inflammatory regulators of cell behaviors in vascular formation and remodeling","volume":"2013","author":"Chen","year":"2013","journal-title":"Mediators Inflamm."},{"issue":"3","key":"10.1016\/j.biopha.2019.109729_bib0175","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s11307-011-0502-6","article-title":"Multispectral optoacoustic tomography of matrix metalloproteinase activity in vulnerable human carotid plaques","volume":"14","author":"Razansky","year":"2012","journal-title":"Mol. Imaging Biol."},{"issue":"11","key":"10.1016\/j.biopha.2019.109729_bib0180","doi-asserted-by":"crossref","first-page":"998","DOI":"10.5551\/jat.8870","article-title":"The antioxidant N-acetylcysteine promotes atherosclerotic plaque stabilization through suppression of RAGE, MMPs and NF-kappaB in ApoE-deficient mice","volume":"18","author":"Lu","year":"2011","journal-title":"J. Atheroscler. Thromb."},{"issue":"1","key":"10.1016\/j.biopha.2019.109729_bib0185","first-page":"57","article-title":"Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque","volume":"15","author":"Chen","year":"2005","journal-title":"Int. J. Mol. Med."},{"issue":"17\u201318","key":"10.1016\/j.biopha.2019.109729_bib0190","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.lfs.2007.08.043","article-title":"Tanshinone IIA inhibits atherosclerotic plaque formation by down-regulating MMP-2 and MMP-9 expression in rabbits fed a high-fat diet","volume":"81","author":"Fang","year":"2007","journal-title":"Life Sci."},{"issue":"2","key":"10.1016\/j.biopha.2019.109729_bib0195","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jep.2007.09.025","article-title":"Tanshinone IIA downregulates the CD40 expression and decreases MMP-2 activity on atherosclerosis induced by high fatty diet in rabbit","volume":"115","author":"Fang","year":"2008","journal-title":"J. Ethnopharmacol."},{"issue":"31","key":"10.1016\/j.biopha.2019.109729_bib0200","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1200\/JCO.2014.59.0018","article-title":"Inhibition of the PI3K\/AKT\/mTOR pathway in solid tumors","volume":"34","author":"LoRusso","year":"2016","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.biopha.2019.109729_bib0205","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3892\/ijmm.2014.1981","article-title":"PI3K\/AKT\/PTEN pathway as a target for Crohn\u2019s disease therapy (review)","volume":"35","author":"Tokuhira","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.biopha.2019.109729_bib0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109117","article-title":"MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN\/PI3K\/AKT pathway","volume":"117","author":"Zheng","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.biopha.2019.109729_bib0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109099","article-title":"15-Epi-lipoxin A4 inhibits TNF-alpha-induced tissue factor expression via the PI3K\/AKT\/ NF-kappaB axis in human umbilical vein endothelial cells","volume":"117","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"issue":"3","key":"10.1016\/j.biopha.2019.109729_bib0220","first-page":"1436","article-title":"Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart","volume":"42","author":"Liu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.biopha.2019.109729_bib0225","article-title":"Lunasin attenuates oxidant-induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE(-\/-) mice by up-regulating heme oxygenase-1 via PI3K\/Akt\/Nrf2\/ARE pathway","author":"Gu","year":"2019","journal-title":"FASEB J."}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S075333221935351X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S075333221935351X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:51:27Z","timestamp":1760097087000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S075333221935351X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":45,"alternative-id":["S075333221935351X"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2019.109729","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Combination of tanshinone IIA and astragaloside IV attenuate atherosclerotic plaque vulnerability in ApoE(-\/-) mice by activating PI3K\/AKT signaling and suppressing TRL4\/NF-\u03baB signaling","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2019.109729","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"109729"}}