{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:52Z","timestamp":1786978372116,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T00:00:00Z","timestamp":1525996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008323","name":"Zanjan University of Medical Sciences","doi-asserted-by":"publisher","award":["A\u201012\u2010153\u201011"],"award-info":[{"award-number":["A\u201012\u2010153\u201011"]}],"id":[{"id":"10.13039\/501100008323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>\n                    Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant\u2010derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Artemia salina<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches. Apigenin exhibited significant suppression of parasitemia in a dose\u2010dependent manner; it suppressed\n                    <jats:italic>Plasmodium berghei<\/jats:italic>\n                    growth by 69.74%, 50.3%, and 49.23% at concentrations of 70, 35, and 15\u00a0mg\/kg\/day, respectively. The IC\n                    <jats:sub>50<\/jats:sub>\n                    value for apigenin after 24\u00a0hr exposure to Huh7 cells was 225\u00a0\u03bcg\/ml. Apigenin did not show noticeable toxicity on\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>A.\u00a0salina<\/jats:italic>\n                    <\/jats:styled-content>\n                    and also on the membrane integrity of red blood cells. After 24\u00a0hr exposure of mice to apigenin, alterations were seen in the metabolism of glucocorticoids and mineralocorticoids, bile acid metabolism (alternative pathway), sulfur metabolism, bile acid metabolism, metabolism of estrogens and androgens, cholesterol catabolism, and biosynthesis of cholesterol. These findings indicate that apigenin has potential in vivo antiplasmodial activity against\n                    <jats:italic>P.\u00a0berghei<\/jats:italic>\n                    infected mice with high selectivity against malaria, but it can disrupt some metabolic pathways in mice.\n                  <\/jats:p>","DOI":"10.1002\/ptr.6113","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T03:08:01Z","timestamp":1526008081000},"page":"1795-1802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Apigenin inhibits growth of the\n                    <i>Plasmodium berghei<\/i>\n                    and disrupts some metabolic pathways in mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Mahdi","family":"Amiri","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Mycology Zanjan University of Medical Sciences  Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbasali","family":"Nourian","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Mycology Zanjan University of Medical Sciences  Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Khoshkam","sequence":"additional","affiliation":[{"name":"Chemistry Group, Faculty of Basic Sciences University of Mohaghegh Ardabili  Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0369-2981","authenticated-orcid":false,"given":"Ali","family":"Ramazani","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Research Center Zanjan University of Medical Sciences  Zanjan Iran"},{"name":"Department of Pharmaceutical Biotechnology Zanjan University of Medical Sciences  Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10942912.2016.1207188"},{"issue":"2","key":"e_1_2_8_3_1","first-page":"93","article-title":"Assessment of metabolite alteration induced by \u2212OH functionalized multi\u2010walled carbon nanotubes in mice using NMR\u2010based metabonomics","volume":"8","author":"Baghdadchi Y.","year":"2018","journal-title":"BioImpacts: BI"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5936\/csbj.201301009"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cem.2609"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-017-9395-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00541-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2015.05.001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.08.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1744-7348.1949.tb06408.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004442"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.05.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000893"},{"issue":"4","key":"e_1_2_8_14_1","first-page":"415","article-title":"Antimalarial evaluation of selected medicinal plant extracts used in Iranian traditional medicine","volume":"20","author":"Haddad M. H. F.","year":"2017","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b12-00627"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(90)90335-I"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30048-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5689"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/znc-2002-3-413"},{"issue":"5","key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1016\/S0021-9258(19)50764-5","article-title":"Characterization of human 3 beta\u2010hydroxysteroid dehydrogenase\/delta 5\u2010delta 4\u2010isomerase gene and its expression in mammalian cells","volume":"267","author":"Lachance Y.","year":"1992","journal-title":"The Journal of Biological Chemistry"},{"issue":"1","key":"e_1_2_8_21_1","doi-asserted-by":"crossref","DOI":"10.4314\/ajid.v3i1.55070","article-title":"Antiprotozoal activities of compounds isolated from croton lobatus l","volume":"3","author":"Lagnika L.","year":"2009","journal-title":"Afr J Infect Dis."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-1-26"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.5772\/32517"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2010.01.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-971236"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/74.4.418"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5819"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2015.03.002"},{"issue":"1","key":"e_1_2_8_29_1","first-page":"233","article-title":"Apigenin and cancer chemoprevention: Progress, potential and promise (review)","volume":"30","author":"Patel D.","year":"2007","journal-title":"International Journal of Oncology"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-015-0232-z"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.09.014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082562"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40199-015-0105-x"},{"issue":"3","key":"e_1_2_8_34_1","first-page":"371","article-title":"In vitro antiplasmodial activity and cytotoxic effect of (z)\u20102\u2010benzylidene\u20104, 6\u2010dimethoxybenzofuran\u20103(2h)\u2010one derivatives","volume":"11","author":"Ramazani A.","year":"2016","journal-title":"Iranian Journal of Parasitology"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/10837450.2017.1372781"},{"issue":"3","key":"e_1_2_8_36_1","first-page":"924","article-title":"Evaluation of novel \u03b1\u2010(acyloxy)\u2010\u03b1\u2010(quinolin\u20104\u2010yl) acetamides as antiplasmodial agents","volume":"16","author":"Ramazani A.","year":"2017","journal-title":"Iran J Pharm Res."},{"issue":"1","key":"e_1_2_8_37_1","first-page":"35","article-title":"Phoenix dactylifera L. fruit induces cell proliferation of A2780, A172 and HFFF2 cell lines","volume":"12","author":"Ramazani A.","year":"2016","journal-title":"Iran. Journal of Pharmaceutical Sciences"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8223(02)90314-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-013-3555-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules19033681"},{"key":"e_1_2_8_41_1","volume-title":"A tutorial on principal component analysis","author":"Shlens J","year":"2005"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0089-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1352-1364.2006"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.162686"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.10.011"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0099-6"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2016.1187134"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl923"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.30875\/50d27d62-en"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1258-2_22"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.21.1.381"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4165"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639045.2017.1313857"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.6113","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.6113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T07:02:16Z","timestamp":1694847736000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.6113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,11]]},"references-count":52,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/ptr.6113"],"URL":"https:\/\/doi.org\/10.1002\/ptr.6113","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,11]]},"assertion":[{"value":"2018-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}