{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T14:02:16Z","timestamp":1778594536986,"version":"3.51.4"},"reference-count":42,"publisher":"Pharmaceutical Society of Japan","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2020,6,1]]},"DOI":"10.1248\/bpb.b19-01084","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T22:04:34Z","timestamp":1590962674000},"page":"968-975","source":"Crossref","is-referenced-by-count":22,"title":["Potential Mechanisms Underlying the Hepatic\u2013Protective Effects of Danshensu on Iron Overload Mice"],"prefix":"10.1248","volume":"43","author":[{"given":"Yuanyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaohua","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingran","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hebei University of Chinese Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hebei University of Chinese Medicine"},{"name":"Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Anderson ER, Shah YM. Iron homeostasis in the liver. <i>Compr. Physiol.<\/i>, <b>3<\/b>, 315\u2013330 (2013).","DOI":"10.1002\/cphy.c120016"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Gao Y, Wang N, Zhang Y, Ma Z, Guan P, Ma J, Zhang Y, Zhang X, Wang J, Zhang J, Chu L. Mechanism of protective effects of Danshen against iron overload-induced injury in mice. <i>J. Ethnopharmacol.<\/i>, <b>145<\/b>, 254\u2013260 (2013).","DOI":"10.1016\/j.jep.2012.10.060"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Zhang Y, Zhang Y, Xie Y, Gao Y, Ma J, Yuan J, Li J, Wang J, Li L, Zhang J, Chu L. Multitargeted inhibition of hepatic fibrosis in chronic iron-overloaded mice by <i>Salvia miltiorrhiza<\/i>. <i>J. Ethnopharmacol.<\/i>, <b>148<\/b>, 671\u2013681 (2013).","DOI":"10.1016\/j.jep.2013.05.028"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Corradini E, Pietrangelo A. Iron and steatohepatitis. <i>J. Gastroenterol. Hepatol.<\/i>, <b>27<\/b> (Suppl. 2), 42\u201346 (2012).","DOI":"10.1111\/j.1440-1746.2011.07014.x"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Aigner E, Weiss G, Datz C. Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver. <i>World J. Hepatol.<\/i>, <b>7<\/b>, 177\u2013188 (2015).","DOI":"10.4254\/wjh.v7.i2.177"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Georgopoulou U, Dimitriadis A, Foka P, Karamichali E, Mamalaki A. Hepcidin and the iron enigma in HCV infection. <i>Virulence<\/i>, <b>5<\/b>, 465\u2013476 (2014).","DOI":"10.4161\/viru.28508"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Milic S, Mikolasevic I, Orlic L, Devcic E, Starcevic-Cizmarevic N, Stimac D, Kapovic M, Ristic S. The role of iron and iron overload in chronic liver disease. <i>Med. Sci. Monit.<\/i>, <b>22<\/b>, 2144\u20132151 (2016).","DOI":"10.12659\/MSM.896494"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Graham RM, Chua AC, Herbison CE, Olynyk JK, Trinder D. Liver iron transport. <i>World J. Gastroenterol.<\/i>, <b>13<\/b>, 4725\u20134736 (2007).","DOI":"10.3748\/wjg.v13.i35.4725"},{"key":"9","unstructured":"9) Ponka P, Beaumont C, Richardson DR. Function and regulation of transferrin and ferritin. <i>Semin. Hematol.<\/i>, <b>35<\/b>, 35\u201354 (1998)."},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. Cloning and characterization of a mammalian proton-coupled metal\u2013ion transporter. <i>Nature<\/i>, <b>388<\/b>, 482\u2013488 (1997).","DOI":"10.1038\/41343"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Trinder D, Oates PS, Thomas C, Sadleir J, Morgan EH. Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload. <i>Gut<\/i>, <b>46<\/b>, 270\u2013276 (2000).","DOI":"10.1136\/gut.46.2.270"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Oudit GY, Sun H, Trivieri MG, Koch SE, Dawood F, Ackerley C, Yazdanpanah M, Wilson GJ, Schwartz A, Liu PP, Backx PH. L-type Ca<sup>2+<\/sup> channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. <i>Nat. Med.<\/i>, <b>9<\/b>, 1187\u20131194 (2003).","DOI":"10.1038\/nm920"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Li M, He HP, Gong HQ, Zhang J, Ma WJ, Zhou H, Cao DS, Wang N, Zhang TC. NFATc4 and myocardin synergistically up-regulate the expression of LTCC alpha1C in ET-1-induced cardiomyocyte hypertrophy. <i>Life Sci.<\/i>, <b>155<\/b>, 11\u201320 (2016).","DOI":"10.1016\/j.lfs.2016.05.007"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Zhang JP, Zhang YY, Zhang Y, Gao YG, Ma JJ, Wang N, Wang JY, Xie Y, Zhang FH, Chu L. <i>Salvia miltiorrhiza<\/i> (Danshen) injection ameliorates iron overload-induced cardiac damage in mice. <i>Planta Med.<\/i>, <b>79<\/b>, 744\u2013752 (2013).","DOI":"10.1055\/s-0032-1328588"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Guan S, Ma J, Zhang Y, Gao Y, Zhang Y, Zhang X, Wang N, Xie Y, Wang J, Zhang J, Chu L. Danshen (<i>Salvia miltiorrhiza<\/i>) injection suppresses kidney injury induced by iron overload in mice. <i>PLOS ONE<\/i>, <b>8<\/b>, e74318 (2013).","DOI":"10.1371\/journal.pone.0074318"},{"key":"16","unstructured":"16) Su CY, Ming QL, Rahman K, Han T, Qin LP. <i>Salvia miltiorrhiza<\/i>: Traditional medicinal uses, chemistry, and pharmacology. <i>Chin. J. Nat. Med.<\/i>, <b>13<\/b>, 163\u2013182 (2015)."},{"key":"17","unstructured":"17) Cheng TO. Danshen: a versatile Chinese herbal drug for the treatment of coronary heart disease. <i>Int. J. Cardiol.<\/i>, <b>113<\/b>, 437\u2013438 (2006)."},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Lam FF, Yeung JH, Cheung JH, Or PM. Pharmacological evidence for calcium channel inhibition by Danshen (<i>Salvia miltiorrhiza<\/i>) on rat isolated femoral artery. <i>J. Cardiovasc. Pharmacol.<\/i>, <b>47<\/b>, 139\u2013145 (2006).","DOI":"10.1097\/01.fjc.0000197540.12685.ce"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Zhang J, Zhang Q, Liu G, Zhang N. Therapeutic potentials and mechanisms of the Chinese traditional medicine Danshensu. <i>Eur. J. Pharmacol.<\/i>, <b>864<\/b>, 172710 (2019).","DOI":"10.1016\/j.ejphar.2019.172710"},{"key":"20","unstructured":"20) Yu J, Wang L, Akinyi M, Li Y, Duan Z, Zhu Y, Fan G. Danshensu protects isolated heart against ischemia reperfusion injury through activation of Akt\/ERK1\/2\/Nrf2 signaling. <i>Int. J. Clin. Exp. Med.<\/i>, <b>8<\/b>, 14793\u201314804 (2015)."},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Cao G, Zhu R, Jiang T, Tang D, Kwan HY, Su T. Danshensu, a novel indoleamine 2,3-dioxygenase1 inhibitor, exerts anti-hepatic fibrosis effects <i>via<\/i> inhibition of JAK2-STAT3 signaling. <i>Phytomedicine<\/i>, <b>63<\/b>, 153055 (2019).","DOI":"10.1016\/j.phymed.2019.153055"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Qu W, Huang H, Li K, Qin C. Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats. <i>Pathol. Biol.<\/i>, <b>62<\/b>, 348\u2013353 (2014).","DOI":"10.1016\/j.patbio.2014.07.008"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Ren R, Wang T, Jiang N, Liu T, Du Y, Li C, Zhang L, Fu F. Protective effects of Danshensu on liver injury induced by omethoate in rats. <i>Toxicol. Mech. Methods<\/i>, <b>20<\/b>, 510\u2013514 (2010).","DOI":"10.3109\/15376516.2010.514963"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Zhang Y, Zhao X, Chang Y, Zhang Y, Chu X, Zhang X, Liu Z, Guo H, Wang N, Gao Y, Zhang J, Chu L. Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis. <i>Toxicol. Appl. Pharmacol.<\/i>, <b>301<\/b>, 50\u201360 (2016).","DOI":"10.1016\/j.taap.2016.04.008"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Zhang JL, Cui M, He Y, Yu HL, Guo DA. Chemical fingerprint and metabolic fingerprint analysis of Danshen injection by HPLC-UV and HPLC-MS methods. <i>J. Pharm. Biomed. Anal.<\/i>, <b>36<\/b>, 1029\u20131035 (2005).","DOI":"10.1016\/j.jpba.2004.09.009"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Peng WB, Zeng QH, Li DP, Ding TM, Tan JL, Ding XP. Multiple on-line HPLC coupled with biochemical detection methods to evaluate bioactive compounds in Danshen injection. <i>Biomed. Chromatogr.<\/i>, <b>30<\/b>, 1854\u20131860 (2016).","DOI":"10.1002\/bmc.3772"},{"key":"27","unstructured":"27) Wang C, Zhao R, Li B, Gu LY, Gou H. An <i>in vivo<\/i> and <i>in vitro<\/i> study: High-dosage Danshen injection induces peripheral vascular endothelial cells injury. <i>Hum. Exp. Toxicol.<\/i>, <b>35<\/b>, 404\u2013417 (2016)."},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Lin Y, Wang C, Hou Y, Sun W, Che D, Yang L, Zhang T, Sun M, He H, He L. Simultaneous identification of three pseudoallergic components in Danshen injection by using high-expression Mas-related G protein coupled receptor X2 cell membrane chromatography coupled online to HPLC-ESI-MS\/MS. <i>J. Sep. Sci.<\/i>, <b>41<\/b>, 2488\u20132497 (2018).","DOI":"10.1002\/jssc.201701275"},{"key":"29","unstructured":"29) Hultcrantz R, Hogberg J, Glaumann H. Studies on the rat liver following iron overload: an analysis of iron and lysosomal enzymes in isolated parenchymal and non-parenchymal cells. <i>Virchows Arch. B Cell Pathol. Incl. Mol. Pathol.<\/i>, <b>43<\/b>, 67\u201374 (1983)."},{"key":"30","unstructured":"30) Knolle P, Lohr H, Treichel U, Dienes HP, Lohse A, Schlaack J, Gerken G. Parenchymal and nonparenchymal liver cells and their interaction in the local immune response. <i>Z. Gastroenterol.<\/i>, <b>33<\/b>, 613\u2013620 (1995)."},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Xing XK, Wu HY, Feng HG, Yuan ZQ. Immune function of nonparenchymal liver cells. <i>Genet. Mol. Res.<\/i>, <b>15<\/b>, gmr.15018524 (2016).","DOI":"10.4238\/gmr.15018524"},{"key":"32","unstructured":"32) Pietrangelo A, Montosi G, Garuti C, Contri M, Giovannini F, Ceccarelli D, Masini A. Iron-induced oxidant stress in nonparenchymal liver cells: mitochondrial derangement and fibrosis in acutely iron-dosed gerbils and its prevention by silybin. <i>J. Bioenerg. Biomembr.<\/i>, <b>34<\/b>, 67\u201379 (2002)."},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Weiskirchen R, Tacke F. Relevance of autophagy in parenchymal and non-parenchymal liver cells for health and disease. <i>Cells<\/i>, <b>8<\/b>, 16 (2019).","DOI":"10.3390\/cells8010016"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Zhou X, Chan SW, Tseng HL, Deng Y, Hoi PM, Choi PS, Or PM, Yang JM, Lam FF, Lee SM, Leung GP, Kong SK, Ho HP, Kwan YW, Yeung JH. Danshensu is the major marker for the antioxidant and vasorelaxation effects of Danshen (<i>Salvia miltiorrhiza<\/i>) water-extracts produced by different heat water-extractions. <i>Phytomedicine<\/i>, <b>19<\/b>, 1263\u20131269 (2012).","DOI":"10.1016\/j.phymed.2012.08.011"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Teng MC, Wu PC, Lin SP, Wu CY, Wang PH, Chen CT, Chen BY. Danshensu decreases UVB-induced corneal inflammation in an experimental mouse model <i>via<\/i> oral administration. <i>Curr. Eye Res.<\/i>, <b>43<\/b>, 27\u201334 (2018).","DOI":"10.1080\/02713683.2017.1379543"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Liu H, Ma S, Xia H, Lou H, Zhu F, Sun L. Anti-inflammatory activities and potential mechanisms of phenolic acids isolated from <i>Salvia miltiorrhiza<\/i> f. <i>alba<\/i> roots in THP-1 macrophages. <i>J. Ethnopharmacol.<\/i>, <b>222<\/b>, 201\u2013207 (2018).","DOI":"10.1016\/j.jep.2018.05.008"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Fabregat I, Moreno-Caceres J, Sanchez A, Dooley S, Dewidar B, Giannelli G, Ten Dijke P. TGF-beta signalling and liver disease. <i>FEBS J.<\/i>, <b>283<\/b>, 2219\u20132232 (2016).","DOI":"10.1111\/febs.13665"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Clark DA, Coker R. Transforming growth factor-beta (TGF-beta). <i>Int. J. Biochem. Cell Biol.<\/i>, <b>30<\/b>, 293\u2013298 (1998).","DOI":"10.1016\/S1357-2725(97)00128-3"},{"key":"39","unstructured":"39) Naugler WE, Karin M. The wolf in sheep\u2019s clothing: the role of interleukin-6 in immunity, inflammation and cancer. <i>Trends Mol. Med.<\/i>, <b>14<\/b>, 109\u2013119 (2008)."},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. <i>Blood<\/i>, <b>89<\/b>, 739\u2013761 (1997).","DOI":"10.1182\/blood.V89.3.739"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, Burt AD, Fleming KA. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. <i>N. Engl. J. Med.<\/i>, <b>339<\/b>, 417\u2013423 (1998).","DOI":"10.1056\/NEJM199808133390701"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Zhao GR, Zhang HM, Ye TX, Xiang ZJ, Yuan YJ, Guo ZX, Zhao LB. Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B. <i>Food Chem. Toxicol.<\/i>, <b>46<\/b>, 73\u201381 (2008).","DOI":"10.1016\/j.fct.2007.06.034"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/6\/43_b19-01084\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,6]],"date-time":"2020-06-06T03:20:25Z","timestamp":1591413625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/6\/43_b19-01084\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b19-01084","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}