{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:26:48Z","timestamp":1762075608193,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean National Research Foundation of Korea (NRF)","award":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"],"award-info":[{"award-number":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"]}]},{"name":"Korean Hypertension Society (2021)","award":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"],"award-info":[{"award-number":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"]}]},{"name":"BK21 FOUR education program","award":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"],"award-info":[{"award-number":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"]}]},{"name":"National Natural Science Foundation of China","award":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"],"award-info":[{"award-number":["NRF-2019R1A2C1005720","NSFC 31660284","NSFC 31860288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 \u03bcg\/kg\/min) on GD 8 increased systolic and diastolic blood pressures and reduced fetal weight and placental weight. The diameters of the glomeruli were expended and glomeruli capillaries were diminished. No change was observed in the heart and liver in the Ang II group, but epithelial structures were disrupted in the uterus. Ech A treatment on GD 14 (100 \u03bcg\/\u03bcL) through the jugular vein reduced systolic and diastolic blood pressures and reversed glomerulus alterations, but the fetal or placental parameters were unaffected. Ech A only partly reversed the effect on the uterus. The mRNA expression of TNF\u2013\u03b1 was increased and IL\u201310 and VEGF were reduced in the uterus of the Ang II group, while Ech A restored these changes. A similar trend was observed in the kidney, liver, and heart of this group. Furthermore, Bcl\u20132 was reduced and Bcl\u20132\/Bax ratios were significantly reduced in the kidney and heart of the Ang II group, while Ech A reversed these changes. We suggest that Ech A modulates inflammation and apoptosis in key systemic organs in Ang II-induced rat preeclampsia and preserves kidney and uterus structures and reduces blood pressure.<\/jats:p>","DOI":"10.3390\/md20110722","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T06:02:29Z","timestamp":1668751349000},"page":"722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Echinochrome A Reverses Kidney Abnormality and Reduces Blood Pressure in a Rat Model of Preeclampsia"],"prefix":"10.3390","volume":"20","author":[{"given":"Huixing","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea"},{"name":"Department of Research Center, Yanbian University Hospital, Yanji 133000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-8132","authenticated-orcid":false,"given":"Junxian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea"},{"name":"Department of Research Center, Yanbian University Hospital, Yanji 133000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7526-026X","authenticated-orcid":false,"given":"Elena","family":"Vasileva","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-574X","authenticated-orcid":false,"given":"Natalia","family":"Mishchenko","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-2099","authenticated-orcid":false,"given":"Sergey","family":"Fedoreyev","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Stonik","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0134","authenticated-orcid":false,"given":"Yinhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea"},{"name":"Department of Research Center, Yanbian University Hospital, Yanji 133000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.3892\/etm.2017.4143","article-title":"Upregulated unique long 16 binding protein 1 detected in preeclamptic placenta affects human extravillous trophoblast cell line (HTR-8\/SVneo) invasion by modulating the function of uterine natural killer cells","volume":"13","author":"Liu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1194\/jlr.M071985","article-title":"Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in pre-eclampsia","volume":"58","author":"Mistry","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shen, M., Smith, G.N., Rodger, M., White, R.R., Walker, M.C., Wen, S.W., and R\u00e4is\u00e4nen, S.H. (2017). Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175914"},{"key":"ref_4","first-page":"883","article-title":"Magnesium sulfate therapy in preeclampsia and eclampsia","volume":"92","author":"Witlin","year":"1998","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (2000). National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy. Am. J. Obstet. Gynecol., 183, S1\u2013S22.","DOI":"10.1067\/mob.2000.107928"},{"key":"ref_6","first-page":"181","article-title":"Diagnosis and management of gestational hypertension and preeclampsia","volume":"102","author":"Sibai","year":"2003","journal-title":"Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00006250-200212000-00037","article-title":"Chronic hypertension in pregnancy","volume":"100","author":"Sibai","year":"2002","journal-title":"Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/01.HYP.0000143849.67254.ca","article-title":"Short- and long-term changes in plasma inflammatory markers associated with preeclampsia","volume":"44","author":"Freeman","year":"2004","journal-title":"Hypertension"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1152\/physiol.00006.2013","article-title":"Elucidating immune mechanisms causing hypertension during pregnancy","volume":"28","author":"LaMarca","year":"2013","journal-title":"Physiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1600-0897.2010.00831.x","article-title":"Immunology of pre-eclampsia","volume":"63","author":"Redman","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/HYPERTENSIONAHA.113.01514","article-title":"Administration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy","volume":"62","author":"Cornelius","year":"2013","journal-title":"Hypertension"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1161\/HYPERTENSIONAHA.110.150540","article-title":"Autoantibody mediated angiotensin receptor activation contributes to preeclampsia through tumor necrosis factor-alpha signaling","volume":"55","author":"Irani","year":"2010","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1161\/01.HYP.0000169152.59854.36","article-title":"Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats","volume":"46","author":"LaMarca","year":"2005","journal-title":"Hypertension"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0889-8529(18)30059-8","article-title":"Immunologic response in pregnancy: Its role in endocrine disorders of pregnancy and influence on the course of maternal autoimmune diseases","volume":"24","author":"Formby","year":"1995","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1161\/01.HYP.0000238442.33463.94","article-title":"Hypertension produced by reductions in uterine perfusion in the pregnant rat: Role of interleukin 6","volume":"48","author":"Gadonski","year":"2006","journal-title":"Hypertension"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/ajh.2009.149","article-title":"Effects of 17-hydroxyprogesterone on tumor necrosis factor-alpha-induced hypertension during pregnancy","volume":"22","author":"Keiser","year":"2009","journal-title":"Am. J. Hypertens."},{"key":"ref_17","first-page":"65","article-title":"Hypertension in response to IL-6 during pregnancy: Role of AT1-receptor activation","volume":"201","author":"Lamarca","year":"2011","journal-title":"Int. J. Interf. Cytokine Mediat. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6024","DOI":"10.4049\/jimmunol.1004026","article-title":"Autoantibody-mediated IL-6-dependent endothelin-1 elevation underlies pathogenesis in a mouse model of preeclampsia","volume":"186","author":"Zhou","year":"2011","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jsgi.2005.02.005","article-title":"The predominant Th1 cytokine profile in maternal plasma of preeclamptic women is not reflected in the choriodecidual and fetal compartments","volume":"12","author":"Arriaga","year":"2005","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.4049\/jimmunol.163.6.3491","article-title":"A deficiency of placental IL 10 in preeclampsia","volume":"163","author":"Hennessy","year":"1999","journal-title":"J. Immunol."},{"key":"ref_21","first-page":"105","article-title":"The role of immune activation in contributing to vascular dysfunction and the pathophysiology of hypertension during preeclampsia","volume":"62","author":"Lamarca","year":"2010","journal-title":"Minerva Ginecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0010-406X(69)91347-4","article-title":"Distribution of spinochrome pigments in echinoids","volume":"28","author":"Anderson","year":"1969","journal-title":"Comp. Biochem. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kim, H.K., Vasileva, E.A., Mishchenko, N.P., Fedoreyev, S.A., and Han, J. (2021). Multifaceted Clinical Effects of Echinochrome. Mar. Drugs, 19.","DOI":"10.3390\/md19080412"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Malyarenko, T.V., Kicha, A.A., Stonik, V.A., and Ivanchina, N.V. (2021). Sphingolipids of Asteroidea and Holothuroidea: Structures and Biological Activities. Mar. Drugs, 19.","DOI":"10.3390\/md19060330"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s11101-018-9547-3","article-title":"Naphthoquinone pigments from sea urchins: Chemistry and pharmacology","volume":"17","author":"Shikov","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111933","DOI":"10.1016\/j.jep.2019.111933","article-title":"Animal-derived medicinal products in Russia: Current nomenclature and specific aspects of quality control","volume":"240","author":"Prokopov","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","first-page":"821","article-title":"New Aminonaphthoquinone from the Sea Urchins Strongylocentrotus pallidus and Mesocentrotus nudus","volume":"11","author":"Vasileva","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Artyukov, A.A., Zelepuga, E.A., Bogdanovich, L.N., Lupach, N.M., Novikov, V.L., Rutckova, T.A., and Kozlovskaya, E.P. (2020). Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051494"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/978-1-4419-8059-5_14","article-title":"Echinoderm immunity","volume":"708","author":"Smith","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cho, K., Kang, M.C., Parveen, A., Yumnam, S., and Kim, S.Y. (2019). Anti-Inflammatory Effect of Chloroform Fraction of Pyrus Ussuriensis Maxim. Leaf Extract on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in nc\/nga Mice. Nutrients, 11.","DOI":"10.3390\/nu11020276"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s13273-019-0044-6","article-title":"The protective effects of Echinochrome A structural analogs against oxidative stress and doxorubicin in AC16 cardiomyocytes","volume":"15","author":"Yoon","year":"2019","journal-title":"Mol. Cell. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1021\/np049585r","article-title":"Echinamines A and B, first aminated hydroxynaphthazarins from the sea urchin Scaphechinus mirabilis","volume":"68","author":"Mischenko","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_33","first-page":"22","article-title":"Antioxidative activity of histochrome and some other drugs used in ophthalmology","volume":"115","author":"Babenkova","year":"1999","journal-title":"Vestn. Oftalmol."},{"key":"ref_34","first-page":"38","article-title":"The specific features of penetration of the antioxidant histochrome across the blood-ocular barrier: An experimental study","volume":"123","author":"Guseva","year":"2007","journal-title":"Vestn. Oftalmol."},{"key":"ref_35","first-page":"38","article-title":"Apoptosis and expression of Bcl-2, Bax, p53, caspase-3, and Fas, Fas ligand in placentas complicated by preeclampsia","volume":"38","author":"Mendilcioglu","year":"2011","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_36","first-page":"51","article-title":"Effects of emoxipine and histochrome on lipid peroxidation and activity of serum MB-creatine phosphokinase in patients with ischemic heart disease during aortocoronary shunting","volume":"60","author":"Lasukova","year":"1997","journal-title":"Eksp. Klin. Farmakol."},{"key":"ref_37","first-page":"32","article-title":"The effect of histochrome on the lipid peroxidation indices during the surgical treatment of patients with ischemic heart disease of different functional classes","volume":"62","author":"Lasukova","year":"1999","journal-title":"Eksp. Klin. Farmakol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.placenta.2005.05.003","article-title":"Placental deficiency of interleukin-10 (IL-10) in preeclampsia and its relationship to an IL10 promoter polymorphism","volume":"27","author":"Makris","year":"2006","journal-title":"Placenta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1161\/HYPERTENSIONAHA.111.172114","article-title":"Interleukin 10 deficiency exacerbates toll-like receptor 3-induced preeclampsia-like symptoms in mice","volume":"58","author":"Chatterjee","year":"2011","journal-title":"Hypertension"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000087965","article-title":"Lessons from reproductive immunology for other fields of immunology and clinical approaches","volume":"89","author":"Markert","year":"2005","journal-title":"Chem. Immunol. Allergy."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1600-0897.1998.tb00059.x","article-title":"Cytokine expression by first-trimester human chorionic villi","volume":"40","author":"Bennett","year":"1998","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.4049\/jimmunol.164.11.5721","article-title":"Gestational age-dependent expression of IL-10 and its receptor in human placental tissues and isolated cytotrophoblasts","volume":"164","author":"Hanna","year":"2000","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1053\/plac.2002.0930","article-title":"Pre-eclampsia, the placenta and the maternal systemic inflammatory response\u2014A review","volume":"24","author":"Redman","year":"2003","journal-title":"Placenta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.placenta.2010.12.005","article-title":"TNF-\u03b1 inhibits trophoblast integration into endothelial cellular networks","volume":"32","author":"Xu","year":"2011","journal-title":"Placenta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1210\/jc.2003-031351","article-title":"Tumor necrosis factor-alpha inhibits trophoblast migration through elevation of plasminogen activator inhibitor-1 in firsttrimester villous explant cultures","volume":"89","author":"Bauer","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/722\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:16Z","timestamp":1760145616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["md20110722"],"URL":"https:\/\/doi.org\/10.3390\/md20110722","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2022,11,17]]}}}