{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:33:52Z","timestamp":1776087232012,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K00844, 20K02402"],"award-info":[{"award-number":["16K00844, 20K02402"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum triglycerides, total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-\u03b1, IL-6, and IL-1\u03b2 in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.<\/jats:p>","DOI":"10.3390\/nu12051541","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T11:42:02Z","timestamp":1590406922000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Blackcurrant (Ribes nigrum) Extract Prevents Dyslipidemia and Hepatic Steatosis in Ovariectomized Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4729-3432","authenticated-orcid":false,"given":"Naoki","family":"Nanashima","sequence":"first","affiliation":[{"name":"Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanako","family":"Yamanouchi","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3428-6719","authenticated-orcid":false,"given":"Toshiko","family":"Tomisawa","sequence":"additional","affiliation":[{"name":"Department of Nursing Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Department of Nursing Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-0495","authenticated-orcid":false,"given":"Indrawati","family":"Oey","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Otago, PO Box 56, Dunedin 9054, New Zealand"},{"name":"Riddet Institute, Private Bag 11 222, Palmerston North 4442, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-6250","authenticated-orcid":false,"given":"Hayato","family":"Maeda","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki 036-8561, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1016\/j.celrep.2018.02.041","article-title":"Estrogen Deficiency Promotes Hepatic Steatosis via a Glucocorticoid Receptor-Dependent Mechanism in Mice","volume":"22","author":"Quinn","year":"2018","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.steroids.2017.10.015","article-title":"Estrogens and female liver health","volume":"133","author":"Chen","year":"2018","journal-title":"Steroids"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.maturitas.2008.02.008","article-title":"Metabolic syndrome after menopause and the role of hormones","volume":"60","author":"Lobo","year":"2008","journal-title":"Maturitas"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/MOL.0b013e3283613a94","article-title":"Cholesterol and atherosclerosis: Modulation by oestrogen","volume":"24","author":"Barton","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s11886-015-0609-5","article-title":"Dyslipidemia and cardiovascular disease in women","volume":"17","author":"Cifkova","year":"2015","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.coph.2013.01.005","article-title":"Menopause, atherosclerosis, and coronary artery disease","volume":"13","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1055\/s-0033-1358519","article-title":"Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease","volume":"33","author":"Cohen","year":"2013","journal-title":"Semin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: Current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat. Rev. Gastroenterol Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-3-319-70178-3_12","article-title":"Role of Estrogens in the Regulation of Liver Lipid Metabolism","volume":"1043","author":"Palmisano","year":"2017","journal-title":"Adv. Exp. Med Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jsbmb.2013.12.010","article-title":"Soy isoflavones and prostate cancer: A review of molecular mechanisms","volume":"140","author":"Mahmoud","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lee, Y.M., Kim, J.B., Bae, J.H., Lee, J.S., Kim, P.S., Jang, H.H., and Kim, H.R. (2012). Estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb. in MCF-7 cells. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-260"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jep.2011.09.034","article-title":"Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu)","volume":"138","author":"Guo","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/bcr781","article-title":"Phyto-oestrogens and breast cancer chemoprevention","volume":"6","author":"Limer","year":"2004","journal-title":"Breast Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0378-5122(95)00937-G","article-title":"Phytoestrogens\u2014A short review","volume":"22","author":"Knight","year":"1995","journal-title":"Maturitas"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nanashima, N., Horie, K., and Maeda, H. (2017). Phytoestrogenic Activity of Blackcurrant Anthocyanins Is Partially Mediated through Estrogen Receptor Beta. Molecules, 23.","DOI":"10.3390\/molecules23010074"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1002\/mnfr.201500479","article-title":"Phytoestrogenic activity of blackcurrant (Ribes nigrum) anthocyanins is mediated through estrogen receptor alpha","volume":"59","author":"Nanashima","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1039\/c2fo30058c","article-title":"The health benefits of blackcurrants","volume":"3","author":"Gopalan","year":"2012","journal-title":"Food Funct."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nanashima, N., Horie, K., Maeda, H., Tomisawa, T., Kitajima, M., and Nakamura, T. (2018). Blackcurrant Anthocyanins Increase the Levels of Collagen, Elastin, and Hyaluronic Acid in Human Skin Fibroblasts and Ovariectomized Rats. Nutrients, 10.","DOI":"10.3390\/nu10040495"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nanashima, N., and Horie, K. (2019). Blackcurrant Extract with Phytoestrogen Activity Alleviates Hair Loss in Ovariectomized Rats. Molecules, 24.","DOI":"10.3390\/molecules24071272"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Horie, K., Nanashima, N., and Maeda, H. (2019). Phytoestrogenic Effects of Blackcurrant Anthocyanins Increased Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells and Ovariectomized Rats. Molecules, 24.","DOI":"10.3390\/molecules24071259"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/oby.22353","article-title":"Blackcurrant (Ribes nigrum) Prevents Obesity-Induced Nonalcoholic Steatohepatitis in Mice","volume":"27","author":"Lee","year":"2019","journal-title":"Obesity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1017\/S0007114515001105","article-title":"Polyphenol-rich blackcurrant extract exerts hypocholesterolaemic and hypoglycaemic effects in mice fed a diet containing high fat and cholesterol","volume":"113","author":"Benn","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Nonalcoholic Steatohepatitis Clinical Research, N. Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11162","DOI":"10.1038\/srep11162","article-title":"Central blockade of salusin beta attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.maturitas.2011.12.016","article-title":"Sex hormones, appetite and eating behaviour in women","volume":"71","author":"Hirschberg","year":"2012","journal-title":"Maturitas"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35983","DOI":"10.1074\/jbc.M507339200","article-title":"Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways","volume":"280","author":"Souza","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jep.2017.12.027","article-title":"Curcuma comosa reduces visceral adipose tissue and improves dyslipidemia in ovariectomized rats","volume":"215","author":"Sutjarit","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.fct.2017.05.059","article-title":"The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice","volume":"106","author":"Kim","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1097\/GME.0000000000001403","article-title":"Lipid profile differences during menopause: A review with meta-analysis","volume":"26","author":"Ambikairajah","year":"2019","journal-title":"Menopause"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jeong, Y.H., Hur, H.J., Jeon, E.J., Park, S.J., Hwang, J.T., Lee, A.S., Lee, K.W., and Sung, M.J. (2018). Honokiol Improves Liver Steatosis in Ovariectomized Mice. Molecules, 23.","DOI":"10.3390\/molecules23010194"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exger.2018.09.027","article-title":"The decline of whole-body glucose metabolism in ovariectomized rats","volume":"113","author":"Min","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.maturitas.2016.11.019","article-title":"Ovarian aging in women with diabetes: An overview","volume":"96","author":"Wellons","year":"2017","journal-title":"Maturitas"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yanai, H., and Yoshida, H. (2019). Beneficial Effects of Adiponectin on Glucose and Lipid Metabolism and Atherosclerotic Progression: Mechanisms and Perspectives. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051190"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Landecho, M.F., Tuero, C., Valenti, V., Bilbao, I., de la Higuera, M., and Fruhbeck, G. (2019). Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk. Nutrients, 11.","DOI":"10.3390\/nu11112664"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.metabol.2015.01.019","article-title":"Chronic angiotensin AT2R activation prevents high-fat diet-induced adiposity and obesity in female mice independent of estrogen","volume":"64","author":"Nag","year":"2015","journal-title":"Metabolism"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10522-004-3190-7","article-title":"Estradiol and progesterone treatments change the lipid profile in naturally menopausal rats from different age groups","volume":"5","author":"Moorthy","year":"2004","journal-title":"Biogerontology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2337\/diabetes.52.2.268","article-title":"Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin","volume":"52","author":"Combs","year":"2003","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12011-015-0475-4","article-title":"High-Fat Diet Increased Renal and Hepatic Oxidative Stress Induced by Vanadium of Wistar Rat","volume":"170","author":"Wang","year":"2016","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tan, B.L., and Norhaizan, M.E. (2019). Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function. Nutrients, 11.","DOI":"10.3390\/nu11112579"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, C., Sun, J., Lu, Y., and Bo, Y. (2016). Effects of Anthocyanin on Serum Lipids in Dyslipidemia Patients: A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162089"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.nut.2016.01.007","article-title":"Dietary sweet cherry anthocyanins attenuates diet-induced hepatic steatosis by improving hepatic lipid metabolism in mice","volume":"32","author":"Song","year":"2016","journal-title":"Nutrition"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1038\/s41598-020-59485-3","article-title":"Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease","volume":"10","author":"Musolino","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.bbrc.2009.01.058","article-title":"Flavanone exhibits PPARgamma ligand activity and enhances differentiation of 3T3-L1 adipocytes","volume":"380","author":"Saito","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37007","DOI":"10.1289\/EHP3444","article-title":"The Role of Dietary Phytoestrogens and the Nuclear Receptor PPARgamma in Adipogenesis: An in Vitro Study","volume":"127","author":"Hall","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1039\/c3fo60063g","article-title":"Flavonoids as dietary regulators of nuclear receptor activity","volume":"4","author":"Avior","year":"2013","journal-title":"Food Funct."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:32:23Z","timestamp":1760175143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,25]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["nu12051541"],"URL":"https:\/\/doi.org\/10.3390\/nu12051541","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,25]]}}}