{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:57:57Z","timestamp":1781287077924,"version":"3.54.1"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Changsha Municipal Natural Science Foundation of Hunan Provincial of the People\u2019s Republic of China","award":["kq2007077"],"award-info":[{"award-number":["kq2007077"]}]},{"name":"National Science Foundation of Hunan Province of the People\u2019s Republic of China","award":["2026JJ81934"],"award-info":[{"award-number":["2026JJ81934"]}]},{"name":"National Science Foundation of Hunan Province of the People\u2019s Republic of China","award":["2026JJ81935"],"award-info":[{"award-number":["2026JJ81935"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Intrauterine growth restriction (IUGR) is associated with long-term metabolic programming effects, including hepatic structural alterations and later-life susceptibility to metabolic disease, potentially involving dysregulation of peroxisome proliferator-activated receptor alpha (PPAR\u03b1), a key regulator of hepatic fatty acid oxidation. Given its established antioxidant and lipid-modulating properties in adult models of metabolic syndrome, puerarin, a natural isoflavone, was evaluated as an early-life intervention to mitigate hepatic injury in IUGR offspring. An IUGR rat model was established via gestational protein restriction. Male offspring were randomized into Control, IUGR, and IUGR plus puerarin groups. Separate cohorts (n\u2009=\u20096 per group per time point) were assessed at weeks 3, 8, and 12. Puerarin (50 mg\/kg\/day) was administered intraperitoneally from postnatal days 7\u201321. Hepatic tissue characteristics were evaluated using T1 mapping and intravoxel incoherent motion (IVIM) MRI. Serum lipid profiles and hepatic PPAR\u03b1 mRNA expression were also measured. Data were analyzed using two-way ANOVA followed by Tukey\u2019s post hoc test. IUGR offspring exhibited significantly elevated hepatic T1 relaxation times from week 3 onward (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001), indicating early and persistent hepatic microstructural alterations. Serum lipid parameters remained largely comparable across all groups, with no significant intergroup differences in TG, TC, LDL-C, or HDL-C at individual time points. Puerarin treatment significantly reduced T1 values and improved diffusion-related parameter (D) across all time points (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), indicating improved hepatic water mobility and microstructural integrity. ADC showed early improvement at week 3, whereas perfusion-related IVIM parameters (D* and F) showed no consistent or significant intergroup differences. Serum TG levels were significantly reduced by puerarin at week 12 compared with untreated IUGR offspring (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), while TC and LDL-C remained unchanged. Hepatic PPAR\u03b1 expression was markedly suppressed in IUGR offspring across all time points (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and was significantly increased by puerarin only at week 12 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01), although overall expression remained below control levels. These findings suggest that IUGR primarily induces early hepatic microstructural alterations detectable by quantitative MRI before overt systemic dyslipidemia. Early-life puerarin intervention partially ameliorates hepatic diffusion abnormalities and improves selected metabolic markers, potentially through delayed activation of lipid oxidation pathways including PPAR\u03b1. However, further studies incorporating direct hepatic lipid quantification and functional metabolic assessments are required to validate these findings.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0350859","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:25:29Z","timestamp":1781285129000},"page":"e0350859","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling Puerarin\u2019s impact on MRI hepatic lipid deposition and serum lipids in IUGR offspring rats"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3654-9471","authenticated-orcid":true,"given":"Kalonda Alpha","family":"Mutamba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-9932","authenticated-orcid":true,"given":"DuJun","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-5718","authenticated-orcid":true,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Ri","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"pone.0350859.ref001","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4137\/CMPed.S40070","article-title":"Intrauterine growth restriction: antenatal and postnatal aspects","volume":"10","author":"D Sharma","year":"2016","journal-title":"Clin Med Insights Pediatr"},{"key":"pone.0350859.ref002","doi-asserted-by":"crossref","first-page":"269853","DOI":"10.1155\/2011\/269853","article-title":"Intrauterine growth retardation and nonalcoholic Fatty liver disease in children","volume":"2011","author":"A Alisi","year":"2011","journal-title":"Int J Endocrinol"},{"issue":"27","key":"pone.0350859.ref003","article-title":"The incidence rate, high-risk factors, and short- and long-term adverse outcomes of fetal growth restriction: a report from Mainland China","volume":"93","author":"J Liu","year":"2014","journal-title":"Medicine (Baltimore)"},{"key":"pone.0350859.ref004","doi-asserted-by":"crossref","first-page":"115209","DOI":"10.1016\/j.ecoenv.2023.115209","article-title":"Association between prenatal exposure to perfluoroalkyl substance mixtures and intrauterine growth restriction risk: a large, nested case-control study in Guangxi, China","volume":"262","author":"C Chen","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"issue":"13","key":"pone.0350859.ref005","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.12998\/wjcc.v11.i13.2855","article-title":"Long-term implications of fetal growth restriction","volume":"11","author":"M D\u2019Agostin","year":"2023","journal-title":"World J Clin Cases"},{"issue":"10","key":"pone.0350859.ref006","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.2337\/dc07-0281","article-title":"Intrauterine growth retardation, insulin resistance, and nonalcoholic fatty liver disease in children","volume":"30","author":"V Nobili","year":"2007","journal-title":"Diabetes Care"},{"key":"pone.0350859.ref007","doi-asserted-by":"crossref","first-page":"1040742","DOI":"10.3389\/fped.2022.1040742","article-title":"Therapeutic advances in overcoming intrauterine growth restriction induced metabolic syndrome","volume":"10","author":"AK Mutamba","year":"2023","journal-title":"Front Pediatr"},{"issue":"3","key":"pone.0350859.ref008","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqaf007","article-title":"Hepatic and pancreatic cellular response to early life nutritional mismatch","volume":"166","author":"S Ghosh","year":"2025","journal-title":"Endocrinology"},{"issue":"5","key":"pone.0350859.ref009","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1172\/JCI127502","article-title":"Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice","volume":"130","author":"DF De Jesus","year":"2020","journal-title":"J Clin Invest"},{"key":"pone.0350859.ref010","doi-asserted-by":"crossref","first-page":"801544","DOI":"10.3389\/fped.2022.801544","article-title":"Analysis of gene expression profiles in the liver of rats with intrauterine growth retardation","volume":"10","author":"Z Shen","year":"2022","journal-title":"Front Pediatr"},{"issue":"3","key":"pone.0350859.ref011","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajog.2008.05.022","article-title":"Down-regulation of transcription factor peroxisome proliferator-activated receptor in programmed hepatic lipid dysregulation and inflammation in intrauterine growth-restricted offspring","volume":"199","author":"TR Magee","year":"2008","journal-title":"Am J Obstet Gynecol"},{"issue":"7","key":"pone.0350859.ref012","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/ptr.5083","article-title":"Puerarin: a review of pharmacological effects","volume":"28","author":"Y-X Zhou","year":"2014","journal-title":"Phytother Res"},{"issue":"10","key":"pone.0350859.ref013","first-page":"1124","article-title":"Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats","volume":"17","author":"L-H Chen","year":"2015","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"issue":"11","key":"pone.0350859.ref014","article-title":"Pharmacological activity, pharmacokinetics, and clinical research progress of puerarin","volume":"11","author":"D Wang","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"pone.0350859.ref015","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev.nutr.012809.104755","article-title":"Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals","volume":"30","author":"BB Aggarwal","year":"2010","journal-title":"Annu Rev Nutr"},{"issue":"9","key":"pone.0350859.ref016","first-page":"670","article-title":"Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8","volume":"21","author":"Y Hu","year":"2023","journal-title":"Chin J Nat Med"},{"issue":"23","key":"pone.0350859.ref017","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.3390\/foods11233941","article-title":"A review of the effects of puerarin on glucose and lipid metabolism in metabolic syndrome: mechanisms and opportunities","volume":"11","author":"X Jing","year":"2022","journal-title":"Foods"},{"issue":"3","key":"pone.0350859.ref018","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3892\/ijmm.2015.2074","article-title":"Puerarin ameliorates hepatic steatosis by activating the PPAR\u03b1 and AMPK signaling pathways in hepatocytes","volume":"35","author":"O-H Kang","year":"2015","journal-title":"Int J Mol Med"},{"issue":"1","key":"pone.0350859.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41387-017-0009-6","article-title":"Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats","volume":"8","author":"X-F Chen","year":"2018","journal-title":"Nutr Diabetes"},{"key":"pone.0350859.ref020","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejphar.2017.05.055","article-title":"Puerarin promotes ABCA1-mediated cholesterol efflux and decreases cellular lipid accumulation in THP-1 macrophages","volume":"811","author":"C-H Li","year":"2017","journal-title":"Eur J Pharmacol"},{"issue":"3","key":"pone.0350859.ref021","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s00261-019-02382-9","article-title":"T1 mapping, T2 mapping and MR elastography of the liver for detection and staging of liver fibrosis","volume":"45","author":"DH Hoffman","year":"2020","journal-title":"Abdom Radiol (NY)"},{"issue":"27","key":"pone.0350859.ref022","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.3748\/wjg.v24.i27.3013","article-title":"Liver intravoxel incoherent motion diffusion-weighted imaging for the assessment of hepatic steatosis and fibrosis in children","volume":"24","author":"HJ Shin","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"2","key":"pone.0350859.ref023","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0254-6272(16)30029-2","article-title":"Puerarin affects bone biomarkers in the serum of rats with intrauterine growth restriction","volume":"36","author":"J Chen","year":"2016","journal-title":"J Tradit Chin Med"},{"issue":"5","key":"pone.0350859.ref024","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/pr.2014.117","article-title":"Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats","volume":"76","author":"EK Zinkhan","year":"2014","journal-title":"Pediatr Res"},{"issue":"6","key":"pone.0350859.ref025","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1017\/S0007114519001508","article-title":"Curcumin attenuates insulin resistance and hepatic lipid accumulation in a rat model of intra-uterine growth restriction through insulin signalling pathway and sterol regulatory element binding proteins","volume":"122","author":"Y Niu","year":"2019","journal-title":"Br J Nutr"},{"key":"pone.0350859.ref026","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/bs.irn.2017.02.009","article-title":"Effect of Chinese herbal medicine on molecular imaging of neurological disorders","volume":"135","author":"Y Yao","year":"2017","journal-title":"Int Rev Neurobiol"},{"key":"pone.0350859.ref027","doi-asserted-by":"crossref","first-page":"1279029","DOI":"10.3389\/fmicb.2023.1279029","article-title":"Puerarin alleviates inflammation and pathological damage in colitis mice by regulating metabolism and gut microbiota","volume":"14","author":"Y Zou","year":"2023","journal-title":"Front Microbiol"},{"issue":"6","key":"pone.0350859.ref028","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3390\/molecules22060939","article-title":"Pharmacokinetics and tissue distribution kinetics of puerarin in rats using indirect competitive ELISA","volume":"22","author":"H Kong","year":"2017","journal-title":"Molecules"},{"issue":"1","key":"pone.0350859.ref029","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40360-018-0216-3","article-title":"Absolute oral bioavailability and disposition kinetics of puerarin in female rats","volume":"19","author":"T Anukunwithaya","year":"2018","journal-title":"BMC Pharmacol Toxicol"},{"issue":"5","key":"pone.0350859.ref030","doi-asserted-by":"crossref","first-page":"513","DOI":"10.30802\/AALAS-JAALAS-18-000005","article-title":"Sex- and strain-related differences in the stress response of mice to CO\u2082 euthanasia","volume":"57","author":"MA Creamer-Hente","year":"2018","journal-title":"J Am Assoc Lab Anim Sci"},{"issue":"1","key":"pone.0350859.ref031","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41398-023-02322-8","article-title":"Low protein-induced intrauterine growth restriction as a risk factor for schizophrenia phenotype in a rat model: assessing the role of oxidative stress and neuroinflammation interaction","volume":"13","author":"L Allg\u00e4uer","year":"2023","journal-title":"Transl Psychiatry"},{"key":"pone.0350859.ref032","doi-asserted-by":"crossref","first-page":"991383","DOI":"10.3389\/fcvm.2022.991383","article-title":"Quantitative MRI in cardiometabolic disease: from conventional cardiac and liver tissue mapping techniques to multi-parametric approaches","volume":"9","author":"A Fotaki","year":"2023","journal-title":"Front Cardiovasc Med"},{"issue":"2","key":"pone.0350859.ref033","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/jmri.27822","article-title":"Staging liver fibrosis: comparison of native T1 mapping, T2 mapping, and T1rho: an experimental study in rats with bile duct ligation and carbon tetrachloride at 11.7 T MRI","volume":"55","author":"Y Lu","year":"2022","journal-title":"J Magn Reson Imaging"},{"issue":"1","key":"pone.0350859.ref034","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00330-019-06335-0","article-title":"Native T1 mapping compared to ultrasound elastography for staging and monitoring liver fibrosis: an animal study of repeatability, reproducibility, and accuracy","volume":"30","author":"J Li","year":"2020","journal-title":"Eur Radiol"},{"issue":"1","key":"pone.0350859.ref035","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1148\/radiol.2020192118","article-title":"Advanced MRI of liver fibrosis and treatment response in a rat model of nonalcoholic steatohepatitis","volume":"296","author":"IY Zhou","year":"2020","journal-title":"Radiology"},{"issue":"2","key":"pone.0350859.ref036","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1148\/radiol.13130420","article-title":"Apparent diffusion coefficient and beyond: what diffusion MR imaging can tell us about tissue structure","volume":"268","author":"D Le Bihan","year":"2013","journal-title":"Radiology"},{"issue":"1","key":"pone.0350859.ref037","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/s12876-022-02517-1","article-title":"Multi-parametric magnetic resonance imaging of liver regeneration in a standardized partial hepatectomy rat model","volume":"22","author":"C Qiu","year":"2022","journal-title":"BMC Gastroenterol"},{"issue":"10","key":"pone.0350859.ref038","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1007\/s00330-023-10052-0","article-title":"Impact of fat on the apparent T1 value of the liver: assessment by water-only derived T1 mapping","volume":"33","author":"M Higashi","year":"2023","journal-title":"Eur Radiol"},{"issue":"1","key":"pone.0350859.ref039","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12968-016-0313-7","article-title":"Histologic validation of myocardial fibrosis measured by T1 mapping: a systematic review and meta-analysis","volume":"18","author":"K-Y Diao","year":"2016","journal-title":"J Cardiovasc Magn Reson"},{"issue":"6","key":"pone.0350859.ref040","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1002\/jmri.27891","article-title":"Editorial for \u201cHepatic steatosis has no effect in diagnosis accuracy of LI-RADS v2018 categorization of hepatocellular carcinoma in MR imaging\u201d","volume":"55","author":"G Pag\u00e9","year":"2022","journal-title":"J Magn Reson Imaging"},{"issue":"10","key":"pone.0350859.ref041","first-page":"1230","article-title":"Reference range of quantitative MRI metrics corrected T1 and Liver fat content in children and young adults: pooled participant analysis","volume":"11","author":"E Shumbayawonda","year":"2024","journal-title":"Children (Basel)"},{"issue":"4","key":"pone.0350859.ref042","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/mrm.25639","article-title":"Improved T1, contrast concentration, and pharmacokinetic parameter quantification in the presence of fat with two-point Dixon for dynamic contrast-enhanced magnetic resonance imaging","volume":"75","author":"Y Le","year":"2016","journal-title":"Magn Reson Med"},{"issue":"1","key":"pone.0350859.ref043","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/jmri.25146","article-title":"Influence of fat on liver T1 measurements using modified Look-Locker inversion recovery (MOLLI) methods at 3T","volume":"44","author":"FE Mozes","year":"2016","journal-title":"J Magn Reson Imaging"},{"key":"pone.0350859.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mri.2021.03.015","article-title":"Effect of hepatic steatosis on native T1 mapping of 3T magnetic resonance imaging in the assessment of T1 values for patients with non-alcoholic fatty liver disease","volume":"80","author":"J-H Ahn","year":"2021","journal-title":"Magn Reson Imaging"},{"issue":"1","key":"pone.0350859.ref045","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12944-023-01969-y","article-title":"Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation","volume":"22","author":"M Yang","year":"2023","journal-title":"Lipids Health Dis"},{"issue":"3","key":"pone.0350859.ref046","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0173149","article-title":"Diminished liver microperfusion in Fontan patients: a biexponential DWI study","volume":"12","author":"H Dijkstra","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"pone.0350859.ref047","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/jmri.25663","article-title":"Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: a MAGNET study","volume":"46","author":"P Manning","year":"2017","journal-title":"J Magn Reson Imaging"},{"key":"pone.0350859.ref048","doi-asserted-by":"crossref","first-page":"155713","DOI":"10.1016\/j.metabol.2023.155713","article-title":"Glucocorticoids and intrauterine programming of nonalcoholic fatty liver disease","volume":"150","author":"Z Chen","year":"2024","journal-title":"Metabolism"},{"issue":"6","key":"pone.0350859.ref049","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/sj.mn.7800206","article-title":"Impairment of hepatic microcirculation in fatty liver","volume":"10","author":"S Ijaz","year":"2003","journal-title":"Microcirculation"},{"issue":"2","key":"pone.0350859.ref050","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/hep.20302","article-title":"Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice","volume":"40","author":"RS McCuskey","year":"2004","journal-title":"Hepatology"},{"issue":"10","key":"pone.0350859.ref051","article-title":"Nonalcoholic fatty liver disease: correlation of the liver parenchyma fatty acid with intravoxel incoherent motion mr imaging-an experimental study in a rat model","volume":"10","author":"S-M Yu","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"pone.0350859.ref052","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1148\/radiol.13122506","article-title":"Nonalcoholic fatty liver disease: intravoxel incoherent motion diffusion-weighted MR imaging-an experimental study in a rabbit model","volume":"270","author":"I Joo","year":"2014","journal-title":"Radiology"},{"issue":"1","key":"pone.0350859.ref053","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/RCT.0b013e3182a589be","article-title":"Evaluation of hepatic fibrosis using intravoxel incoherent motion in diffusion-weighted liver MRI","volume":"38","author":"JH Yoon","year":"2014","journal-title":"J Comput Assist Tomogr"},{"issue":"2","key":"pone.0350859.ref054","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/pr.2012.173","article-title":"Plasma lipid levels and body weight altered by intrauterine growth restriction and postnatal fructose diet in adult rats","volume":"73","author":"E Malo","year":"2013","journal-title":"Pediatr Res"},{"issue":"5","key":"pone.0350859.ref055","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1210\/me.2010-0395","article-title":"Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7alpha-hydroxylase promoter","volume":"25","author":"G Sohi","year":"2011","journal-title":"Mol Endocrinol"},{"key":"pone.0350859.ref056","doi-asserted-by":"crossref","first-page":"956688","DOI":"10.3389\/fimmu.2022.956688","article-title":"Puerarin ameliorates nonalcoholic fatty liver in rats by regulating hepatic lipid accumulation, oxidative stress, and inflammation","volume":"13","author":"J Zhou","year":"2022","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0350859.ref057","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.lfs.2006.01.016","article-title":"Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats","volume":"79","author":"L-P Yan","year":"2006","journal-title":"Life Sci"},{"issue":"4","key":"pone.0350859.ref058","first-page":"273","article-title":"Hypocholesterolemic effect of total isoflavones from Pueraria lobata in ovariectomized rats","volume":"25","author":"G Zheng","year":"2002","journal-title":"Zhong Yao Cai"},{"issue":"3","key":"pone.0350859.ref059","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jhep.2004.11.032","article-title":"Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells","volume":"42","author":"M Hoekstra","year":"2005","journal-title":"J Hepatol"},{"key":"pone.0350859.ref060","doi-asserted-by":"crossref","first-page":"1598897","DOI":"10.3389\/fnut.2025.1598897","article-title":"Puerarin as a multi-targeted modulator of lipid metabolism: molecular mechanisms, therapeutic potential and prospects for nutritional translation","volume":"12","author":"S Ou","year":"2025","journal-title":"Front Nutr"},{"key":"pone.0350859.ref061","article-title":"Role of PPARs in the regulation of obesity-related insulin sensitivity and inflammation","author":"DE Moller","year":"2003","journal-title":"Int J Obes Relat Metab Disord"},{"issue":"3","key":"pone.0350859.ref062","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4161\/adip.20035","article-title":"Distinct roles for alpha-beta hydrolase domain 5 (ABHD5\/CGI-58) and adipose triglyceride lipase (ATGL\/PNPLA2) in lipid metabolism and signaling","volume":"1","author":"CC Lord","year":"2012","journal-title":"Adipocyte"},{"key":"pone.0350859.ref063","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.biochem.77.061307.091829","article-title":"Fat and beyond: the diverse biology of PPARgamma","volume":"77","author":"P Tontonoz","year":"2008","journal-title":"Annu Rev Biochem"},{"key":"pone.0350859.ref064","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mce.2009.09.014","article-title":"PPARs and adipocyte function","volume":"318","author":"C Christodoulides","year":"2010","journal-title":"Mol Cell Endocrinol"},{"issue":"1","key":"pone.0350859.ref065","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/mnfr.201200522","article-title":"Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors","volume":"57","author":"T Goto","year":"2013","journal-title":"Mol Nutr Food Res"},{"issue":"11","key":"pone.0350859.ref066","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1182\/blood-2003-11-3791","article-title":"Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro","volume":"103","author":"R Kleemann","year":"2004","journal-title":"Blood"},{"issue":"2","key":"pone.0350859.ref067","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1172\/JCI200422422","article-title":"Molecular mediators of hepatic steatosis and liver injury","volume":"114","author":"JD Browning","year":"2004","journal-title":"J Clin Invest"},{"key":"pone.0350859.ref068","doi-asserted-by":"crossref","first-page":"117319","DOI":"10.1016\/j.biopha.2024.117319","article-title":"Protective effects of puerarin on metabolic diseases: emphasis on the therapeutical effects and the underlying molecular mechanisms","volume":"179","author":"Q Wan","year":"2024","journal-title":"Biomed Pharmacother"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:25:43Z","timestamp":1781285143000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350859"}},"subtitle":[],"editor":[{"given":"Ewa","family":"Tomaszewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":68,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0350859","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]}}}