{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:38Z","timestamp":1792790498015,"version":"4.5.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with a complex and multifactorial pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to investigate the mecha-nism of liquiritin (LQ) in NAFLD for its treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study integrates bioinformatics analysis with\n                      <jats:italic>in vitro<\/jats:italic>\n                      validation. Bulk RNA-seq analysis and single-cell dataset analysis were performed using Gene Expression Omnibus database resources. Molecular docking and molecular dynamics simulations were employed to evaluate the binding affinity of liquiritin with lipid metabolism-related proteins AKT and FOXO1.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation was conducted using the HepG2, AML12 and RAW 264.7 to investigate the mechanism by which liquiritin regulates lipid metabolic homeostasis in HepG2 cells and AML12 cells via the AKT\/FOXO1 pathway through protein immunoblotting and immunofluorescence. The effects of liquiritin on mitochondrial autophagy in RAW 264.7 cells were also examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bulk RNA-seq analysis identified FOXO1 as a key target, while single-cell analysis predicted interactions between hepatocytes and macrophages in non-alcoholic fatty liver disease (NAFLD). Molecular docking predicted a potential stable interaction between liquiritin and FOXO1. In HepG2 cells and AML12 cells, liquiritin improved NAFLD lipid metabolism disorders by regulating the AKT\/FOXO1 pathway. Liquiritin also modulates the expression of mitophagy-associated proteins in RAW264.7 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Liquiritin improves lipid metabolism disorders in NAFLD by regulating the AKT\/FOXO1 pathway, while also potentially influencing macrophage function. This suggests its potential as a candidate therapeutic agent for non-alcoholic fatty liver disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1809617","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:46:54Z","timestamp":1781671614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Liquiritin restores metabolic homeostasis in NAFLD by modulating AKT1\/FOXO1 signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhirun","family":"Zhang","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Jiao","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuangzhuang","family":"Sun","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Shanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpeng","family":"Guo","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]},{"name":"Clinical College of Medicine, Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.14336\/ad.2021.0719","article-title":"Comparative analysis of aducanumab, zagotenemab and pioglitazone as targeted treatment strategies for alzheimer\u2019s disease","volume":"12","author":"Abyadeh","year":"2022","journal-title":"Aging Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/s41586-024-07537-3","article-title":"CTLA-4-expressing ILC3s restrain interleukin-23-mediated inflammation","volume":"630","author":"Ahmed","year":"2024","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3390\/antiox14080990","article-title":"Development of glycyrrhizic acid nanoparticles for modulating gastric ulcer healing: a comparative in vivo study targeting oxidative stress and inflammatory pathways","volume":"14","author":"Albalawi","year":"2025","journal-title":"Antioxidants"},{"key":"B4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12916-022-02457-3","article-title":"The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell\u2019s metabolic crosstalk","volume":"20","author":"Altuna-Coy","year":"2022","journal-title":"BMC Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev-pathol-020117-043617","article-title":"Recent insights into the pathogenesis of nonalcoholic fatty liver disease","volume":"13","author":"Arab","year":"2018","journal-title":"Annu. 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