{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:10:16Z","timestamp":1792123816027,"version":"4.4.0"},"reference-count":50,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Metabolic dysfunction-associated steatosic liver disease (MASLD) poses a global health challenge with limited therapeutic options. Hesperetin, a flavonoid extracted from citrus, exhibits multiple pharmacological properties, but its mechanisms in MASLD-associated lipid metabolism remain unclear. This study aimed to explore the mechanism of hesperetin for treating MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Network pharmacology identified the therapeutic targets for MASLD. Key targets were selected based on network topology analysis. Subsequently, Kyoto Encyclopedia of genes and genomes (KEGG) pathways and gene ontology enrichment were conducted. Molecular docking was performed to evaluate the binding affinity between hesperetin and the identified key targets.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation included lipid accumulation assays and verification of core target modulation\n                      <jats:italic>via<\/jats:italic>\n                      western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hesperetin significantly attenuated lipid accumulation in free fatty acid -induced HepG2 cells. Forty core targets of hesperetin for MASLD mitigation were identified. Notably, MYC, IL-6, IL1B, and PTGS2 had high network association values. KEGG analysis revealed predominant involvement in cancer-related pathways, non-alcoholic fatty liver disease, and JAK\/STAT signaling. Biological processes included inflammatory response regulation and cytokine activity. Molecular docking confirmed strong hesperetin-IL-6 binding. Experimental data suggested that hesperetin may ameliorate lipid accumulation by modulating the IL-6-mediated STAT3-SOCS3 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hesperetin may ameliorate MASLD by targeting the IL-6-STAT3-SOCS3 axis, underscoring its therapeutic potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2025-1215","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T10:56:07Z","timestamp":1749466567000},"source":"Crossref","is-referenced-by-count":10,"title":["Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease\n                    <i>via<\/i>\n                    network pharmacology and\n                    <i>in vitro<\/i>\n                    experiments"],"prefix":"10.1515","volume":"20","author":[{"given":"Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , No. 68. Gehu Middle Road , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second People\u2019s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University , Changzhou , Jiangsu, 213164 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"2025122201304115587_j_med-2025-1215_ref_001","doi-asserted-by":"crossref","unstructured":"Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. 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