{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:21:33Z","timestamp":1788787293799,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82405155"],"award-info":[{"award-number":["82405155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81302768"],"award-info":[{"award-number":["81302768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270435"],"award-info":[{"award-number":["82270435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is a highly prevalent chronic liver condition globally, closely linked to disrupted lipid metabolism, yet effective targeted therapies remain elusive. While we previously reported the efficacy of ShuGan\u2010QieZhi Capsule against fatty liver disease, the therapeutic potential of its active component, Neohesperidin (NH), in MASLD was unknown. Here, we demonstrate that NH effectively alleviates lipid accumulation in high\u2010fat diet (HFD)\u2010induced mice and palmitic acid (PA)\u2010treated hepatocytes. Mechanistically, NH directly binds to PHE248 of ECHS1, a key enzyme in fatty acid \u03b2\u2010oxidation, and inhibits its ubiquitin\u2010proteasome\u2010mediated degradation, thereby stabilizing ECHS1 and promoting lipid catabolism. Additionally, NH modulates the PPAR\u03b1 signaling pathway, contributing to its overall therapeutic effect. Our findings not only identify ECHS1 as a promising therapeutic target for MASLD but also propose NH as a first\u2010in\u2010class small molecule that directly stabilizes ECHS1, providing a novel strategy against MASLD by targeting protein stability to restore lipid homeostasis.<\/jats:p>","DOI":"10.1002\/ptr.70400","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:16:16Z","timestamp":1782731776000},"page":"5585-5600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neohesperidin Regulates Lipid Metabolism and Ameliorates\n                    <scp>MASLD<\/scp>\n                    by Targeting\n                    <scp>ECHS1<\/scp>"],"prefix":"10.1002","volume":"40","author":[{"given":"Hongyan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1336-7456","authenticated-orcid":false,"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-7354","authenticated-orcid":false,"given":"Xisong","family":"Ke","sequence":"additional","affiliation":[{"name":"Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-1015","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217061"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2024.101185"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136518"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/00368504211011344"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.10.042"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32751-5"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-025-03959-y"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154813"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.135"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(24)00193-6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0319049"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/15330338221140655"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00381-6"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00759-2"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.4597"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.01.016"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0239"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2840"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62731-9"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-025-02720-5"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910040106"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.88604"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233606"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1567573"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323323"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.02.033"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-024-09523-3"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41387-020-00130-3"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1093"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c03574"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110319"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-025-00459-9"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23486"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155173"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:07:20Z","timestamp":1788786440000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ptr.70400"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70400","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"2026-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}