{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:41:27Z","timestamp":1791477687800,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016804","name":"Natural Science Foundation of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20230807150911023"],"award-info":[{"award-number":["JCYJ20230807150911023"]}],"id":[{"id":"10.13039\/100016804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016804","name":"Natural Science Foundation of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20240813165130040"],"award-info":[{"award-number":["JCYJ20240813165130040"]}],"id":[{"id":"10.13039\/100016804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Jiuwei Xiaozhi Decoction (JWXZ) is a nine\u2010herb traditional Chinese medicine formula clinically used for hepatic steatosis and dyslipidemia, but its chemical basis and pharmacological mechanisms in metabolic dysfunction\u2010associated steatotic liver disease (MASLD) remain incompletely defined. The chemical profile of JWXZ was characterized by UHPLC\u2010HRMS\/MS. Its therapeutic effects were evaluated in a high\u2010fat diet (HFD)\u2010induced mouse model of MASLD, followed by hepatic transcriptomic analysis, network pharmacology, molecular docking, Western blotting, and immunofluorescence validation. UHPLC\u2010HRMS\/MS identified 178 chemical constituents in JWXZ, including phenolic acids, flavonoids, flavonoid glycosides, alkaloids, isoflavones, and coumarins. In HFD\u2010fed mice, JWXZ attenuated body weight gain, white adipose accumulation, dyslipidemia, hepatic triglyceride and cholesterol accumulation, serum transaminase elevation, and hepatic steatosis, while improving glucose tolerance and partially restoring whole\u2010body metabolic flexibility. Hepatic transcriptomics identified 124 HFD\u2010dysregulated genes reversed by high\u2010dose JWXZ, with prominent enrichment in cholesterol and sterol biosynthesis, endoplasmic reticulum proteostasis, oxidative stress response, and PPAR\u03b1\u2010related lipid handling. Integrated transcriptomic and network pharmacology analyses further identified 157 shared targets and 18 overlapping pathways, converging mainly on cholesterol metabolism and PPAR signaling. Protein\u2010level validation showed that JWXZ suppressed SREBP2 proteolytic activation, reduced nuclear SREBP2 abundance, and downregulated HMGCR, SQLE, and PCSK9, indicating inhibition of the hepatic cholesterogenic program. In parallel, JWXZ restored nuclear PPAR\u03b1 abundance and CPT1A expression, consistent with reactivation of fatty acid oxidation. JWXZ also reduced hepatic EGFR phosphorylation and lowered hepatic and circulating TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2, and MCP\u20101 levels. Molecular docking provided supportive evidence for potential interactions between representative JWXZ constituents and key regulators, including naringin\u2010HMGCR, chlorogenic acid\u2010SQLE, rhoifolin\u2010PPAR\u03b1, and rhoifolin\u2010SREBP2. These findings suggest that JWXZ ameliorates HFD\u2010induced MASLD mainly by rebalancing hepatic lipid metabolism through coordinated suppression of SREBP2\u2010mediated cholesterogenesis and restoration of PPAR\u03b1\u2010mediated fatty acid oxidation, with associated attenuation of EGFR\u2010linked inflammatory responses.<\/jats:p>","DOI":"10.1111\/cbdd.70371","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:18:42Z","timestamp":1785302322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Jiuwei Xiaozhi Decoction Alleviates High\u2010Fat Diet\u2010Induced\n                    <scp>MASLD<\/scp>\n                    by Suppressing Hepatic\n                    <scp>SREBP2<\/scp>\n                    \u2010Driven Cholesterogenesis and Restoring\n                    <scp>PPAR\u03b1<\/scp>\n                    \u2010Mediated Fatty Acid Oxidation"],"prefix":"10.1111","volume":"108","author":[{"given":"Youcheng","family":"Ma","sequence":"first","affiliation":[{"name":"Shenzhen Hospital Beijing University of Chinese Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Gao","sequence":"additional","affiliation":[{"name":"National Institute of TCM Constitution and Preventive Medicine Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-8220","authenticated-orcid":false,"given":"Ji","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of TCM Constitution and Preventive Medicine Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingru","family":"Li","sequence":"additional","affiliation":[{"name":"National Institute of TCM Constitution and Preventive Medicine Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4712-2781","authenticated-orcid":false,"given":"Zhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital Beijing University of Chinese Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7839-5151","authenticated-orcid":false,"given":"Fangli","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital Beijing University of Chinese Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12263\u2010015\u20100495\u2010x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01690-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-025-00626-y"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2024.101185"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021109"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15121740"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210828"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010024\u201006196\u20103"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12051122"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1709791"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309000"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.034"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1007274"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01307-5"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2024.106308"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2026.118460"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci198334"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030673"},{"issue":"5","key":"e_1_2_12_20_1","first-page":"37","article-title":"Lecture 23: Discussion on Medical Cases of Fatty Liver","volume":"14","author":"Li Y. 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