{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:04Z","timestamp":1787029204374,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project of the Discipline Innovation and Talent Introduction Plan for Colleges and Universities of the Ministry of Education and the Ministry of Science and Technology of China","award":["B20055"],"award-info":[{"award-number":["B20055"]}]},{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine","award":["201212"],"award-info":[{"award-number":["201212"]}]},{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine","award":["BZ0259"],"award-info":[{"award-number":["BZ0259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Erhuang Quzhi Formula (EQF) has been used for the treatment of non-alcoholic fatty liver disease (NAFLD). However, its active components and mechanistic basis remain unclear. This study aims to systematically identify the therapeutic material basis of EQF and to elucidate its potential mechanisms of action against NAFLD through an integrated multi-omics strategy. Methods: An integrated strategy combining UPLC-Q-TOF-MS and network pharmacology was applied to characterize serum components of EQF and construct a compound\u2013target network. Core targets were screened and validated by molecular docking. A NAFLD model was established in C57BL\/6 mice through high-fat diet feeding. To evaluate the therapeutic effects, mice were treated with EQF and assessed by measurements of serum biochemical parameters, liver histopathology, and glucose tolerance. UPLC-Q-TOF-based lipidomic and metabolomic analyses of liver tissue were conducted to clarify EQF\u2019s regulatory effects on global lipid profiles and endogenous metabolites. Key genes and proteins involved in relevant signaling pathways were verified by RT-qPCR and Western blot. Results: A total of thirty-one prototype compounds were identified in the EQF-containing serum. Network pharmacology analysis predicted that EQF may alleviate NAFLD by acting on core targets such as TNF, JUN, and STAT3. In vivo experiments demonstrated that EQF administration significantly improved liver function, attenuated dyslipidemia, and reduced inflammation in model mice. Furthermore, metabolomic and lipidomic analyses indicated that EQF effectively reversed abnormal glycerophospholipid and sphingolipid levels and restored their metabolic homeostasis. Conclusions: EQF exerts therapeutic effects in a NAFLD mouse model through multi-component, multi-target, and multi-pathway mechanisms, primarily associated with the regulation of lipid metabolism, improvement of liver function, and suppression of inflammatory responses. This study provides mechanistic insights and a pharmacodynamic basis for the future clinical investigation of EQF.<\/jats:p>","DOI":"10.3390\/nu17243849","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:22:40Z","timestamp":1765376560000},"page":"3849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Multi-Omics Study Reveals the Active Components and Therapeutic Mechanism of Erhuang Quzhi Formula for Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Teng","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome and Guangdong Provincial Key Laboratory of Syndrome and Formula, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, Hengqin, Zhuhai 519000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zipeng","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-4735","authenticated-orcid":false,"given":"Dongmei","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Health Cultivation of Traditional Chinese Medicine, The Ministry of Education, The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1146\/annurev-med-042220-020407","article-title":"Fatty Liver Disease: Diagnosis and Stratification","volume":"73","author":"Saiman","year":"2022","journal-title":"Annu. 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