{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:49:12Z","timestamp":1776235752829,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to investigate the therapeutic mechanism of red yeast rice extract (RYRE) in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through untargeted metabolomics analysis and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An untargeted metabolomics analysis based on UHPLC-QTOF\/MS was performed to identify differential metabolites in liver tissues. A NAFLD model was established in hamsters by HFD feeding. Forty hamsters were randomly allocated into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f10 per group): control (CON), model (MOD), red yeast rice extract (Xuezhikang, XZK), and simvastatin (SVT). Serum levels of lipids (TG, CHO, HDL-C, LDL-C), liver function parameters (ALT, AST, ALB, ALP,\n                      <jats:italic>\u03b3<\/jats:italic>\n                      -GT, TBiL, DBiL, TBA), and inflammatory cytokines (TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , IL-4, IL-1\n                      <jats:italic>\u03b2<\/jats:italic>\n                      , TGF-\u03b2) were measured by biochemical assays and ELISA. Liver tissues were subjected to Oil Red O, hematoxylin\u2013eosin (HE), and Masson staining for histopathological evaluation. Additionally, qPCR and immunohistochemistry were employed to investigate the underlying signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      XZK significantly reduced serum levels of DBiL, TBiL, TBA, CHO, TG, and LDL-C, while increasing HDL-C in HFD-fed hamsters. Both XZK and SVT markedly decreased pro-inflammatory cytokines. Untargeted metabolomics identified 135 differential metabolites between the MOD and XZK groups (83 down-regulated, 52 up-regulated), which were primarily involved in carbon metabolism, lipid metabolism, and hormone metabolism. Mechanistically, XZK attenuated the JNK\/AP-1\/TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      signaling pathway, as evidenced by reduced mRNA expression of cFos, cJUN, JAK1\/2\/3, and TNF-\u03b1, along with decreased protein levels of p-JNK, cFos, cJUN, and TNF-\u03b1. Notably, the p-cJun\/total cJun ratio showed a distinct regulatory pattern, suggesting complex modulation of AP-1 subunit phosphorylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      XZK effectively ameliorates hepatic steatosis, dyslipidemia, and inflammation in HFD-induced NAFLD hamsters. The therapeutic effects are mediated through restoration of metabolic homeostasis and suppression of the JNK\/AP-1\/TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1771594","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:46:44Z","timestamp":1776232004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Red yeast rice extract\u2019s impact on liver health: a pharmacological and metabolomic exploration"],"prefix":"10.3389","volume":"13","author":[{"given":"Mo","family":"Zhao","sequence":"first","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]},{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Service Department of the Guard Bureau of the Joint Staff Department","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingdong","family":"Lu","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zucheng","family":"Shang","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimei","family":"Lu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoli","family":"Wang","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzheng","family":"Li","sequence":"additional","affiliation":[{"name":"Guang\u2019an Men Hospital, China Academy of Chinese Medical Science","place":["Beijing, China"]},{"name":"Faculty of Medicine, University of British 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