{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:52:09Z","timestamp":1790855529210,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study explores hyperoside\u2019s therapeutic efficacy in non-alcoholic fatty liver disease (NAFLD) rats and its gut\u2013liver axis mechanisms through integrated gut microbiota and metabolomics analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The SD rats were divided into five groups (normal control, NAFLD model, low-dose hyperoside [0.6\u2009mg\/kg\/day], high-dose hyperoside [1.5\u2009mg\/kg\/day], and rosiglitazone positive control [5\u2009mg\/kg\/day]) and treated for 12\u2009weeks. Body weight, serum biochemistry (ALT, AST, TC, TG), liver histopathology (H&amp;amp;E, Sirius Red), hepatic mRNA expression (\n                      <jats:italic>Tlr4, Tnf-\u03b1,<\/jats:italic>\n                      and\n                      <jats:italic>\u03b1-SMA<\/jats:italic>\n                      ), gut microbiota (16S rRNA sequencing), and serum metabolites (untargeted metabolomics) were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hyperoside dose-dependently reduced high-fat, high-sugar diet-induced body weight gain, liver index, and hepatic steatosis\/fibrosis, lowered serum liver enzymes and lipid levels, and downregulated pro-inflammatory\/fibrotic genes. It remodeled gut microbiota by enriching Lactobacillus and suppressing pathobionts (e.g.,\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      ,\n                      <jats:italic>Escherichia-Shigella<\/jats:italic>\n                      ), reversed metabolic disturbances (e.g., 3-hydroxybutyric acid, diacylglycerols), and targeted glycine\/serine\/threonine and alpha-linolenic acid metabolism. Beneficial bacteria were negatively correlated with pro-inflammatory metabolites like lysophosphatidylcholine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hyperoside ameliorates NAFLD, which is associated with gut microbiota remodeling and modulation of host metabolic networks, supporting its potential as a multi-target therapeutic agent for NAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2025.1741026","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:39:57Z","timestamp":1768196397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hyperoside ameliorates NAFLD in rats via remodeling gut microbiota and reprogramming serum metabolic networks"],"prefix":"10.3389","volume":"12","author":[{"given":"Mingchun","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12902-022-00980-1","article-title":"Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss","volume":"22","author":"Pouwels","year":"2022","journal-title":"BMC Endocr 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