{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:51:55Z","timestamp":1792612315448,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder characterized by hepatic lipid accumulation and gut microbiota dysbiosis.\n                      <jats:italic>Schisandra chinensis (Turcz.) Baill.<\/jats:italic>\n                      (SCH), a traditional hepatoprotective herb, has shown therapeutic potential; however, its mechanisms in NAFLD remain incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the protective effects and underlying mechanisms of SCH against NAFLD through integrated genetic, experimental, and multi-omics approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mendelian randomization (MR) analysis based on large-scale genome-wide association study (GWAS) datasets was performed to evaluate the causal effects of lipid traits on NAFLD risk. An HFD-induced NAFLD mouse model was used to assess the therapeutic efficacy of SCH extract, with evaluations of serum lipid profiles, liver function, and histopathology. Multi-omics analyses\u2014including 16S rRNA sequencing, untargeted lipidomics, and hepatic metabolite profiling (LC-MS\/MS)\u2014were integrated with network pharmacology to predict active metabolite\u2013target\u2013pathway interactions.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , an FFA-induced HepG2 steatosis model was used to screen the bioactive fractions of SCH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SCH significantly reduced hepatic TG accumulation and improved serum lipid profiles. MR analysis confirmed TG as a causal factor for NAFLD. SCH intervention enriched beneficial taxa (e.g., Turicibacter, Muribaculaceae) while suppressing HFD-induced dysbiosis. Lipidomics revealed modulation of glycerophospholipid and choline metabolism. Key phytometabolites (e.g., schisandrin B, gomisin N) were correlated with microbial composition and lipid remodeling. Network pharmacology identified putative targets involved in lipid metabolism, inflammation, and neuroendocrine signaling (e.g., PTGS2, GABRA1, ESR1). GO and KEGG enrichment supported roles in oxidative stress, steroid hormone signaling, and GABAergic synapse pathways, consistent with experimental multi-omics results.\n                      <jats:italic>In vitro<\/jats:italic>\n                      assays demonstrated that the n-butanol (BuOH) fraction was the principal bioactive component, significantly reducing lipid accumulation in HepG2 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrative study demonstrates that SCH protects against NAFLD by lowering triglycerides, remodeling the gut\u2013liver axis, and reprogramming hepatic lipid metabolism. The BuOH fraction constitutes the main active component, supporting SCH as a promising multi-target candidate for NAFLD therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1715364","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:45:24Z","timestamp":1767599124000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Schisandra chinensis alleviates Hypertriglyceridemia in nonalcoholic fatty liver disease by modulating the gut microbiota and hepatic lipid metabolism: identification of its active fractions"],"prefix":"10.3389","volume":"16","author":[{"given":"Qi","family":"Li","sequence":"first","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Feng","sequence":"additional","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"luo","sequence":"additional","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen Yalin","family":"Ye","sequence":"additional","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ke","family":"Luo","sequence":"additional","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Xu","sequence":"additional","affiliation":[{"name":"Chengdu University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.chmed.2022.06.003","article-title":"Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR\/LXR-mediated P2X7R\/NLRP3\/NF-kappaB pathway activation","volume":"14","author":"Bao","year":"2022","journal-title":"Chin. 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