{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:16Z","timestamp":1787027056390,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"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:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Non-alcoholic fatty liver disease (NAFLD) has gradually become the primary cause of fatty liver disease. Betel nuts have been used to treat gastrointestinal diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    In the present study, we analyzed the pathology, serology, gut flora, and metabolites in a rat model of NAFLD, with and without betel nut alkaloid treatment, using an integrated approach involving pathology, serological testing, 16S rRNA gene sequencing, and ultra-performance liquid chromatography-mass spectrometry metabolomics.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Two rats were used for model validation. Thirty SD rats were included and divided into the normal group (C group), NAFLD model group (M group), low-dose group, medium-dose group (T group), and high-dose group with intraperitoneal injection of arecoline. The expression of blood lipids was significantly downregulated at all three arecoline concentrations (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.05). Alpha-diversity analysis of the intestinal flora showed significant differences among the three groups, with a significant reduction in population diversity in the M group and a recovery of population diversity after arecoline treatment. At the phylum level, the relative abundance of\n                    <jats:italic>Firmicutes<\/jats:italic>\n                    was significantly higher in the T group and\n                    <jats:italic>Proteobacteria<\/jats:italic>\n                    in the M group. The KEGG metabolic pathways included polyketide sugar unit biosynthesis and hypertrophic cardiomyopathy. Thirty-three significantly different metabolites were identified among the groups. Significantly different metabolites between groups T and M included indolepyruvate, 2-deoxystreptamine, sakuranetin, glycyl-leucine, and riboflavin. The KEGG metabolic pathway suggested a potential role for arachidonic acid metabolism, serotonergic synapses, neuroactive ligand-receptor interactions, tyrosine metabolism, and regiomelanin. Vitamin digestion and absorption, as well as regulation of lipolysis in adipocytes, were the main metabolic pathways that distinguished the T vs. M groups. PGE2 is involved in several metabolic pathways. Correlation analysis showed that 29 bacterial species were significantly associated with PGE2 levels in the M and T groups.\n                    <jats:italic>Vagococcus<\/jats:italic>\n                    ,\n                    <jats:italic>Lawsonia<\/jats:italic>\n                    ,\n                    <jats:italic>Christensenella<\/jats:italic>\n                    , unidentified\n                    <jats:italic>Erysipelotrichaceae<\/jats:italic>\n                    , unidentified\n                    <jats:italic>Coriobacteriaceae<\/jats:italic>\n                    , and five other bacterial groups are unique in the PGE2 metabolic pathway regulated by arecoline.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    Arecoline has lipid-lowering effects and may exert therapeutic effects in NAFLD through intestinal metabolites and intestinal flora, as well as through the\n                    <jats:italic>Butyricicoccus<\/jats:italic>\n                    \/\n                    <jats:italic>Christensenella<\/jats:italic>\n                    \/\n                    <jats:italic>Coriobacteriaceae<\/jats:italic>\n                    -COX2\/PGE2 pathway. Thus, arecoline may represent a potential drug or target for NAFLD treatment.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1132026","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T01:08:49Z","timestamp":1679879329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut metabolomics and 16S rRNA sequencing analysis of the effects of arecoline on non-alcoholic fatty liver disease in rats"],"prefix":"10.3389","volume":"14","author":[{"given":"Lingping","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"32548","DOI":"10.1039\/d0ra05326k","article-title":"Metabolic characterisation of Magnetospirillum gryphiswaldense MSR-1 using LC-MS-based metabolite profiling","volume":"10","author":"Abdelrazig","year":"2020","journal-title":"RSC Adv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s12967-018-1619-z","article-title":"Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women","volume":"16","author":"Alem\u00e1n","year":"2018","journal-title":"J. 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