{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:12:05Z","timestamp":1790187125968,"version":"4.1.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"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><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Phlomoides rotata<\/jats:italic> (Benth. ex Hook.f.) Mathiesen (syn. <jats:italic>Lamiophlomis rotata<\/jats:italic> (Benth. ex Hook.f.) Kud\u00f4) (<jats:italic>P. rotate<\/jats:italic>) is a traditional Tibetan medicine known for its hemostatic, analgesic, and anti-inflammatory effects, as well as its high content of 8-<jats:italic>O<\/jats:italic>-Acetyl Shanzhiside methyl ester (8-<jats:italic>O<\/jats:italic>aS). Clinical and experimental studies have reported gastrointestinal side effects, such as diarrhea, loose stools, even to black stools, associated with <jats:italic>P. rotata<\/jats:italic>. Given the bitter taste characteristic, laxative and antipyretic effects of iridoid glycosides, this study aims to investigate the antipyretic and anti-inflammatory effects of 8-<jats:italic>O<\/jats:italic>aS (the primary iridoid glycosides of <jats:italic>P. rotate<\/jats:italic>) on yeast-induced pyrexia in rats. Additionally, the role 8-<jats:italic>O<\/jats:italic>aS in modulating the intestinal flora composition and metabolome profile is explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The pyretic rat model was established by injected subcutaneously with 20% dry yeast suspension. Serum, hypothalamic tissues and colon content were collected for the assessment of relevant indicators. The peripheral inflammatory factors and central thermoregulatory mediators were assessed using enzyme-linked immunosorbent assay (ELISA). The expressions of mRNA and protein in hypothalamic tissue were evaluated through polymerase chain reaction (PCR), immunohistochemistry, and western blotting. 16S rDNA sequencing and LC-MS\/MS were performed to determine the alteration and correlation of the intestinal flora and neurotransmitters in the colonic contents and hypothalamus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion:<\/jats:title><jats:p>Results show that 8-<jats:italic>O<\/jats:italic>aS treatment reduced pyrogenic cytokines (such as IL-6, IL-1\u03b2), and down-regulated the level of central thermoregulatory mediators (PGE<jats:sub>2<\/jats:sub>), via multiply involved in TLR4\/NF-\u03baB and HSP70\/NF-\u03baB signaling pathways. Crucially, 8-<jats:italic>O<\/jats:italic>aS treatment significantly reduced the relative abundance of <jats:italic>Alistipes <\/jats:italic>(<jats:italic>P<\/jats:italic> &amp;lt; 0.01), <jats:italic>Odoribacter<\/jats:italic> (<jats:italic>P<\/jats:italic> &amp;lt; 0.05) and <jats:italic>Alistipes_finegoldii<\/jats:italic> (<jats:italic>P<\/jats:italic> &amp;lt; 0.05) in the intestinal flora. The correlation analysis demonstrated that 8-<jats:italic>O<\/jats:italic>aS treatment significantly correlated with the increasing on the abundance of <jats:italic>Alistipes<\/jats:italic> and levels of 5-hydroxytryptamine (<jats:italic>P<\/jats:italic> &amp;lt; 0.01), and tryptamine (<jats:italic>P<\/jats:italic> &amp;lt; 0.01). Our findings indicate that 8-<jats:italic>O<\/jats:italic>aS exhibits significant antipyretic and anti-inflammatory properties, potentially mediated by intestinal flora and metabolites of neurotransmitters. The results of this study may help to elucidate the antipyretic and anti-inflammatory mechanism of 8-<jats:italic>O<\/jats:italic>aS based on intestinal flora and metabolomics analysis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1482323","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:29:53Z","timestamp":1745818193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Elucidation of the antipyretic and anti-inflammatory effect of 8-O-Acetyl Shanzhiside methyl ester based on intestinal flora and metabolomics analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaolin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3164\/jcbn.15-152","article-title":"Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population","volume":"59","author":"Andoh","year":"2016","journal-title":"J. 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