{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:51:14Z","timestamp":1790182274615,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013061","name":"Jilin Provincial Scientific and Technological Development Program","doi-asserted-by":"publisher","award":["20200404138YY"],"award-info":[{"award-number":["20200404138YY"]}],"id":[{"id":"10.13039\/501100013061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The sedative and hypnotic properties of 5,7,3\u2032,4\u2032,5\u2032\u2010pentamethoxyflavone (PMF), a monomer extracted from the leaves of <jats:italic>Murraya paniculata<\/jats:italic> (L.) Jack, have been reported. However, the role of PMFs in the development of anxiety remains uncertain. An anxiety model was developed using chronic unpredictable mild stimulation (CUMS). Kunming mice were randomly allocated to the following groups: control, CUMS, PMF (50\u2009mg\/kg), PMF (100\u2009mg\/kg), and diazepam (3\u2009mg\/kg). The anxiolytic effects of PMFs were evaluated using elevated plus maze (EPM) test and open field test (OFT). Enzyme\u2010linked immunosorbent assay (ELISA) kits were used to analyze the serum levels of corticosterone (CORT), 5\u2010hydroxytryptamine (5\u2010HT), gamma\u2010aminobutyric acid (GABA), and cyclic adenosine monophosphate (cAMP) in the hippocampus. High\u2010throughput\u201016S rRNA sequencing was performed to investigate its effect on the composition of the gut microbiota. Subsequently, western blotting was performed to assess the expression of GABAergic synaptic\u2010associated proteins. PMF effectively mitigated CUMS\u2010induced anxiety\u2010like behavior. Further examination revealed that PMF treatment ameliorated dysfunction of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and increased 5\u2010HT and GABA levels in the hippocampus. Notably, the ability of PMF to maintain the stability of GABAergic synapses by enhancing the species composition of the gut microbiota and acting on the adenosine a2a receptor (A<jats:sub>2A<\/jats:sub>R)\/gephyrin\/gamma\u2010aminobutyric acid A receptor alpha 2 (GABRA2) pathway revealed a previously unrecognized mechanism for the anxiolytic effect of PMF. These findings suggest that PMF enhances the expression of A<jats:sub>2A<\/jats:sub>R, preserves GABAergic synaptic stability, and reduces anxiety by modulating the microbiota composition. Thus, it holds promise as an anxiolytic agent.<\/jats:p>","DOI":"10.1002\/ptr.8327","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:59:00Z","timestamp":1726102740000},"page":"5539-5548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["5,7,3\u2032,4\u2032,5\u2032\u2010Pentamethoxyflavone, a Flavonoid Monomer Extracted From <i>Murraya paniculata<\/i> (L.) Jack, Alleviates Anxiety Through the <scp>A<sub>2A<\/sub>R<\/scp>\/Gephyrin\/<scp>GABRA2<\/scp> Pathway"],"prefix":"10.1002","volume":"38","author":[{"given":"Wenli","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayun","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences Jilin 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