{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:58:10Z","timestamp":1793116690282,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20240340"],"award-info":[{"award-number":["BK20240340"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007131","name":"Changzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["CJ20240044"],"award-info":[{"award-number":["CJ20240044"]}],"id":[{"id":"10.13039\/501100007131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Ischemic stroke (IS) is the most common type of stroke, known for its high rates of morbidity, disability, mortality, and recurrence. Polygoni Multiflori Radix Praeparata (PM), a traditional Chinese medicinal tonic, is frequently used for treating IS. Its polysaccharides (PMP) are acknowledged for their hepatoprotective, immunomodulatory, and neuroprotective properties. However, the effectiveness and mechanisms of PMP remain inadequately understood. This study seeks to evaluate the impact of PMP on IS and clarify the potential mechanisms involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PMP was obtained by water extraction, alcohol precipitation, Sevage deproteinization, and dialysis. Its molecular weight, monosaccharide composition, and FT-IR spectrum were characterized. IS was established by middle cerebral artery occlusion\/reperfusion (MCAO\/R) in male SD rats. Neurological assessment, histopathology, and protein factors detection assessed PMP\u2019s effectiveness. Further, <jats:sup>1<\/jats:sup>H NMR based metabolomics and 16S rRNA gene sequencing examined gut microbiota metabolites and profiles, respectively, in order to elucidate the underlying mechanisms from the perspective of the gut-brain axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PMP significantly improved the neurologic functions and reduced the cerebral infarction volume in MCAO\/R rats. Cerebral ischemia\/reperfusion (I\/R) injured brain and also affected intestine, leading to gut barrier disruption. PMP could lower the levels of inflammatory cytokines, such as TNF-\u03b1 and IL-1\u03b2, and boost tight junction protein both in brain and intestinal tissues. Metabolomic analysis shows PMP raised intestinal levels of SCFAs (butyrate, propionate) and beneficial amino acids, thus improving disrupted carbohydrate and amino acid metabolism. 16S rRNA gene sequencing revealed that the abundance of <jats:italic>Bifidobacterium<\/jats:italic>, <jats:italic>Muribaculaceae<\/jats:italic>, and <jats:italic>Lactobacillus<\/jats:italic> was reversed after PMP intervention. The family <jats:italic>Bacteroidaceae<\/jats:italic> and the genus <jats:italic>Bacteroides<\/jats:italic> correlated positively with amino acids, and might contributed to the SCFAs production. While the family <jats:italic>Peptostreptococcaceae<\/jats:italic> and the <jats:italic>genus Romboutsia<\/jats:italic> correlated negatively with SCFAs, might related to the poor prognosis of IS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PMP markedly enhanced SCFAs and amino acid metabolism, as well as the proliferation of beneficial gut microbiota, thereby promoting intestinal health and barrier integrity, and thus relieving MCAO\/R induced I\/R injury both in brain and intestine. Our study substantiates the potential of PMP as a prebiotic health supplement in clinical settings for the prevention and treatment of IS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1580055","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T08:56:55Z","timestamp":1747904215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Polygoni Multiflori Radix Praeparata polysaccharides enhance gut health and mitigate ischemic stroke by regulating SCFA and amino acid metabolism in gut microbiota"],"prefix":"10.3389","volume":"16","author":[{"given":"Lingyu","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhennan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3389\/fimmu.2018.00363","article-title":"NLRX1 modulates immunometabolic mechanisms controlling the host\u2013gut microbiota interactions during inflammatory bowel disease","volume":"9","author":"Andrew","year":"2018","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e3438","DOI":"10.21769\/BioProtoc.3438","article-title":"Intra-arterial drug delivery to the ischemic brain in rat middle cerebral artery occlusion model","volume":"9","author":"Azedi","year":"2019","journal-title":"Bio-protocol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.3390\/nu10101499","article-title":"Impact of diet-modulated butyrate production on intestinal barrier function and inflammation","volume":"10","author":"Bach Knudsen","year":"2018","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"111837","DOI":"10.1016\/j.jep.2019.111837","article-title":"Effect of Pei Yuan Tong Nao capsules on neuronal function and metabolism in cerebral ischemic rats","volume":"238","author":"Bai","year":"","journal-title":"J. Ethnopharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"36","DOI":"10.4103\/wjtcm.wjtcm_8_19","article-title":"Effects of peiyuan Tongnao capsule on working memory and the expression of glutamic acid and receptor in hippocampal area in rats with cerebral ischemia","volume":"5","author":"Bai","year":"","journal-title":"World J. Tradit. Chin. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0381522","DOI":"10.1128\/spectrum.03815-22","article-title":"Amylopectin partially substituted by cellulose in the hindgut was beneficial to short-chain fatty acid production and probiotic colonization","volume":"11","author":"Bai","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1365-2222.2009.03383.x","article-title":"Interleukin-13: prospects for new treatments","volume":"40","author":"Brightling","year":"2010","journal-title":"Clin. Exp. allergy"},{"key":"B8","doi-asserted-by":"publisher","first-page":"862763","DOI":"10.3389\/fphar.2022.862763","article-title":"Codonopsis pilosula polysaccharide improved spleen deficiency in mice by modulating gut microbiota and energy related metabolisms","volume":"13","author":"Cao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"7929","DOI":"10.1080\/10408398.2021.1920884","article-title":"Short-chain fatty acids-producing probiotics: a novel source of psychobiotics","volume":"62","author":"Cheng","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B10","first-page":"425","article-title":"Microbiome\u2013gut\u2013brain Axis","volume-title":"Encyclopedia of Metagenomics","author":"Clarke","year":"2015"},{"key":"B11","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"125953","DOI":"10.1016\/j.ijbiomac.2023.125953","article-title":"Poria cocos polysaccharide improves intestinal barrier function and maintains intestinal homeostasis in mice","volume":"249","author":"Duan","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13293-020-00352-1","article-title":"Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats","volume":"12","author":"El-Hakim","year":"2021","journal-title":"Biol. Sex. Differ."},{"key":"B14","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.3389\/fphar.2018.01354","article-title":"Gut microbiota, short-chain fatty acids, and herbal medicines","volume":"9","author":"Feng","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2202\/1557-4679.1065","article-title":"The Benjamini-Hochberg method in the case of discrete test statistics","volume":"3","author":"Ferreira","year":"2007","journal-title":"Int. J. Biostat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.3390\/molecules13081599","article-title":"Composition and applications of Aloe vera leaf gel","volume":"13","author":"Hamman","year":"2008","journal-title":"Molecules"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e143777","DOI":"10.1172\/JCI143777","article-title":"Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury","volume":"131","author":"Hanscom","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1159\/000481519","article-title":"Gut microbiota-dependent modulation of energy metabolism","volume":"10","author":"Heiss","year":"2018","journal-title":"J. Innate. Immun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1080\/19490976.2017.1290756","article-title":"Dietary fiber and prebiotics and the gastrointestinal microbiota","volume":"8","author":"Holscher","year":"2017","journal-title":"Gut Microbes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4937","DOI":"10.1007\/s10072-021-05603-6","article-title":"Influence of the gut microbiome on inflammatory and immune response after stroke","volume":"42","author":"Huang","year":"2021","journal-title":"Neurol. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1021\/acs.jafc.1c05966","article-title":"Protective effects of natural polysaccharides on intestinal barrier injury: a review","volume":"70","author":"Huo","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40168-021-01007-y","article-title":"Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis","volume":"9","author":"Jing","year":"2021","journal-title":"Microbiome"},{"key":"B24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S1474-4422(09)70266-2","article-title":"Medical complications after stroke","volume":"9","author":"Kumar","year":"2010","journal-title":"Lancet Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1161\/CIRCRESAHA.119.316448","article-title":"Gut microbiota\u2013derived short-chain fatty acids promote poststroke recovery in aged mice","volume":"127","author":"Lee","year":"2020","journal-title":"Circ. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1089\/jmf.2018.4394","article-title":"Polysaccharide from the Seeds of Plantago asiatica L. Protect against lipopolysaccharide-induced liver injury","volume":"22","author":"Li","year":"2019","journal-title":"J. Med. Food"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e02897","DOI":"10.1016\/j.heliyon.2019.e02897","article-title":"The experimental research on neuroplasticity in rats\u2019 hippocampus subjected to chronic cerebral hypoperfusion and interfered by Modified Dioscorea Pills","volume":"6","author":"Li","year":"2020","journal-title":"Heliyon"},{"key":"B28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jpba.2018.03.049","article-title":"Protective effects of Polygonum multiflorum on ischemic stroke rat model analysed by 1H NMR metabolic profiling","volume":"155","author":"Li","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1461177","DOI":"10.3389\/fphar.2025.1461177","article-title":"Ginseng and Polygonum multiflorum formula protects brain function in Alzheimer\u2019s disease","volume":"16","author":"Liu","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"B31","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrmicro3344","article-title":"The gut microbiota, bacterial metabolites and colorectal cancer","volume":"12","author":"Louis","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"115719","DOI":"10.1016\/j.jpba.2023.115719","article-title":"Maintaining immune homeostasis with Coptis Chinensis water extract to mitigate sepsis severity via modulating gut microbiome and metabolism","volume":"236","author":"Meng","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1097\/01.WCB.0000130867.32663.90","article-title":"Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke","volume":"24","author":"O\u2019Donnell","year":"2004","journal-title":"J. Cerebr. Blood F. Met."},{"key":"B35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40168-016-0181-2","article-title":"Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals","volume":"4","author":"Ormerod","year":"2016","journal-title":"Microbiome"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12602-024-10256-w","article-title":"Cell-free supernatant of Lactobacillus rhamnosus and Bifidobacterium breve ameliorates ischemic stroke-generated neurological deficits in rats","author":"Rahman","year":"2024","journal-title":"Probiotics and Antimicro. Prot."},{"key":"B37","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1103836","DOI":"10.3389\/fmicb.2022.1103836","article-title":"Butyrate producers, \u201cThe Sentinel of Gut\u201d: their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics","volume":"13","author":"Singh","year":"2022","journal-title":"Front. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1038\/jcbfm.2014.130","article-title":"Neurogenesis and inflammation after ischemic stroke: what is known and where we go from here","volume":"34","author":"Tobin","year":"2014","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1136\/gutjnl-2018-317571","article-title":"Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis","volume":"68","author":"Van der Post","year":"2019","journal-title":"Gut"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1039\/c7fo01507k","article-title":"The effect of probiotics and polysaccharides on the gut microbiota composition and function of weaned rats","volume":"9","author":"Wang","year":"2018","journal-title":"Food Funct."},{"key":"B42","doi-asserted-by":"publisher","first-page":"587284","DOI":"10.10.3389\/fcimb.2020.587284","article-title":"Gut microbiotic features aiding the diagnosis of Acute ischemic stroke","volume":"21","author":"Xiang","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.1080\/10408398.2015.1069255","article-title":"Advances on bioactive polysaccharides from medicinal plants","volume":"56","author":"Xie","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1136\/gutjnl-2020-323263","article-title":"Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn","volume":"70","author":"Xu","year":"2021","journal-title":"Gut"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.2174\/0929867321666131228205146","article-title":"Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets","volume":"21","author":"Yenari","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e002699","DOI":"10.1161\/JAHA.115.002699","article-title":"Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack","volume":"4","author":"Yin","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"B47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s40168-023-01491-4","article-title":"Endogenous small intestinal microbiome determinants of transient colonisation efficiency by bacteria from fermented dairy products: a randomised controlled trial","volume":"11","author":"Zaccaria","year":"2023","journal-title":"Microbiome"},{"key":"B48","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.jare.2024.02.020","article-title":"Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3\/\u03b2-catenin signalling pathway","volume":"68","author":"Zhang","year":"2025","journal-title":"J. Adv. Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1177\/0271678X20910533","article-title":"Sodium butyrate attenuated neuronal apoptosis via GPR41\/G\u03b2\u03b3\/PI3K\/Akt pathway after MCAO in rats","volume":"41","author":"Zhou","year":"2021","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1021\/acs.jafc.5b06103","article-title":"A polysaccharide from Ganoderma atrum improves liver function in type 2 diabetic rats via antioxidant action and short-chain fatty acids excretion","volume":"64","author":"Zhu","year":"2016","journal-title":"J. Agric. Food. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.3390\/nu16162660","article-title":"Exploration of the muribaculaceae family in the gut microbiota: diversity, metabolism, and function","volume":"16","author":"Zhu","year":"2024","journal-title":"Nutrients"}],"updated-by":[{"DOI":"10.3389\/fphar.2025.1636607","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000}}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1580055\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T08:48:18Z","timestamp":1750063698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1580055\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":51,"alternative-id":["10.3389\/fphar.2025.1580055"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1580055","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fphar.2025.1636607","asserted-by":"object"}]},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]},"article-number":"1580055"}}