{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:40Z","timestamp":1787027560549,"version":"build-2736575974"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Spain)","award":["PID2020-116498RB-I00,"],"award-info":[{"award-number":["PID2020-116498RB-I00,"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Spain)","award":["CDTI -Center for Industrial Technological Development- project PID 2020-FEDER Funds"],"award-info":[{"award-number":["CDTI -Center for Industrial Technological Development- project PID 2020-FEDER Funds"]}]},{"name":"Centro de Investigaci\u00f3n en Red en Enfermedades Cardiovasculares","award":["CB16\/11\/00286"],"award-info":[{"award-number":["CB16\/11\/00286"]}]},{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["SI1-PJI-2019-00321"],"award-info":[{"award-number":["SI1-PJI-2019-00321"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen\u00ae (108 colony forming units\/day, 4 weeks). Prodefen\u00ae diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen\u00ae. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen\u00ae, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen\u00ae caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen\u00ae could be an interesting non-pharmacological approach to ameliorate hypertension.<\/jats:p>","DOI":"10.3390\/antiox11040680","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:22:14Z","timestamp":1648675334000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Supplementation with the Symbiotic Formulation Prodefen\u00ae Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats"],"prefix":"10.3390","volume":"11","author":[{"given":"Pablo","family":"M\u00e9ndez-Albi\u00f1ana","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Group of Chemistry and Functionality of Carbohydrates and Derivatives, Food Science Research Institute (CIAL) (CSIC-UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Mart\u00ednez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Camacho-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Ferreira-Lazarte","sequence":"additional","affiliation":[{"name":"Group of Chemistry and Functionality of Carbohydrates and Derivatives, Food Science Research Institute (CIAL) (CSIC-UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Villamiel","sequence":"additional","affiliation":[{"name":"Group of Chemistry and Functionality of Carbohydrates and Derivatives, Food Science Research Institute (CIAL) (CSIC-UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6348-1505","authenticated-orcid":false,"given":"Raquel","family":"Rodrigues-D\u00edez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Balfag\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-3320","authenticated-orcid":false,"given":"Ana B.","family":"Garc\u00eda-Redondo","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00aa Isabel","family":"Prieto-Nieto","sequence":"additional","affiliation":[{"name":"Research Institute University Hospital la Paz (IdIPaz), 28029 Madrid, Spain"},{"name":"Department of General and Digestive Surgery, Hospital Universitario la Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-2314","authenticated-orcid":false,"given":"Javier","family":"Blanco-Rivero","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Research Institute University Hospital la Paz (IdIPaz), 28029 Madrid, Spain"},{"name":"Center for Biomedical Research Network (CIBER) in Cardiovascular Diseases, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1097\/HJH.0000000000002021","article-title":"The global burden of hypertension exceeds 1.4 billion people: Should a systolic blood pressure target below 130 become the universal standard?","volume":"37","author":"Egan","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrcardio.2017.120","article-title":"Beyond gut feelings: How the gut microbiota regulates blood pressure","volume":"15","author":"Marques","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","unstructured":"(2018, May 24). World Health Organization. Available online: https:\/\/www.who.int\/es\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1161\/01.CIR.101.3.329","article-title":"Essential hypertension. Part I: Definition and etiology","volume":"101","author":"Carretero","year":"2000","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1161\/HYPERTENSIONAHA.116.06602","article-title":"Sex Differences in Hypertension: Recent Advances","volume":"68","author":"Gillis","year":"2016","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1093\/bja\/77.1.50","article-title":"Determinants of splanchnic blood flow","volume":"77","author":"Takala","year":"1996","journal-title":"Br. J. Anaesth."},{"key":"ref_7","first-page":"727","article-title":"Inervaci\u00f3n perivascular de la arteria mesent\u00e9rica superior: Implicaciones fisiopatol\u00f3gicas\u2014Perivascular innervation of the superior mesenteric artery: Pathophysiological implications","volume":"50","author":"Sastre","year":"2010","journal-title":"Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13484","DOI":"10.1111\/apha.13484","article-title":"Nitrergic perivascular innervation in health and diseases: Focus on vascular tone regulation","volume":"230","author":"Xavier","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.niox.2009.03.001","article-title":"Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications","volume":"20","author":"Zhou","year":"2009","journal-title":"Nitric Oxide"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/cs0990277","article-title":"Role of protein kinase C in electrical-stimulation-induced neuronal nitric oxide release in mesenteric arteries from hypertensive rats","volume":"99","author":"Ferrer","year":"2000","journal-title":"Clin. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/CS20080178","article-title":"Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation","volume":"117","author":"Xavier","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ll\u00e9venes, P., Rodrigues-D\u00edez, R., Cros-Bruns\u00f3, L., Prieto, M.I., Casan\u00ed, L., Balfag\u00f3n, G., and Blanco-Rivero, J. (2020). Beneficial Effect of a Multistrain Synbiotic Prodefen\u00ae Plus on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase, A. Nutrients, 12.","DOI":"10.3390\/nu12010117"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cros-Bruns\u00f3, L., Camacho-Rodr\u00edguez, L., Mart\u00ednez-Gonz\u00e1lez, \u00c1., Ll\u00e9venes, P., Salaices, M., Garc\u00eda-Redondo, A.B., and Blanco-Rivero, J. (2021). A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020570"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/hr.2010.201","article-title":"Reactive oxygen species and vascular biology: Implications in human hypertension","volume":"34","author":"Touyz","year":"2011","journal-title":"Hypertens. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1097\/HJH.0b013e32835f749c","article-title":"Aerobic exercise training increases neuronal nitric oxide release and bioavailability and decreases noradrenaline release in mesenteric artery from spontaneously hypertensive rats","volume":"31","author":"Roque","year":"2013","journal-title":"J. Hypertens."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/cvr\/cvp107","article-title":"Nrf2-dependent upregulation of antioxidative enzymes: A novel pathway for proteasome inhibitor-mediated cardioprotection","volume":"83","author":"Dreger","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1042\/CS20150436","article-title":"Nrf2 in health and disease: Current and future clinical implications","volume":"129","author":"Clarner","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_18","first-page":"S1","article-title":"Nrf2 as a key player of redox regulation in cardiovascular diseases","volume":"65","year":"2016","journal-title":"Physiol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1097\/HJH.0000000000000627","article-title":"Aerobic exercise training increases nitrergic innervation function and decreases sympathetic innervation function in mesenteric artery from rats fed a high-fat diet","volume":"33","author":"Sastre","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R840","DOI":"10.1152\/ajpregu.00308.2014","article-title":"Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats","volume":"308","author":"Javkhedkar","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13293-019-0236-8","article-title":"The role of the gut microbiome in sex differences in arterial pressure","volume":"10","author":"Beale","year":"2019","journal-title":"Biol. Sex Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3945\/ajcn.110.010132","article-title":"Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans","volume":"94","author":"Jumpertz","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","first-page":"240","article-title":"Microbiota intestinal en la salud y la enfermedad","volume":"78","year":"2013","journal-title":"Rev. Gastroenterol. Mex."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1002\/mnfr.201500290","article-title":"Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats","volume":"59","author":"Toral","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ijfoodmicro.2004.05.012","article-title":"Monostrain, multistrain and multispecies probiotics\u2014A comparison of functionality and efficacy","volume":"96","author":"Timmerman","year":"2004","journal-title":"Int J. Food Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrgastro.2017.75","article-title":"Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics","volume":"14","author":"Gibson","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114599000471","article-title":"Scientific concepts of functional foods in Europe: Consensus Document","volume":"81","author":"Diplock","year":"1999","journal-title":"Br. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1021\/jf0500684","article-title":"In vitro investigation into the potential prebiotic activity of honey oligosaccharides","volume":"53","author":"Sanz","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0006-8993(71)90369-6","article-title":"Ultrastructure of the autonomic innervation apparatus in the main pial arteries of rats and cats","volume":"27","author":"Nielsen","year":"1971","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/SHK.0b013e31826240ba","article-title":"Effects of lipopolysaccharide on the neuronal control of mesenteric vascular tone in rats: Mechanisms involved","volume":"38","author":"Sastre","year":"2012","journal-title":"Shock"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sastre, E., Caracuel, L., Blanco-Rivero, J., Callejo, M., Xavier, F.E., and Balfag\u00f3n, G. (2016). Biphasic Effect of Diabetes on Neuronal Nitric Oxide Release in Rat Mesenteric Arteries. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156793"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/01.HYP.0000171479.36880.17","article-title":"Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats","volume":"46","author":"Cachofeiro","year":"2005","journal-title":"Hypertension"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"575294","DOI":"10.3389\/fphar.2020.575294","article-title":"The Combination of Scutellaria baicalensis Georgi and Sophora japonica, L. ameliorate Renal Function by Regulating Gut Microbiota in Spontaneously Hypertensive Rats","volume":"11","author":"Guan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/10641963.2021.1991942","article-title":"Ethanolic extract of Cissus quadrangularis improves vasoreactivity by modulation of eNOS expression and oxidative stress in spontaneously hypertensive rats","volume":"44","author":"Syed","year":"2022","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1161\/HYPERTENSIONAHA.114.03469","article-title":"Effect of probiotics on blood pressure: A systematic review and meta-analysis of randomized, controlled trials","volume":"64","author":"Khalesi","year":"2014","journal-title":"Hypertension"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hadi, A., Pourmasoumi, M., Kazemi, M., Najafgholizadeh, A., and Marx, W. (2021). Efficacy of synbiotic interventions on blood pressure: A systematic review and meta-analysis of clinical trials. Crit. Rev. Food Sci. Nutr., 1\u201311.","DOI":"10.1080\/10408398.2021.1888278"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106061","DOI":"10.1016\/j.phrs.2022.106061","article-title":"Impact of synbiotic supplementation on cardiometabolic and anthropometric indices in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials","volume":"176","author":"Arabi","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1042\/CS20120651","article-title":"New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension","volume":"126","author":"Hernanz","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Amor, M., Garc\u00eda-Redondo, A.B., Jorge, I., Zalba, G., Becares, M., Ruiz-Rodr\u00edguez, M.J., Rodr\u00edguez, C., Bermeo, H., Rodrigues-D\u00edez, R., and Rios, F.J. (2021). Interferon stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress. Cardiovasc. Res., cvab321.","DOI":"10.1093\/cvr\/cvab321"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1161\/HYPERTENSIONAHA.121.17955","article-title":"Immune System and Microvascular Remodeling in Humans","volume":"79","author":"Rizzoni","year":"2022","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1042\/CS20110523","article-title":"Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats","volume":"122","author":"Bomfim","year":"2012","journal-title":"Clin. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2000005","DOI":"10.1002\/mnfr.202000005","article-title":"The Beneficial Effects of Lippia Citriodora Extract on Diet-Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition","volume":"64","author":"Vezza","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_43","doi-asserted-by":"crossref","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":"ref_44","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41371-020-0388-3","article-title":"Diet-related gut microbial metabolites and sensing in hypertension","volume":"35","author":"Muralitharan","year":"2021","journal-title":"J. Hum. Hypertens."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev-immunol-051116-052235","article-title":"Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related Immune Regulation","volume":"35","author":"Tan","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1084\/jem.2017177301022018c","article-title":"Correction: The immunology of hypertension","volume":"215","author":"Norlander","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41577-019-0160-5","article-title":"Immune mechanisms of hypertension","volume":"19","author":"Drummond","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1073\/pnas.1215927110","article-title":"Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation","volume":"110","author":"Pluznick","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/MNH.0000000000000246","article-title":"The role of short-chain fatty acid on blood pressure regulation","volume":"25","author":"Miyamoto","year":"2016","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1093\/cvr\/cvaa083","article-title":"Blood pressure changes correlate with short-chain fatty acid production potential shifts under a synbiotic intervention","volume":"116","author":"Bartolomaeus","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1900616","DOI":"10.1002\/mnfr.201900616","article-title":"Probiotics Prevent Dysbiosis and the Rise in Blood Pressure in Genetic Hypertension: Role of Short-Chain Fatty Acids","volume":"64","author":"Toral","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1093\/jn\/129.12.2231","article-title":"Prolonged intake of fructo-oligosaccharides induces a short-term elevation of lactic acid-producing bacteria and a persistent increase in cecal butyrate in rats","volume":"129","author":"Michel","year":"1999","journal-title":"J. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1017\/S0007114513000809","article-title":"Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum","volume":"110","author":"Jakobsdottir","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1152\/physiolgenomics.00081.2016","article-title":"Alterations in the gut microbiota can elicit hypertension in rats","volume":"49","author":"Adnan","year":"2017","journal-title":"Physiol. Genom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.aquaculture.2016.11.034","article-title":"The effects of dietary fructooligosaccharide on growth, intestinal short chain fatty acids level and hepatopancreatic condition of the giant freshwater prawn (macrobrachium rosenbergii) post-larvae","volume":"469","author":"Chen","year":"2017","journal-title":"Aquaculture"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1042\/CS20130339","article-title":"The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice","volume":"127","author":"Toral","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/CIRCRESAHA.118.313565","article-title":"Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men with Stable Coronary Artery Disease","volume":"123","author":"Malik","year":"2018","journal-title":"Circ. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/ajh\/hpaa103","article-title":"Microbiota and Hypertension: Role of the Sympathetic Nervous System and the Immune System","volume":"33","author":"Toral","year":"2020","journal-title":"Am. J. Hypertens."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1161\/CIRCRESAHA.116.309006","article-title":"Hypertension-Linked Pathophysiological Alterations in the Gut","volume":"120","author":"Santisteban","year":"2017","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1161\/CIRCRESAHA.119.313965","article-title":"Impaired Autonomic Nervous System-Microbiome Circuit in Hypertension","volume":"125","author":"Zubcevic","year":"2019","journal-title":"Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1111\/bph.14965","article-title":"Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects","volume":"177","author":"Toral","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fphys.2019.00231","article-title":"Critical Role of the Interaction Gut Microbiota\u2013Sympathetic Nervous System in the Regulation of Blood Pressure","volume":"10","author":"Toral","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yi, R., Tan, F., Liao, W., Wang, Q., Mu, J., Zhou, X., Yang, Z., and Zhao, X. (2019). Isolation and Identification of Lactobacillus plantarum HFY05 from Natural Fermented Yak Yogurt and Its Effect on Alcoholic Liver Injury in Mice. Microorganisms, 7.","DOI":"10.3390\/microorganisms7110530"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"H839","DOI":"10.1152\/ajpheart.00278.2021","article-title":"Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function","volume":"321","author":"Aboulgheit","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8013681","DOI":"10.1155\/2021\/8013681","article-title":"Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1172\/JCI123825","article-title":"Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure","volume":"129","author":"Iring","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1080\/10641963.2019.1665676","article-title":"Dietary capsaicin-mediated attenuation of hypertension in a rat model of renovascular hypertension","volume":"42","author":"Segawa","year":"2020","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"114728","DOI":"10.1016\/j.jep.2021.114728","article-title":"Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-\u03b6 to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression","volume":"284","author":"Lin","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3945\/jn.109.114553","article-title":"A Bifidobacterium probiotic strain and its soluble factors alleviate chloride secretion by human intestinal epithelial cells","volume":"140","author":"Heuvelin","year":"2010","journal-title":"J. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.3748\/wjg.v18.i30.3977","article-title":"Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice","volume":"18","author":"Zhou","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1017\/S0007114515002469","article-title":"Supplementary heat-killed Lactobacillus reuteri GMNL-263 ameliorates hyperlipidaemic and cardiac apoptosis in high-fat diet-fed hamsters to maintain cardiovascular function","volume":"114","author":"Ting","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3920\/BM2017.0107","article-title":"Lactobacillus fermentum L930BB and Bifidobacterium animalis subsp. animalis IM386 initiate signalling pathways involved in intestinal epithelial barrier protection","volume":"9","author":"Juvan","year":"2018","journal-title":"Benef. Microbes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molimm.2018.09.001","article-title":"Probiotics SOD inhibited food allergy via downregulation of STAT6-TIM4 signaling on DCs","volume":"103","author":"Yang","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13287-019-1324-8","article-title":"Lactobacillus reuteri extracts promoted wound healing via PI3K\/AKT\/\u03b2-catenin\/TGF\u03b21 pathway","volume":"10","author":"Han","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s12602-019-09576-z","article-title":"Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H2O2-Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes","volume":"12","author":"Kumar","year":"2020","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.vph.2018.05.001","article-title":"Thyroid hormones affect nitrergic innervation function in rat mesenteric artery: Role of the PI3K\/AKT pathway","volume":"108","year":"2018","journal-title":"Vascul. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0828-282X(06)70314-2","article-title":"Reactive oxygen species and vascular remodelling in hypertension: Still alive","volume":"22","author":"Xu","year":"2006","journal-title":"Can. J. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1161\/HYPERTENSIONAHA.107.089284","article-title":"NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat","volume":"50","author":"Wei","year":"2007","journal-title":"Hypertension"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S170","DOI":"10.2337\/dc08-s247","article-title":"NADPH oxidases, reactive oxygen species, and hypertension: Clinical implications and therapeutic possibilities","volume":"31","author":"Paravicini","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"406960","DOI":"10.1155\/2014\/406960","article-title":"Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension","volume":"2014","author":"Dinh","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_81","first-page":"164","article-title":"Aerobic exercise training avoids endothelial and neuronal dysfunction produced by a high fat diet in rat mesenteric artery","volume":"25","author":"Sastre","year":"2014","journal-title":"Trauma Fund MAPFRE"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e1800298","DOI":"10.1002\/mnfr.201800298","article-title":"The Probiotic Lactobacillus fermentum Prevents Dysbiosis and Vascular Oxidative Stress in Rats with Hypertension Induced by Chronic Nitric Oxide Blockade","volume":"62","author":"Toral","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"21397","DOI":"10.1038\/s41598-021-00601-2","article-title":"Synbiotic (Lactiplantibacillus pentosus GSSK2 and isomalto-oligosaccharides) supplementation modulates pathophysiology and gut dysbiosis in experimental metabolic syndrome","volume":"11","author":"Khanna","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T.U., Kim, H.W., and Kim, W. (2021). Effects of Probiotics, Prebiotics, and Synbiotics on Uremic Toxins, Inflammation, and Oxidative Stress in Hemodialysis Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194456"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1111\/1750-3841.15690","article-title":"Evaluation of the efficacy of probiotic VSL#3 and synbiotic VSL#3 and yacon-based product in reducing oxidative stress and intestinal permeability in mice induced to colorectal carcinogenesis","volume":"86","author":"Cruz","year":"2021","journal-title":"J. Food Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s12011-019-01952-8","article-title":"Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: The Role of Oxidative Stress and Cyclooxygenase-2","volume":"196","author":"Fardin","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1111\/1440-1681.13577","article-title":"Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats","volume":"48","author":"Hosseinifard","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1178638820925092","DOI":"10.1177\/1178638820925092","article-title":"Antioxidative and Metabolic Effects of Lactobacillus plantarum, Inulin, and Their Synbiotic on the Hypothalamus and Serum of Healthy Rats","volume":"13","author":"Hosseinifard","year":"2020","journal-title":"Nutr. Metab. Insights"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/13880209.2021.1916542","article-title":"Tocopheryl quinone improves non-alcoholic steatohepatitis (NASH) associated dysmetabolism of glucose and lipids by upregulating the expression of glucagon-like peptide 1 (GLP-1) via restoring the balance of intestinal flora in rats","volume":"59","author":"Sun","year":"2021","journal-title":"Pharm. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Tsao, S.P., Nurrahma, B.A., Kumar, R., Wu, C.H., Yeh, T.H., Chiu, C.C., Lee, Y.P., Liao, Y.C., Huang, C.H., and Yeh, Y.T. (2021). Probiotic Enhancement of Antioxidant Capacity and Alterations of Gut Microbiota Composition in 6-Hydroxydopamin-Induced Parkinson\u2019s Disease Rats. Antioxidants, 10.","DOI":"10.3390\/antiox10111823"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9632","DOI":"10.1039\/D1FO00277E","article-title":"Exopolysaccharides produced by Lactobacillus rhamnosus GG alleviate hydrogen peroxide-induced intestinal oxidative damage and apoptosis through the Keap1\/Nrf2 and Bax\/Bcl-2 pathways in vitro","volume":"12","author":"Li","year":"2021","journal-title":"Food Funct."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.2147\/DDDT.S292243","article-title":"Lactobacillus plantarum ZS62 Alleviates Alcohol-Induced Gastric Injury in Mice via an Anti-Oxidative Mechanism","volume":"15","author":"Wu","year":"2021","journal-title":"Drug Des. Dev. Ther."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/4\/680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:47:01Z","timestamp":1760136421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/4\/680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":92,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["antiox11040680"],"URL":"https:\/\/doi.org\/10.3390\/antiox11040680","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]}}}