{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T17:40:13Z","timestamp":1769881213354,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u2018DIREZIONE GENERALE RICERCA, INNOVAZIONE, UNIVERSITA\u2019 EXPORT E INTERNAZIONALIZZAZIONE act n\u00b0511 of the Lombardy Region, Italy","award":["DECRETO N. 9463 03\/08\/2020"],"award-info":[{"award-number":["DECRETO N. 9463 03\/08\/2020"]}]},{"name":"EPO.MiO\u2014Gli estratti vegetali per la salute del cavo orale con un impatto fisiologico sistemico","award":["DECRETO N. 9463 03\/08\/2020"],"award-info":[{"award-number":["DECRETO N. 9463 03\/08\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5\u201330 ng\/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p &lt; 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract.<\/jats:p>","DOI":"10.3390\/molecules29030586","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T06:54:12Z","timestamp":1706165652000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vitro Assessment of Cortisol Release Inhibition, Bioaccessibility and Bioavailability of a Chemically Characterized Scutellaria lateriflora L. Hydroethanolic Extract"],"prefix":"10.3390","volume":"29","author":[{"given":"Daniele Giuseppe","family":"Buccato","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-676X","authenticated-orcid":false,"given":"Hammad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza Francesca","family":"De Lellis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Piccinocchi","sequence":"additional","affiliation":[{"name":"Level 1 Medical Director Anaesthesia and Resuscitation A. U. O. Luigi Vanvitelli, Via Santa Maria di Costantinopoli, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2877-9445","authenticated-orcid":false,"given":"Alessandra","family":"Baldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-0066","authenticated-orcid":false,"given":"Carla Renata","family":"Arciola","sequence":"additional","affiliation":[{"name":"Laboratory of Immunorheumatology and Regenerative Medicine, Laboratory of Pathology of Implant Infections, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-9976","authenticated-orcid":false,"given":"Alessandro","family":"Di Minno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"},{"name":"CEINGE-BiotecnologieAvanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-7713","authenticated-orcid":false,"given":"Maria","family":"Daglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy"},{"name":"International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"ref_1","first-page":"22","article-title":"Current status of research on medicinal plant Scutellaria lateriflora: A review","volume":"11","author":"Sherman","year":"2022","journal-title":"J. Med. Act. Plants"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.hermed.2012.06.004","article-title":"Skullcap Scutellaria lateriflora L.: An American nervine","volume":"2","author":"Upton","year":"2012","journal-title":"J. Herb. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ullah, H., Minno, A.D., Filippis, A.D., Sommella, E., Buccato, D.G., Lellis, L.F.D., El-Seedi, H.R., Khalifa, S.A., Piccinocchi, R., and Galdiero, M. (2023). In vitro antimicrobial and antibiofilm properties and bioaccessibility after oral digestion of chemically characterized extracts obtained from Cistus \u00d7 incanus L., Scutellaria lateriflora L., and their combination. Foods, 12.","DOI":"10.3390\/foods12091826"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/BF00840509","article-title":"Correction by natural adaptogens of hormonal-metabolic status disorders in rats during the development of adaptation syndrome using functional tests with dexamethasone and ACTH","volume":"112","author":"Udintsev","year":"1991","journal-title":"Biull. Eksp. Biol. Med."},{"key":"ref_5","first-page":"34","article-title":"Anti-stress Effect of Scutellatia baicalensis in SD Rats and ICR Mice","volume":"12","author":"Ryu","year":"2004","journal-title":"Biomol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/ptr.2233","article-title":"Schizandra chinensis and Scutellaria baicalensis counter stress behaviors in mice","volume":"21","author":"Lee","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.neuroimage.2009.05.074","article-title":"The brain and the stress axis: The neural correlates of cortisol regulation in response to stress","volume":"47","author":"Dedovic","year":"2009","journal-title":"Neuroimage"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8313","DOI":"10.1038\/s41598-017-08918-7","article-title":"Amygdala-centred functional connectivity affects daily cortisol concentrations: A putative link with anxiety","volume":"7","author":"Hakamata","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5483\/BMBRep.2015.48.4.275","article-title":"Technical and clinical aspects of cortisol as a biochemical marker of chronic stress","volume":"48","author":"Lee","year":"2015","journal-title":"BMB Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.biopsycho.2010.04.006","article-title":"Morningness\u2013eveningness, habitual sleep-wake variables and cortisol level","volume":"85","author":"Randler","year":"2010","journal-title":"Biol. Psychol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.slsci.2015.09.002","article-title":"Interactions between sleep, stress, and metabolism: From physiological to pathological conditions","volume":"8","author":"Hirotsu","year":"2015","journal-title":"Sleep Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0022-3999(97)00302-4","article-title":"Chronic insomnia and activity of the stress system: A preliminary study","volume":"45","author":"Vgontzas","year":"1998","journal-title":"J. Psychosom. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1210\/jcem.86.8.7778","article-title":"Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: Clinical implications","volume":"86","author":"Vgontzas","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","first-page":"S57","article-title":"Neuroendocrine dysregulation in primary insomnia","volume":"157","author":"Rodenbeck","year":"2001","journal-title":"Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dziurkowska, E., and Wesolowski, M. (2021). Cortisol as a biomarker of mental disorder severity. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215204"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/BF03345601","article-title":"Skeletal involvement in adult patients with endogenous hypercortisolism","volume":"31","author":"Chiodini","year":"2008","journal-title":"J. Endocrinol. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2174\/138955707780619653","article-title":"Pharmacological therapy of Cushing\u2019s syndrome: Drugs and indications","volume":"7","author":"Diez","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104420","DOI":"10.1016\/j.psyneuen.2019.104420","article-title":"Baseline cortisol and the efficacy of antiglucocorticoid treatment in mood disorders: A meta-analysis","volume":"110","author":"Lombardo","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garzarella, E.U., Navajas-Porras, B., P\u00e9rez-Burillo, S., Ullah, H., Esposito, C., Santarcangelo, C., Hinojosa-Nogueira, D., Pastoriza, S., Zaccaria, V., and Xiao, J. (2022). Evaluating the effects of a standardized polyphenol mixture extracted from poplar-type propolis on healthy and diseased human gut microbiota. Biom. Pharmacother., 148.","DOI":"10.1016\/j.biopha.2022.112759"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wojtunik-Kulesza, K., Oniszczuk, A., Oniszczuk, T., Combrzy\u0144ski, M., Nowakowska, D., and Matwijczuk, A. (2020). Influence of in vitro digestion on composition, bioaccessibility and antioxidant activity of food polyphenols\u2014A non-systematic review. Nutrients, 12.","DOI":"10.3390\/nu12051401"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.foodchem.2011.10.030","article-title":"Bioaccessible and dialysable polyphenols in selected apple varieties following in vitro digestion vs. their native patterns","volume":"131","author":"Bouayed","year":"2012","journal-title":"Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110767","DOI":"10.1016\/j.foodres.2021.110767","article-title":"Effect of in vitro digestion on the bioaccessibility and bioactivity of phenolic compounds in fractions of Eugenia pyriformis fruit","volume":"150","author":"Delafiori","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1021\/jf0342627","article-title":"Stability and bioaccessibility of isoflavones from soy bread during in vitro digestion","volume":"51","author":"Walsh","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.fitote.2018.06.018","article-title":"A strategy to improve the oral availability of baicalein: The baicalein-theophylline cocrystal","volume":"129","author":"Li","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1021\/acs.cgd.6b01863","article-title":"Cocrystals of baicalein with higher solubility and enhanced bioavailability","volume":"17","author":"Zhu","year":"2017","journal-title":"Cryst. Growth Des."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.foodchem.2006.06.025","article-title":"Stability of polyphenols in chokeberry (Aronia melanocarpa) subjected to in vitro gastric and pancreatic digestion","volume":"102","year":"2007","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.canlet.2017.10.041","article-title":"Apigenin: A dietary flavonoid with diverse anticancer properties","volume":"413","author":"Gajski","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1080\/10717544.2017.1311968","article-title":"A novel matrix dispersion based on phospholipid complex for improving oral bioavailability of baicalein: Preparation, in vitro and in vivo evaluations","volume":"24","author":"Zhou","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.2174\/187152012803833107","article-title":"Bioavailability and pharmacokinetics of genistein: Mechanistic studies on its ADME","volume":"12","author":"Yang","year":"2012","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2986796","DOI":"10.1155\/2016\/2986796","article-title":"Mechanisms of neuroprotection by quercetin: Counteracting oxidative stress and more","volume":"2016","author":"Costa","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2174\/1389201015666141202110216","article-title":"Naringenin and atherosclerosis: A review of literature","volume":"16","author":"Orhan","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6169","DOI":"10.1080\/10408398.2021.1898333","article-title":"The fate of flavonoids after oral administration: A comprehensive overview of its bioavailability","volume":"62","author":"Naeem","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1124\/dmd.111.040550","article-title":"Absorption and disposition of scutellarin in rats: A pharmacokinetic explanation for the high exposure of its isomeric metabolite","volume":"39","author":"Gao","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref_34","first-page":"477","article-title":"Study on the role of hepatic first-pass elimination in the low oral bioavailability of scutellarin in rats","volume":"60","author":"Hao","year":"2005","journal-title":"Pharmazie"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1039\/C6FO01475E","article-title":"Gastrointestinal interactions, absorption, splanchnic metabolism and pharmacokinetics of orally ingested phenolic compounds","volume":"8","author":"Chen","year":"2017","journal-title":"Food Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/jn\/136.1.45","article-title":"Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods","volume":"136","author":"Cassidy","year":"2006","journal-title":"J. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jchromb.2015.11.049","article-title":"Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-\u03b2-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat","volume":"1026","author":"Cai","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104480","DOI":"10.1016\/j.fitote.2020.104480","article-title":"Pharmacokinetics, tissue distribution and excretion study of Oroxylin A, Oroxylin A 7-O-glucuronide and Oroxylin A sodium sulfonate in rats after administration of Oroxylin A","volume":"142","author":"Ren","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sajeev, A., Hegde, M., Girisa, S., Devanarayanan, T.N., Alqahtani, M.S., Abbas, M., Sil, S.K., Sethi, G., Chen, J.T., and Kunnumakkara, A.B. (2022). Oroxylin A: A promising flavonoid for prevention and treatment of chronic diseases. Biomolecules, 12.","DOI":"10.3390\/biom12091185"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1002\/ptr.5694","article-title":"Overview of oroxylin A: A promising flavonoid compound","volume":"30","author":"Lu","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"921553","DOI":"10.3389\/fphar.2022.921553","article-title":"Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0306-4530(90)90043-9","article-title":"Reduction in urinary free cortisol during benzodiazepine treatment of panic disorder","volume":"15","author":"Lopez","year":"1990","journal-title":"Psychoneuroendocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1055\/s-2007-979494","article-title":"Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder","volume":"30","author":"Bandelow","year":"1997","journal-title":"Pharmacopsychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0301-0511(02)00128-X","article-title":"An investigation into the relationship between salivary cortisol, stress, anxiety and depression","volume":"62","author":"Vedhara","year":"2003","journal-title":"Biol. Psychol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/PSY.0b013e3181d2f0c8","article-title":"Salivary cortisol levels in persons with and without different anxiety disorders","volume":"72","author":"Vreeburg","year":"2010","journal-title":"Psychosom. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1039\/C3FO60702J","article-title":"A standardised static in vitro digestion method suitable for food\u2013an international consensus","volume":"5","author":"Minekus","year":"2014","journal-title":"Food Funct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"Hubatsch","year":"2007","journal-title":"Nat. Protoc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/3\/586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:49:03Z","timestamp":1760104143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/3\/586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,25]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["molecules29030586"],"URL":"https:\/\/doi.org\/10.3390\/molecules29030586","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,25]]}}}