{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:19:09Z","timestamp":1783426749551,"version":"3.54.6"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The aim of the present study was to evaluate the bioavailability and associated bioactivity of p-coumaric (p-COA), caffeic (CA), and ferulic (FA) hydroxycinnamic acids (HCAs) isolated from an aqueous extract of plant material. An aqueous extract is more applicable in practice because this form is the most commonly used for oral administration. The p-COA, CA, and FA acids were evaluated for their behavior in the processes of absorption, distribution, metabolism, and excretion (ADME) using modern methods for assessing their functional groups according to Lipinski\u2019s Rule of Five and the Rule of Nines. Given the available data on extensive metabolism of hydroxycinnamic acids during the first pass through the liver, it is necessary to consider an alternative route of administration, namely the sublingual route. Sublingual delivery of exogenous molecules obtained from plant material by extraction may represent a preferable alternative to oral administration, as first-pass hepatic metabolism is bypassed when dosage forms are administered sublingually.<\/jats:p>","DOI":"10.3390\/cimb48070656","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:04:47Z","timestamp":1783418687000},"page":"656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Bioavailability and Related Bioactivity of Hydroxycinnamic Acids"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-7569","authenticated-orcid":false,"given":"Elica","family":"Valkova","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-3382","authenticated-orcid":false,"given":"Vasil","family":"Atanasov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiril","family":"Kirilov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Yakimov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2207-0311","authenticated-orcid":false,"given":"Yordan","family":"Kutsarov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","first-page":"37","article-title":"Chemical constituent and pharmacological importance of Agropyron repens, A review","volume":"1","year":"2015","journal-title":"Res. J. Pharmacol. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jep.2005.06.019","article-title":"Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats","volume":"102","author":"Eddouks","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","unstructured":"European Medicines Agency (2011). Assessment Report on Agropyron repens (L.) P. Beauv., Rhizoma."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/ptr.2650010107","article-title":"Biological screening of Italian medicinal plants for anti-inflammatory activity","volume":"1","author":"Mascolo","year":"1987","journal-title":"Phytother. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11094-009-0231-1","article-title":"Chemical composition of couch grass and studies of its antioxidant activity in allergic contact dermatitis","volume":"43","author":"Petrova","year":"2009","journal-title":"Pharm. Chem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"909","DOI":"10.33224\/rrch\/2019.64.10.10","article-title":"Antioxidant ant antidiabetic properties of polyphenolic-rich extracts of Apium graveolens and Agropyrum repens","volume":"64","author":"Neagu","year":"2019","journal-title":"Rev. Roum. Chim."},{"key":"ref_7","first-page":"777","article-title":"Zur Frage der \u201csedativen\u201d Wirkung von Radix Valerianae","volume":"13","author":"Kiesewetter","year":"1958","journal-title":"Pharmazie"},{"key":"ref_8","first-page":"252","article-title":"Fluid extract of Agropyron repens for the treatment of urinary tract infections or irritable bladder. Results of multicentric post-marketing surveillance","volume":"21","author":"Hautmann","year":"2000","journal-title":"Z. Phytother."},{"key":"ref_9","first-page":"265","article-title":"Izmyenyeniya biologi-chyeskoi, aktivnosti agropiryena priyego prim yenyenii s gumusoymi vye shchyestvami na kul-turuvodorosli Scenedesmus obliquus (Turp.) kr\u00fcger","volume":"6","year":"1964","journal-title":"Biol. Plant"},{"key":"ref_10","first-page":"77","article-title":"Recent results of investigations concerning medicinal plants with \u201caquaretic\u201d, antibacterial and prostatic effects","volume":"10","author":"Schilcher","year":"1989","journal-title":"Z. Phytother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1055\/s-2006-962045","article-title":"Composition of the essential oil of Agropyron repens rhizome","volume":"55","author":"Boesel","year":"1989","journal-title":"Planta Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1055\/s-2006-959672","article-title":"Isolation and structure elucidation of p-hydroxycinnamic acid esters from the rhizome of Agropyron repens, Part I","volume":"59","author":"Koetter","year":"1993","journal-title":"Planta Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1055\/s-2006-959547","article-title":"Isolation and structure elucidation of p-hydroxycinnamic acid esters from the rhizome of Agropyron repens, Part II","volume":"60","author":"Koetter","year":"1994","journal-title":"Planta Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3390\/ijms22010181","article-title":"5-Hydroxytryptophan (5-HTP): Natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology","volume":"22","author":"Maffei","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bortolami, M., Di Matteo, P., Rocco, D., Feroci, M., and Petrucci, R. (2022). Metabolic Profile of Agropyron repens (L.) P. Beauv. Rhizome Herbal Tea by HPLC-PDA-ESI-MS\/MS Analysis. Molecules, 27.","DOI":"10.3390\/molecules27154962"},{"key":"ref_16","first-page":"1","article-title":"Phytochemical study of Elymus repens Gould and Cynodon dactylon (L.) pers","volume":"56","year":"2000","journal-title":"Farm. Glasnik."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1093\/jn\/134.11.3083","article-title":"Ferulic Acid Is Quickly Absorbed from Rat Stomach as the Free Form and Then Conjugated Mainly in Liver","volume":"134","author":"Zhao","year":"2004","journal-title":"J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/bmc.3313","article-title":"Simultaneous Determination of Caffeic Acid and Its Major Pharmacologically Active Metabolites in Rat Plasma by LC-MS\/MS and Its Application in Pharmacokinetic Study","volume":"29","author":"Wang","year":"2015","journal-title":"Biomed. Chromatogr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1007\/s00394-016-1290-1","article-title":"Bioavailability of Chlorogenic Acids in Rats after Acute Ingestion of Mat\u00e9 Tea (Ilex Paraguariensis) or 5-Caffeoylquinic Acid","volume":"56","author":"Sampaio","year":"2017","journal-title":"Eur. J. Chem. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejps.2017.01.011","article-title":"Characterization, Pharmacokinetics and Tissue Distribution of Chlorogenic Acid-Loaded Self-Microemulsifying Drug Delivery System","volume":"100","author":"Chen","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.2147\/IJN.S240449","article-title":"Self-Microemulsifying Drug Delivery System for Improved Oral Delivery and Hypnotic Efficacy of Ferulic Acid","volume":"15","author":"Liu","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.lfs.2003.11.028","article-title":"Orally Administered Rosmarinic Acid Is Present as the Conjugated and\/or Methylated Forms in Plasma, and Is Degraded and Metabolized to Conjugated Forms of Caffeic Acid, Ferulic Acid and m-Coumaric Acid","volume":"75","author":"Baba","year":"2004","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/00498254.2017.1292564","article-title":"Effect of Piperine on the Bioavailability and Pharmacokinetics of Rosmarinic Acid in Rat Plasma Using UPLC-MS\/MS","volume":"48","author":"Yang","year":"2018","journal-title":"Xenobiotica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e4984","DOI":"10.1002\/bmc.4984","article-title":"Rapid Determination of Rosmarinic Acid and Its Two Bioactive Metabolites in the Plasma of Rats by LC-MS\/MS and Application to a Pharmacokinetics Study","volume":"35","author":"Wang","year":"2021","journal-title":"Biomed. Chromatogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1021\/jf3001185","article-title":"Absorption, Disposition, Metabolism, and Excretion of Caffeic Acid in Rats","volume":"60","author":"Omar","year":"2012","journal-title":"J. Caffeic Acid. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.1021\/jf000483q","article-title":"Absorption of Chlorogenic Acid and Caffeic Acid in Rats after Oral Administration","volume":"48","author":"Azuma","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02708","DOI":"10.1016\/j.heliyon.2019.e02708","article-title":"Urinary Excretion Rate and Bioavailability of Chlorogenic Acid, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid in Non-Fasted Rats Maintained under Physiological Conditions","volume":"5","author":"Kishida","year":"2019","journal-title":"Heliyon"},{"key":"ref_28","unstructured":"Boylan, J.C., and Swarbrick, J. (1990). Buccal Absorption of Drugs. Encyclopedia of Pharmaceutical Technology, Marcel Dekker."},{"key":"ref_29","unstructured":"Meyer, J., and Squier, C.A. (1971). Permeability of the Oral Mucosa. Current Concepts of the Histology of Oral Mucosa, Thomas."},{"key":"ref_30","first-page":"31S","article-title":"Buccal Absorption of Basic Drugs and Its Application as an in vivo Model of Passive Drug Transfer Through Lipid Membranes","volume":"19","author":"Beckett","year":"1967","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_31","first-page":"479","article-title":"Influence of pH on Absorption of Thymoxamine Through Buccal Mucosa in Man","volume":"43","author":"Arbab","year":"1971","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S144","DOI":"10.1111\/j.2042-7158.1969.tb08365.x","article-title":"Correlation of Partition Coefficient in n-Heptane-Aqueous Systems with Buccal Absorption Data for A Series of Amines and Acids","volume":"21","author":"Beckett","year":"1969","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.2042-7158.1968.tb09695.x","article-title":"Kinetics of Buccal Absorption of Amphetamines","volume":"20","author":"Triggs","year":"1968","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1177\/00220345680470063001","article-title":"Absorption of Carbon-14 Labeled Lidocaine Through Oral Mucosa","volume":"47","author":"Bergman","year":"1968","journal-title":"J. Dent. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0003-9969(69)90019-3","article-title":"In Vitro and In Situ Transfer of Local Anaesthetics Across Oral Mucosa","volume":"14","author":"Bergman","year":"1969","journal-title":"Arch. Oral Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0378-5173(99)00091-5","article-title":"A Mechanistic Analysis to Characterize Oramucosal Permeation Properties","volume":"184","author":"Chen","year":"1999","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1002\/jps.1136","article-title":"Characterization of Captopril Sublingual Permeation: Determination of Preferred Routes and Mechanisms","volume":"90","author":"Chetty","year":"2001","journal-title":"J. Pharm. Sci."},{"key":"ref_38","first-page":"127","article-title":"Absorption of Sugars from Human Buccal Cavity","volume":"51","author":"Manning","year":"1976","journal-title":"Clin. Sci. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1211\/0022357021778402","article-title":"Transport of D-glucose Across Cultured Stratified Cell Layer of Human Oral Mucosal Cells","volume":"54","author":"Kimura","year":"2002","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1021\/js9703028","article-title":"Perfusion Cells for Studying Regional Variation in Oral Mucosal Permeability in Humans. 2. A Specialized Transport Mechanism in D-Glucose Absorption Exists in Dorsum of Tongue","volume":"87","author":"Kurosaki","year":"1998","journal-title":"J. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1021\/js980298f","article-title":"Carrier-Mediated Transport Systems for Glucose in Mucosal Cells of The Human Oral Cavity","volume":"88","author":"Oyama","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1079\/BJN19790085","article-title":"Absorption of Vitamin-C From The Human Buccal Cavity","volume":"42","author":"Sadooghabasian","year":"1979","journal-title":"Br. J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/0024-3205(80)90638-4","article-title":"Absorption of Nicotinic-Acid and Nicotinamide Across Human Buccal Mucosa In Vivo","volume":"27","author":"Evered","year":"1980","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/0024-3205(83)90810-X","article-title":"Thiamone-Absorption Across Human Buccal Mucosa In Vivo","volume":"32","author":"Evered","year":"1983","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1021\/js970412e","article-title":"Carrier-Mediated Absorption of Salicylic Acid from Hamster Cheek Pouch Mucosa","volume":"88","author":"Utoguchi","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1023\/A:1012046021028","article-title":"Carrier-Mediated Transport of Monocarboxylic Acids in Primary Cultured Epithelial Cells from Rabbit Oral Mucosa","volume":"14","author":"Utoguchi","year":"1997","journal-title":"Pharm. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1902\/jop.2002.73.11.1267","article-title":"An In Vitro Model of Ciprofloxacin and Minocycline Transport by Oral Epithelial Cells","volume":"73","author":"Brayton","year":"2002","journal-title":"J. Periodontol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Di Prima, G., Angellotti, G., Scarpaci, A.G., Murgia, D., D\u2019agostino, F., Campisi, G., and De Caro, V. (2021). Improvement of Resveratrol Permeation through Sublingual Mucosa: Chemical Permeation Enhancers versus Spray Drying Technique to Obtain Fast-Disintegrating Sublingual Mini-Tablets. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091370"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/656\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:48:17Z","timestamp":1783424897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070656"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070656","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}