{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T22:08:10Z","timestamp":1776377290063,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Human skin is colonized by diverse commensal microbes, making up the skin microbiota (SM), contributing to skin integrity and homeostasis. Many of the beneficial effects aroused by the SM are exerted by microbial metabolites such as short-chain fatty acids (SCFAs), including butyric acid. The SCFAs can be used in cosmetic formulations against skin diseases to protect SM by preserving and\/or restoring their natural balance. Unpleasant sensorial properties and unfavorable physico-chemical properties of butyrate strongly limit its cosmetic use. In contrast, some butyrate derivatives, including phenylalanine butyramide (C13H18N2O2, FBA), a solid form of butyric acid, are odorless while retaining the pharmacokinetic properties and safety profile of butyric acid. This study assessed the FBA\u2019s permeation across the skin and its soothing and anti-reddening potential to estimate its cosmetic application. The dosage method used to estimate FBA\u2019s levels was validated to be sure of analytical results. The FBA diffusion tests were estimated in vitro using a Franz-type vertical diffusion cell. The soothing action was evaluated in vivo by Colorimeter CL400, measuring the erythema index. The results suggest that the FBA represents an innovative way to exploit the benefits of butyric acid in the cosmetic fields since it cannot reach the bloodstream, is odorless, and has a significative soothing action (decrease the erythema index \u221215.7% after 30\u2032, and \u221217.8% after 60\u2032).<\/jats:p>","DOI":"10.3390\/molecules26216611","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:22:24Z","timestamp":1635805344000},"page":"6611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Phenylalanine Butyramide Is a New Cosmetic Ingredient with Soothing and Anti-Reddening Potential"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-6214","authenticated-orcid":false,"given":"Ritamaria","family":"di Lorenzo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonietta","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3529-1819","authenticated-orcid":false,"given":"Lucia","family":"Grumetto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Avagliano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"ImmunoNutritionLab at the CEINGE-Biotecnologie Avanzate s.c.ar.l Research Center, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Fiorenza","family":"de Giovanni di Santa Severina","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"ImmunoNutritionLab at the CEINGE-Biotecnologie Avanzate s.c.ar.l Research Center, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"ImmunoNutritionLab at the CEINGE-Biotecnologie Avanzate s.c.ar.l Research Center, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-1408","authenticated-orcid":false,"given":"Lorella","family":"Paparo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy"},{"name":"ImmunoNutritionLab at the CEINGE-Biotecnologie Avanzate s.c.ar.l Research Center, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Laneri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-1431","authenticated-orcid":false,"given":"Irene","family":"Dini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cardiores.2006.04.008","article-title":"The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases","volume":"71","author":"Acker","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Biernacki, M., Brz\u00f3ska, M.M., Markowska, A., Ga\u0142a\u017cyn-Sidorczuk, M., Cylwik, B., G\u0119gotek, A., and Skrzydlewska, E. (2021). Oxidative Stress and Its Consequences in the Blood of Rats Irradiated with UV: Protective Effect of Cannabidiol. Antioxidants, 10.","DOI":"10.3390\/antiox10060821"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Holban, A.M., and Grumezescu, A.M. (2018). Spices and herbs as therapeutic foods. Food Quality: Balancing Health and Disease, Academic Press, Elsevier.","DOI":"10.1016\/B978-0-12-811442-1.00023-7"},{"key":"ref_4","first-page":"142","article-title":"Protein kinases and transcription factors activation in response to UV-radiation of skin: Implications for carcinogenesis","volume":"13","author":"Ocampo","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_5","first-page":"1","article-title":"Dosage of Bioactive Molecules in the Nutricosmeceutical Helix aspersa Muller Mucus and Formulation of New Cosmetic Cream with Moisturizing Effect","volume":"14","author":"Laneri","year":"2019","journal-title":"Nat. Prod. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dong, K., Goyarts, E., Rella, A., Pelle, E., Wong, Y.H., and Pernodet, N. (2020). Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against UV-Induced DNA Damage. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010326"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dini, I., and Laneri, S. (2021). The New Challenge of Green Cosmetics: Natural Food Ingredients for Cosmetic Formulations. Molecules, 26.","DOI":"10.3390\/molecules26133921"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s40168-021-01062-5","article-title":"Challenges in exploring and manipulating the human skin microbiome","volume":"9","author":"Boxberger","year":"2021","journal-title":"Microbiome."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Pessemier, B., Grine, L., Debaere, M., Maes, A., Paetzold, B., and Callewaert, C. (2021). Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms, 9.","DOI":"10.3390\/microorganisms9020353"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri.2016.48","article-title":"The influence of skin microorganisms on cutaneous immunity","volume":"16","author":"Belkaid","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","first-page":"12","article-title":"The role of cutaneous microbiota harmony in maintaining a functional skin barrier","volume":"16","author":"Baldwin","year":"2017","journal-title":"J. Drugs Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaat8329","DOI":"10.1126\/scitranslmed.aat8329","article-title":"Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis","volume":"11","author":"Williams","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eaah4680","DOI":"10.1126\/scitranslmed.aah4680","article-title":"Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis","volume":"9","author":"Nakatsuji","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_14","first-page":"fiy241","article-title":"Human skin microbiota is a rich source of bacteriocin-producing staphylococci that kill human pathogens","volume":"95","author":"Rea","year":"2019","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/pde.13829","article-title":"Variation of cultured skin microbiota in mothers and their infants during the first year postpartum","volume":"36","author":"Gaitanis","year":"2019","journal-title":"Pediatr. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/ics.12594","article-title":"Revealing the secret life of skin\u2014With the microbiome you never walk alone","volume":"42","author":"Sfriso","year":"2020","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40168-018-0404-9","article-title":"Commensal microbiota modulate gene expression in the skin","volume":"6","author":"Meisel","year":"2018","journal-title":"Microbiome"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dini, I., and Laneri, S. (2021). Spices, Condiments, Extra Virgin Olive Oil and Aromas as Not Only Flavorings, but Precious Allies for Our Wellbeing. Antioxidants, 10.","DOI":"10.3390\/antiox10060868"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Keshari, S., Balasubramaniam, A., Myagmardoloonjin, B., Herr, D.R., Negari, I.P., and Huang, C.-M. (2019). Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184477"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111385","DOI":"10.1016\/j.biopha.2021.111385","article-title":"In vivo bioavailability and in vitro toxicological evaluation of the new butyric acid releaser N-(1-carbamoyl-2-phenyl-ethyl) butyramide","volume":"137","author":"Russo","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","unstructured":"AOAC (2012). Appendix F: Guidelines for Standard Method Performance Requirements (SMPR), AOAC Official Methods of Analysis."},{"key":"ref_22","unstructured":"(2021, August 23). Consolidated Text: Regulation (EC) No 1223\/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products (Recast) (Text with EEA Relevance). Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX%3A02009R1223-20210823."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ng, K.W., and Lau, W.M. (2015). Skin Deep: The Basics of Human Skin Structure and Drug Penetration. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement, Springer.","DOI":"10.1007\/978-3-662-45013-0_1"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Soba\u0144ska, A.W., Robertson, J., and Brzezi\u0144ska, E. (2021). Application of RP-18 TLC Retention Data to the Prediction of the Transdermal Absorption of Drugs. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020147"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Todo, H. (2017). Transdermal Permeation of Drugs in Various Animal Species. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9030033"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Neupane, R., Boddu, S.H.S., Renukuntla, J., Babu, R.J., and Tiwari, A.K. (2020). Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020152"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0168-3659(91)90111-P","article-title":"Epidermal barrier function: Intercellular lamellar lipid structures, origin, composition, and metabolism","volume":"15","author":"Elias","year":"1991","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"xtab003","DOI":"10.1093\/femsmc\/xtab003","article-title":"Isolation and characterization of bacteriophages from the human skin microbiome that infect Staphylococcus epidermidis","volume":"2","author":"Valente","year":"2021","journal-title":"FEMS Microbes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.2217\/fmb-2017-0059","article-title":"Short-chain fatty acids: A link between prebiotics and microbiota in chronic kidney disease","volume":"12","author":"Esgalhado","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jid.2016.11.014","article-title":"The Short-Chain Fatty Acid Sodium Butyrate Functions as a Regulator of the Skin Immune System","volume":"137","author":"Schwarz","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sujka, W., Draczynski, Z., Kolesinska, B., Latanska, I., Jastrzebski, Z., Rybak, Z., and Zywicka, B. (2019). Influence of porous dressings based on butyric-acetic chitin co-polymer on biological processes in vitro and in vivo. Materials, 12.","DOI":"10.3390\/ma12060970"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00441-005-0140-x","article-title":"Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine","volume":"324","author":"Karaki","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Traisaeng, S., Herr, D.R., Kao, H.J., Chuang, T.H., and Huang, C.M. (2019). A derivative of butyric acid, the fermentation metabolite of Staphylococcus epidermidis, inhibits the growth of a Staphylococcus aureus strain isolated from atopic dermatitis patients. Toxins, 11.","DOI":"10.3390\/toxins11060311"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00403-018-1865-1","article-title":"Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate","volume":"310","author":"Krejner","year":"2018","journal-title":"Arch. Dermatol. Res."},{"key":"ref_35","unstructured":"(2021, October 28). European-Chemical-Bureau, Dir 92\/69\/EEC. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX%3A31992L0069."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dini, I., Graziani, G., Fedele, F.L., Sicari, A., Vinale, F., Castaldo, L., and Ritieni, A. (2020). An Environmentally Friendly Practice Used in Olive Cultivation Capable of Increasing Commercial Interest in Waste Products from Oil Processing. Antioxidants, 9.","DOI":"10.3390\/antiox9060466"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2007.08.004","article-title":"In vitro permeation of levothyroxine across the skin","volume":"349","author":"Padula","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1365-2125.2004.02103.x","article-title":"The revision of the Declaration of Helsinki: Past, present and future","volume":"57","author":"Carlson","year":"2004","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Renner, G., Audebert, F., Burfeindt, J., Calvet, B., Caratas-Perifan, M., Leal, M.E., Gorni, R., Long, A., Meredith, E., and O\u2019Sullivan, \u00da. (2017). Cosmetics Europe Guidelines on the Management of Undesirable Effects and Reporting of Serious Undesirable Effects from Cosmetics in the European Union. Cosmetics, 4.","DOI":"10.3390\/cosmetics4010001"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:00Z","timestamp":1760167440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,31]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216611"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216611","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,31]]}}}