{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:00:55Z","timestamp":1775484055959,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age\u2010related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The present study aimed to evaluate the effects of a phytocosmetic formulation containing <jats:italic>Myrothamnus flabellifolia<\/jats:italic> leaf and <jats:italic>Coffea arabica<\/jats:italic> seed plant extracts (MflCas) on the ubiquitin\u2010proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple\u2010blind, and placebo\u2010controlled trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune\u2010enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT\u2010PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Topical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56\u00a0days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56\u00a0days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2\u00a0gene expressions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The phytocosmetic preparation containing <jats:italic>Myrothamnus flabellifolia<\/jats:italic> leaf and <jats:italic>Coffea arabica<\/jats:italic> seed modulated ubiquitin\u2010proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti\u2010aging and lightening agent.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.14888","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T06:04:01Z","timestamp":1645941841000},"page":"4901-4912","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modulation of autophagy by an innovative phytocosmetic preparation (<i>Myrothamnus flabelifolia<\/i> and <i>Coffea arabica<\/i>) in human fibroblasts and its effects in a clinical randomized placebo\u2010controlled trial"],"prefix":"10.1111","volume":"21","author":[{"given":"Rafael C.","family":"Biscaro","sequence":"first","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian","family":"Mussi","sequence":"additional","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Sufi","sequence":"additional","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana","family":"Padovani","sequence":"additional","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio B.","family":"Camargo Junior","sequence":"additional","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wagner V.","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Research and Development Department Chemyunion Qu\u00edmica Ltda  Sorocaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-1073","authenticated-orcid":false,"given":"Luiz C.","family":"Di Stasi","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology Laboratory of Phytomedicines, Pharmacology, and Biotechnology (PhytoPharmaTech) Institute of Biosciences S\u00e3o Paulo State University (Unesp)  Botucatu Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1","article-title":"Relationship between the proteasomal system and autophagy","volume":"4","author":"Lilienbaum A","year":"2013","journal-title":"Int J Biochem Mol Biol"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.11.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070674"},{"key":"e_1_2_9_5_1","first-page":"14","article-title":"Development of autophagy inducers in clinical medicine","volume":"125","author":"Levine B","year":"2015","journal-title":"J Clin Med"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108775"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aac5472"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.28778"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73939"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(99)00101-3"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.05.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0954411918759801"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.12.029"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600599"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.07.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.01.006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.05.009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-39"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14305"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000484629"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.06.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2020.01.006"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071240"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0176-1617(11)81257-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090202"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.05.014"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609532200"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12061842"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2016.11.008"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1473-2165.2009.00425.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1814"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.28929"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14340"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26667"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12876"}],"container-title":["Journal of Cosmetic Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.14888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jocd.14888","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.14888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T13:46:16Z","timestamp":1748353576000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jocd.14888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,12]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/jocd.14888"],"URL":"https:\/\/doi.org\/10.1111\/jocd.14888","archive":["Portico"],"relation":{},"ISSN":["1473-2130","1473-2165"],"issn-type":[{"value":"1473-2130","type":"print"},{"value":"1473-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,12]]},"assertion":[{"value":"2021-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}