{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:23:51Z","timestamp":1783113831803,"version":"3.54.6"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1A2C2009095"],"award-info":[{"award-number":["NRF-2021R1A2C2009095"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and Cutibacterium acnes (CA: formerly Propionibacterium acnes) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Rhus verniciflua Stokes and Orostachys japonicus, against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-\u03b1, IL-6, p-STAT-3, and p-NF-\u03baB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5\u03b1-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.<\/jats:p>","DOI":"10.3390\/pharmaceutics15071885","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:33:42Z","timestamp":1688517222000},"page":"1885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy of FRO on Acne Vulgaris Pathogenesis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-3576","authenticated-orcid":false,"given":"Jung-Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-743X","authenticated-orcid":false,"given":"Hengmin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cancer Preventive Material Development, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdamun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Science & Services, Eulji University, Seongnam 13135, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-7842","authenticated-orcid":false,"given":"Hyo-Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"},{"name":"Department of Cancer Preventive Material Development, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdamun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.21037\/tlcr.2019.08.25","article-title":"Targeting PKCiota-PAK1 in EGFR-mutation positive non-small cell lung cancer","volume":"8","author":"Ito","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.foodchem.2009.10.051","article-title":"Rhus verniciflua Stokes flavonoid extracts have anti-oxidant, anti-microbial and \u03b1-glucosidase inhibitory effect","volume":"120","author":"Kim","year":"2010","journal-title":"Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.phytochem.2013.05.005","article-title":"Polyphenols from the bark of Rhus verniciflua and their biological evaluation on antitumor and anti-inflammatory activities","volume":"92","author":"Kim","year":"2013","journal-title":"Phytochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10068-014-0037-0","article-title":"Anti-cancer activity of the ethylacetate fraction from Orostachys japonicus for modulation of the signaling pathway in HepG2 human hepatoma cells","volume":"23","author":"Lee","year":"2014","journal-title":"Food Sci. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1002\/fsn3.1207","article-title":"Orostachys japonicus exerts antipancreatic cancer activity through induction of apoptosis and cell cycle arrest in PANC-1 cells","volume":"7","author":"Kim","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8951510","DOI":"10.1155\/2019\/8951510","article-title":"Anticancer Effect of the Ethyl Acetate Fraction from Orostachys japonicus on MDA-MB-231 Human Breast Cancer Cells through Extensive Induction of Apoptosis, Cell Cycle Arrest, and Antimetastasis","volume":"2019","author":"Kwon","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med. eCAM"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1002\/fsn3.836","article-title":"Orostachys japonicus induce p53-dependent cell cycle arrest through the MAPK signaling pathway in OVCAR-3 human ovarian cancer cells","volume":"6","author":"Lee","year":"2018","journal-title":"Food Sci. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1248\/bpb.35.660","article-title":"Effects of the ethylacetate extract of Orostachys japonicus on induction of apoptosis through the p53-mediated signaling pathway in human gastric cancer cells","volume":"35","author":"Ryu","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112664","DOI":"10.1016\/j.jep.2020.112664","article-title":"Cultivated Orostachys japonicus extract inhibits VEGF-induced angiogenesis via regulation of VEGFR2 signaling pathway in vitro and in vivo","volume":"256","author":"Cho","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lee, S.G., Kim, J.S., Lee, H.S., Lim, Y.M., So, J.H., Hahn, D., Ha, Y.S., and Nam, J.O. (2017). Bioconverted Orostachys japonicas Extracts Suppress Angiogenic Activity of Ms-1 Endothelial Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122615"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18407","DOI":"10.3390\/ijms140918407","article-title":"Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP prostate carcinoma cells by inactivating Akt and modulating tight junctions","volume":"14","author":"Shin","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3892\/mmr.2015.3460","article-title":"Orostachys japonicus inhibits the expression of MMP-2 and MMP-9 mRNA and modulates the expression of iNOS and COX-2 genes in human PMA-differentiated THP-1 cells via inhibition of NF-kappaB and MAPK activation","volume":"12","author":"Kim","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_13","first-page":"111","article-title":"Antimetastatic effect of several crude drugs with antitumor activity on B16-Fo and A549 cells (I)","volume":"17","author":"Kim","year":"1996","journal-title":"J. Korean Med."},{"key":"ref_14","unstructured":"Lall, N. (2017). Medicinal Plants for Holistic Health and Well-Being, Academic Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21104","DOI":"10.1038\/s41598-022-25436-3","article-title":"Skin dysbiosis and Cutibacterium acnes biofilm in inflammatory acne lesions of adolescents","volume":"12","author":"Cavallo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_16","unstructured":"US Department of Health Human Services Food Drug Administration Center for Drug Evaluation Research (2005). Guidance for Industry, Acne Vulgaris: Developing Drugs for Treatment."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s40257-020-00542-y","article-title":"Effects of Diet on Acne and Its Response to Treatment","volume":"22","author":"Baldwin","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.clinbiochem.2011.06.984","article-title":"Role of hormones in acne vulgaris","volume":"44","author":"Arora","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1001\/archderm.138.12.1584","article-title":"Acne vulgaris: A disease of Western civilization","volume":"138","author":"Cordain","year":"2002","journal-title":"Arch. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-2265.1998.00356.x","article-title":"Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome","volume":"48","author":"Klinger","year":"1998","journal-title":"Clin. Endocrinol."},{"key":"ref_21","first-page":"s7","article-title":"Advances in the Understanding of the Pathogenesis of Inflammatory Acne","volume":"15","author":"Kircik","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s40168-018-0558-5","article-title":"Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris","volume":"6","author":"Gallo","year":"2018","journal-title":"Microbiome"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mce.2017.09.009","article-title":"Androgens and androgen receptor action in skin and hair follicles","volume":"465","author":"Ceruti","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s13555-019-00320-7","article-title":"Antimicrobial Susceptibility, Biotypes and Phylotypes of Clinical Cutibacterium (Formerly Propionibacterium) acnes Strains Isolated from Acne Patients: An Observational Study","volume":"9","author":"Zhang","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"262","DOI":"10.2340\/00015555-2847","article-title":"Decrease in Diversity of Propionibacterium acnes Phylotypes in Patients with Severe Acne on the Back","volume":"98","author":"Dagnelie","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s00403-010-1074-z","article-title":"Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes","volume":"302","author":"Lee","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ryu, S., Han, H.M., Song, P.I., Armstrong, C.A., and Park, Y. (2015). Suppression of Propionibacterium acnes Infection and the Associated Inflammatory Response by the Antimicrobial Peptide P5 in Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132619"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"788358","DOI":"10.3389\/fphar.2021.788358","article-title":"The Protective Effects of Cath-MH With Anti-Propionibacterium Acnes and Anti-Inflammation Functions on Acne Vulgaris","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/j.1600-0625.2009.00891.x","article-title":"Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin","volume":"18","author":"Lyte","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jdermsci.2012.10.009","article-title":"Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-kappaB and AP-1 activation in macrophages","volume":"69","author":"Tsai","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Grange, P.A., Chereau, C., Raingeaud, J., Nicco, C., Weill, B., Dupin, N., and Batteux, F. (2009). Production of superoxide anions by keratinocytes initiates P. acnes-induced inflammation of the skin. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000527"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15029","DOI":"10.1038\/nrdp.2015.29","article-title":"Acne vulgaris","volume":"1","author":"Makrantonaki","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Xu, Y., Cha, J.-S., Lee, S.-O., Ryu, S.-I., Lee, Y.-K., Han, H., Kim, J.-E., Lee, M.-H., Lee, E.-O., and Lee, H.-J. (2021). HMT Exerts an Anticancer Effect by Targeting PAK-1. Appl. Sci., 11.","DOI":"10.3390\/app11136034"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7270","DOI":"10.1021\/acs.jafc.5b01954","article-title":"Fermented Rhus verniciflua Stokes extract exerts an Antihepatic Lipogenic effect in oleic-acid-induced HepG2 cells via Upregulation of AMP-activated protein kinase","volume":"63","author":"Lee","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lee, S.-O., Kim, S.-J., Kim, J.-S., Ji, H., Lee, E.-O., and Lee, H.-J. (2018). Comparison of the main components and bioactivity of Rhus verniciflua Stokes extracts by different detoxification processing methods. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2310-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant determinations by the use of a stable free radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1038\/jid.2009.46","article-title":"Involvement of Propionibacterium acnes in the augmentation of lipogenesis in hamster sebaceous glands in vivo and in vitro","volume":"129","author":"Iinuma","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/j.0022-202X.2005.23866.x","article-title":"Augmentation of lipogenesis by 15-deoxy-Delta12,14-prostaglandin J2 in hamster sebaceous glands: Identification of cytochrome P-450-mediated 15-deoxy-Delta12,14-prostaglandin J2 production","volume":"125","author":"Iwata","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1001\/archderm.135.9.1041","article-title":"Androgen metabolism in sebaceous glands from subjects with and without acne","volume":"135","author":"Thiboutot","year":"1999","journal-title":"Arch. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/exd.12291","article-title":"Regional difference in sebum production by androgen susceptibility in human facial skin","volume":"23","author":"Seo","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.14310\/horm.2002.11109","article-title":"The human skin as a hormone target and an endocrine gland","volume":"3","author":"Zouboulis","year":"2004","journal-title":"Hormones"},{"key":"ref_42","first-page":"412","article-title":"Cortexolone 17\u03b1-propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist that Inhibits Production of Lipids and Inflammatory Cytokines from Sebocytes In Vitro","volume":"18","author":"Rosette","year":"2019","journal-title":"J. Drugs Dermatol. JDD"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.tibs.2018.01.005","article-title":"SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond","volume":"43","author":"Ye","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1128\/iai.63.8.3158-3165.1995","article-title":"Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: Implications for chronic inflammatory acne","volume":"63","author":"Vowels","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_45","first-page":"202","article-title":"Oxidants and anti-oxidants status in acne vulgaris patients with varying severity","volume":"44","year":"2014","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jcla.21560","article-title":"Biochemical markers of oxidative and nitrosative stress in acne vulgaris: Correlation with disease activity","volume":"27","author":"Alzolibani","year":"2013","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1017\/S0031182009990473","article-title":"The involvement of TLR2 in cytokine and reactive oxygen species (ROS) production by PBMCs in response to Leishmania major phosphoglycans (PGs)","volume":"136","author":"Kavoosi","year":"2009","journal-title":"Parasitology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ijcard.2004.07.010","article-title":"The relationship between sex hormones and lipid profile in men with coronary artery disease","volume":"101","author":"Wranicz","year":"2005","journal-title":"Int. J. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hur, S., Jang, E., and Lee, J.H. (2021). Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways. Nutrients, 13.","DOI":"10.3390\/nu13020555"},{"key":"ref_50","first-page":"117","article-title":"Phenolic compounds from Orostachys japonicus having anti-HIV-1 protease activity","volume":"6","author":"Park","year":"2000","journal-title":"Nat. Prod. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3746\/jkfn.2015.44.1.097","article-title":"Phenolic contents of different parts of Rhus verniciflua Stokes according to extraction conditions","volume":"44","author":"Park","year":"2015","journal-title":"J. Korean Soc. Food Sci. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110985","DOI":"10.1016\/j.biopha.2020.110985","article-title":"Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases","volume":"133","author":"Bai","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"414","DOI":"10.4062\/biomolther.2015.036","article-title":"Fisetin Suppresses Macrophage-Mediated Inflammatory Responses by Blockade of Src and Syk","volume":"23","author":"Kim","year":"2015","journal-title":"Biomol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0192-0561(99)00024-7","article-title":"Quercetin inhibits LPS-induced nitric oxide and tumor necrosis factor-alpha production in murine macrophages","volume":"21","author":"Ghosh","year":"1999","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s10753-014-0011-2","article-title":"Protective effect of kaempferol on LPS plus ATP-induced inflammatory response in cardiac fibroblasts","volume":"38","author":"Tang","year":"2015","journal-title":"Inflammation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e13534","DOI":"10.1111\/dth.13534","article-title":"A retrospective assessment and comparison of the effectiveness of benzoyl peroxide; the combination of topical niacinamide, gallic acid, and lauric acid; and the combination of benzoyl peroxide and erythromycin in acne vulgaris","volume":"33","author":"Kozan","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yin, J., Hwang, I.H., and Lee, M.W. (2019). Anti-acne vulgaris effect including skin barrier improvement and 5alpha-reductase inhibition by tellimagrandin I from Carpinus tschonoskii. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2734-y"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00210-018-01604-z","article-title":"Topical application of phenolic compounds suppresses Propionibacterium acnes-induced inflammatory responses in mice with ear edema","volume":"392","author":"Zancanaro","year":"2019","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121309","DOI":"10.1016\/j.ijpharm.2021.121309","article-title":"Quercetin loaded cosm-nutraceutical electrospun composite nanofibers for acne alleviation: Preparation, characterization and experimental clinical appraisal","volume":"612","author":"Amer","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hosny, K.M., Al Nahyah, K.S., and Alhakamy, N.A. (2020). Self-Nanoemulsion Loaded with a Combination of Isotretinoin, an Anti-Acne Drug, and Quercetin: Preparation, Optimization, and In Vivo Assessment. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010046"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"119092","DOI":"10.1016\/j.ijpharm.2020.119092","article-title":"Cosm-nutraceutical nanovesicles for acne treatment: Physicochemical characterization and exploratory clinical experimentation","volume":"577","author":"Amer","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Joo, J.H., Han, M.H., Kim, J.I., Kim, J.E., Jung, K.H., Oh, H.S., Chung, Y.S., An, H.J., Lee, J.D., and Moon, G.S. (2022). Antimicrobial Activity of Smilax china L. Root Extracts against the Acne-Causing Bacterium, Cutibacterium acnes, and Its Active Compounds. Molecules, 27.","DOI":"10.3390\/molecules27238331"},{"key":"ref_63","first-page":"473","article-title":"In vitro activity of kaempferol isolated from the Impatiens balsamina alone and in combination with erythromycin or clindamycin against Propionibacterium acnes","volume":"45","author":"Lim","year":"2007","journal-title":"J. Microbiol."},{"key":"ref_64","first-page":"39","article-title":"Cosmetics Material Research of FRO Extract","volume":"4","author":"Park","year":"2021","journal-title":"J. Wellbeing Manag. Appl. Psychol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/7\/1885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:06:03Z","timestamp":1760126763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/7\/1885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,4]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["pharmaceutics15071885"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15071885","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,4]]}}}