{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:59:25Z","timestamp":1771473565948,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio","doi-asserted-by":"publisher","award":["CHIRALBIO ACTIVE-PI-3RL-IINFACTS-2019"],"award-info":[{"award-number":["CHIRALBIO ACTIVE-PI-3RL-IINFACTS-2019"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>Human skin aging results from intrinsic and extrinsic factors. Uneven pigmentation is one of the major changes of extrinsic aging. Many compounds have been tested for depigmenting activity but only a few are actually used by the cosmetic industry, which is continually looking for new ingredients. In this study, the trends in the use of skin depigmenting ingredients in a panel of anti-aging formulations commercialized in the Portuguese pharmacy market were analyzed, by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018 (59% and 74%, respectively). The analysis of the top 12 ingredients put forward three novelties for 2018: tranexamic acid, bakuchiol, and 4-butylresorcinol. Regarding their mechanisms of action, tranexamic acid inhibits melanin synthesis through inhibition of the plasminogen\/plasmin system. Bakuchiol depigmenting efficacy was attributed to the ability to block both \u03b1-melanocyte-stimulating hormone and tyrosinase activation, while 4-butylresorcinol exerts its action through the inhibition of both tyrosinase and tyrosinase-related protein-1 (TRP-1). Industry-optimized and efficient synthetic methodologies that embrace green chemistry, reducing the environmental impact, are commonly used. This analysis aims to bring insights to both formulators, involved in the development of depigmenting cosmetic products, and chemists performing the synthesis of new and existing compounds intended for this purpose.<\/jats:p>","DOI":"10.3390\/app12020775","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Skin Depigmenting Agents in Anti-Aging Cosmetics: A Medicinal Perspective on Emerging Ingredients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-6060","authenticated-orcid":false,"given":"Diana I. S. P.","family":"Resende","sequence":"first","affiliation":[{"name":"CIIMAR\u2014Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9064-4859","authenticated-orcid":false,"given":"Marta S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-8397","authenticated-orcid":false,"given":"Jos\u00e9 M. S.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-048X","authenticated-orcid":false,"given":"Isabel F.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MedTech, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4161\/derm.22804","article-title":"Skin anti-aging strategies","volume":"4","author":"Ganceviciene","year":"2012","journal-title":"Dermatoendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jtv.2016.03.002","article-title":"Introduction to skin aging","volume":"26","author":"Tobin","year":"2017","journal-title":"J. Tissue Viability"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1177\/0963689717725755","article-title":"Fighting against Skin Aging:The Way from Bench to Bedside","volume":"27","author":"Zhang","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102273","DOI":"10.1016\/j.algal.2021.102273","article-title":"Trends in the use of marine ingredients in anti-aging cosmetics","volume":"55","author":"Resende","year":"2021","journal-title":"Algal Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ferreira, M.S., Magalh\u00e3es, M.C., Oliveira, R., Sousa-Lobo, J.M., and Almeida, I.F. (2021). Trends in the Use of Botanicals in Anti-Aging Cosmetics. Molecules, 26.","DOI":"10.3390\/molecules26123584"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.clindermatol.2013.05.026","article-title":"Pigmentation disorders: Hyperpigmentation and hypopigmentation","volume":"32","author":"Nicolaidou","year":"2014","journal-title":"Clin. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Opperman, L., De Kock, M., Klaasen, J., and Rahiman, F. (2020). Tyrosinase and Melanogenesis Inhibition by Indigenous African Plants: A Review. Cosmetics, 7.","DOI":"10.3390\/cosmetics7030060"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/jocd.13112","article-title":"Comparing the efficacy of Myjet-assisted tranexamic acid and vitamin C in treating melasma: A split-face controlled trial","volume":"19","author":"Zhao","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1021\/acs.jmedchem.7b00967","article-title":"Inhibitors of Melanogenesis: An Updated Review","volume":"61","author":"Pillaiyar","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_10","first-page":"21","article-title":"Assessment of efficacy, safety, and tolerability of 4-n-butylresorcinol 0.3% cream: An Indian multicentric study on melasma","volume":"9","author":"Mohan","year":"2016","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Couteau, C., and Coiffard, L. (2016). Overview of Skin Whitening Agents: Drugs and Cosmetic Products. Cosmetics, 3.","DOI":"10.3390\/cosmetics3030027"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/bjd.16918","article-title":"Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing","volume":"180","author":"Dhaliwal","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.jid.2018.01.019","article-title":"Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase","volume":"138","author":"Mann","year":"2018","journal-title":"J. Invest. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8101540","DOI":"10.1155\/2018\/8101540","article-title":"Towards Boosting Power by Encapsulating Tranexamic Acid into Emulsified Particles","volume":"2018","author":"Huang","year":"2018","journal-title":"J. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jdermsci.2017.05.019","article-title":"Tranexamic acid inhibits melanogenesis by activating the autophagy system in cultured melanoma cells","volume":"88","author":"Cho","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/jocd.12979","article-title":"Whitening effects of cosmetic formulation in the vascular component of skin pigmentation","volume":"19","author":"Pereira","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Anwar, A.I., Wahab, S., Widita, W., Nurdin, A.R., Budhiani, S., and Seweng, A. (2019). Randomized control trial outcomes of tranexamic acid combination serum as a depigmenting agent for the use in healthy individuals. Dermatol. Ther., 32.","DOI":"10.1111\/dth.13146"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s40257-017-0263-3","article-title":"Tranexamic Acid in the Treatment of Melasma: A Review of the Literature","volume":"18","author":"Perper","year":"2017","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.jpba.2008.09.019","article-title":"Determination of tranexamic acid in cosmetic products by high-performance liquid chromatography coupled with barrel plating nickel electrode","volume":"48","author":"Shih","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_20","first-page":"753","article-title":"Topical tranexamic acid as a promising treatment for melasma","volume":"19","author":"Ebrahimi","year":"2014","journal-title":"J. Res. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3109\/09546634.2015.1115812","article-title":"Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study","volume":"27","author":"Chung","year":"2016","journal-title":"J. Dermatol. Treat."},{"key":"ref_22","first-page":"454","article-title":"Effect of a Tranexamic Acid, Kojic Acid, and Niacinamide Containing Serum on Facial Dyschromia: A Clinical Evaluation","volume":"18","author":"Desai","year":"2019","journal-title":"J. Drugs Dermatol."},{"key":"ref_23","unstructured":"Jiang, Z.L. (2019). Preparation Method of 4-Chloromethyl Benzoic Acid t-Butyl Ester. (1907948A), CN Patent."},{"key":"ref_24","unstructured":"Tao, X., Wang, Z., Wu, J.G., and Dong, D.P. (2014). Method for Preparing Tranexamic Acid from Para-Aminomethylbenzoic Acid by Catalytic Hydrogenation. (102276490A), CN Patent."},{"key":"ref_25","unstructured":"Chang, J. (2014). Novel Technology for Synthesis of Aminomethylbenzoic Acid. (102718673A), CN Patent."},{"key":"ref_26","first-page":"160","article-title":"Observation of Curative Effect of Lipoic Acid in the Treatment of Diabetic Peripheral Neuropathy","volume":"6","author":"Sun","year":"2011","journal-title":"China Prac. Med."},{"key":"ref_27","unstructured":"Jiang, Z.X., Song, Z.F., and Diao, W.R. (2012). Application of Urotropine as Catalyst in Aminomethylbenzoic Acid Synthesis. (102816077A), CN Patent."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1021\/op500395b","article-title":"An Improved and Practical Synthesis of Tranexamic Acid","volume":"19","author":"Li","year":"2015","journal-title":"Org. Process Res. Dev."},{"key":"ref_29","first-page":"269","article-title":"A new synthetic process for tranexamic acid from ethyl 4-oxo-cyclohexane carboxylate","volume":"8","author":"Dodda","year":"2016","journal-title":"Pharma Chem."},{"key":"ref_30","unstructured":"Kalpattu Kuppuswamy, B., Kuppuswamy, V., Mariadas, A.S., and Ganapathi, V. (2021). Greener Process for the Preparation Tranexamic Acid Including a One-Pot Process. (2021111475A1), WO Patent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.6023\/cjoc201408015","article-title":"Chemistry and Biology of Bakuchiol","volume":"34","author":"Huang","year":"2014","journal-title":"Chin. J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1111\/jocd.13708","article-title":"Cosmetic commentary: Is bakuchiol the new \u201cskincare hero\u201d?","volume":"19","author":"Spierings","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/ics.12117","article-title":"Bakuchiol: A retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects","volume":"36","author":"Chaudhuri","year":"2014","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.1080\/14786419.2020.1837813","article-title":"Characteristics of bakuchiol-the compound with high biological activity and the main source of its acquisition\u2014Cullen corylifolium (L.) Medik","volume":"35","author":"Jafernik","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.36849\/JDD.2020.5522","article-title":"Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin","volume":"19","author":"Draelos","year":"2020","journal-title":"J. Drugs Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2147\/CCID.S235880","article-title":"Efficacy of a dermocosmetic serum combining bakuchiol and vanilla tahitensis extract to prevent skin photoaging in vitro and to improve clinical outcomes for naturally aged skin","volume":"13","author":"Bacqueville","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_37","unstructured":"Duplan, H., Bacqueville, D., and Poigny, S. (2019). Tahiti Vanilla Extract and 4-[(1E,3S)-3-ethenyl-3,7-dimethylocta-1,6-dienyl]phenol for Controlling Skin Aging. (2019224303A1), WO Patent."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/jocd.12896","article-title":"Clinical evidence of the efficacy and safety of a new 3-in-1 anti-aging topical night serum-in-oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days","volume":"18","author":"Goldberg","year":"2019","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1021\/acs.orglett.6b02540","article-title":"Enantioselective Synthesis of Quaternary Stereocenters via Chromium Catalysis","volume":"18","author":"Xiong","year":"2016","journal-title":"Org. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3987\/COM-15-S(T)11","article-title":"Synthesis of (S)- and (R)-sporochnol by using the allylic substitution of the secondary allylic picolinate","volume":"93","author":"Kobayashi","year":"2016","journal-title":"Heterocycles"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0923-1811(95)93865-X","article-title":"The inhibitory effects of 4-N-butyl-resorcinol on melanogenesis","volume":"10","author":"Okubo","year":"1995","journal-title":"J. Dermatol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5021\/ad.2010.22.1.21","article-title":"The Efficacy and Safety of 4-n-butylresorcinol 0.1% Cream for the Treatment of Melasma: A Randomized Controlled Split-face Trial","volume":"22","author":"Huh","year":"2010","journal-title":"Ann. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jdermsci.2015.07.007","article-title":"A convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from leukoderma-inducing phenols","volume":"80","author":"Ito","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_44","unstructured":"Bian, F., Si, C., Yu, G., Duan, T., and Li, L. (2021). Composition for Whitening and Brightening Skin. (112957272A), CN Patent."},{"key":"ref_45","unstructured":"Chen, R., and Wu, T. (2021). Composition of Whitening Cream and Its Preparation Method. (112933020A), CN Patent."},{"key":"ref_46","unstructured":"Goo, B. (2021). Mask, Device, and Method for Whitening Skin. (20210030141A1), U.S. Patent."},{"key":"ref_47","unstructured":"Kong, Q., Chen, Q., Xia, G., and Mao, S. (2021). Composition Containing Alpha-Hydroxy Acid with Skin Whitening Effect and Preparation Method and Application Thereof. (113576933A), CN Patent."},{"key":"ref_48","unstructured":"Li, C. (2021). Preparation Method of Composite Freckle Removing and Whitening Composition. (112386552A), CN Patent."},{"key":"ref_49","unstructured":"Li, R., Chen, S., and Chen, L. (2021). Whitening Skin-Care Composition Comprising 4-Butylresorcinol, Nicotinamide and Resveratrol, and Its Preparation Method. (112675100A), CN Patent."},{"key":"ref_50","unstructured":"Luo, F., Niu, L., and Yang, M. (2021). Whitening Composition and Preparation Method. (112402316A), CN Patent."},{"key":"ref_51","unstructured":"Pan, J., Pan, Y., Liu, G., Huang, H., Huang, L., Li, Y., and Qiu, S. (2021). Composite Whitening Agent Lipid Carrier Containing Cream. (112516040A), CN Patent."},{"key":"ref_52","unstructured":"Qiu, J., Wang, X., and Pygmalion, M.-J. (2021). Cosmetic Composition for Brightening and\/or Whitening Skin Materials. (2021114024A1), WO Patent."},{"key":"ref_53","unstructured":"Wang, M. (2021). Whitening and Freckle Removing Essence and Its Preparation Method. (112587426A), CN Patent."},{"key":"ref_54","unstructured":"Wang, M. (2021). Whitening and Freckle-Removing Cream and Preparation Method. (112603869A), CN Patent."},{"key":"ref_55","unstructured":"Wang, Y., Guo, X., Mao, H., Xu, S., and Wang, J. (2021). Composition Containing Tranexamic Acid and Acetylchitosamine for Improving Skin Tone for Whitening Cosmetics. (112618400A), CN Patent."},{"key":"ref_56","unstructured":"Xie, K., Liu, H., Zhang, Y., Wu, C., and Tang, R. (2021). A Transparent Whitening Essence Containing 4-butyl Resorcinol and Preparation Method Thereof. (113081903A), CN Patent."},{"key":"ref_57","unstructured":"Zhou, Z., Hu, G., Li, C., Chen, Q., and Gong, S. (2021). Whitening Agent, Whitening Oil gel Containing the Same and Preparation Method Thereof. (112263496A), CN Patent."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cantelli, M., Ferrillo, M., Fabbrocini, G., and Granger, C. (2021). An Open-Label, Investigator-Initiated, Single-Center, Prospective, Pilot Clinical Study to Evaluate the Efficacy of a Skin Whitening serum applied twice daily combined with a spot-preventing SPF50+ sunscreen in healthy female subjects with melasma hyperpigmentation. J. Cosmet. Dermatol.","DOI":"10.1111\/jocd.14271"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/jdv.12051","article-title":"4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation","volume":"27","author":"Kolbe","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/jocd.12241","article-title":"Effects of topical application of B-Resorcinol and Glycyrrhetinic acid monotherapy and in combination with fractional CO2 laser treatment for benign hand hyperpigmentation treatment","volume":"15","author":"Grippaudo","year":"2016","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/jocd.13615","article-title":"Isobutylamido thiazolyl resorcinol for prevention of UVB-induced hyperpigmentation","volume":"20","author":"Vachiramon","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/ics.12626","article-title":"Thiamidol containing treatment regimens in facial hyperpigmentation: An international multi-centre approach consisting of a double-blind, controlled, split-face study and of an open-label, real-world study","volume":"42","author":"Riedel","year":"2020","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_63","unstructured":"Xu, J., and Zha, J. (2018). Method for Preparing 4-Alkyl Resorcin. (107805186A), CN Patent."},{"key":"ref_64","unstructured":"He, H., Jiang, C., and Dong, H. (2020). Organic Synthesis of 4-Alkyl-Resorcinol in Solvent-Free System. (109534961A), CN Patent."},{"key":"ref_65","unstructured":"Liu, Y., Yan, J., Zhang, M., and Hu, Y. (2020). Method for Preparing 4-Butyl-Resorcinol. (110903169A), CN Patent."},{"key":"ref_66","unstructured":"Zhang, K., and Zhang, T. (2020). One-Pot Method for Preparing 4-n-Butyl Resorcinol as Cosmetic Intermediate. (110803980A), CN Patent."},{"key":"ref_67","unstructured":"Tan, X., Zhang, Z., and Sun, X. (2019). Synthesis Method of 4-n-Butylresorcinol by Microchannel Reaction. (110511117A), CN Patent."},{"key":"ref_68","unstructured":"Xu, H., Fan, P., Qu, H., Tao, P., Shen, M., Wang, P., Ma, S., Shu, C., Shan, C., and Nie, W. (2020). Preparation of 4-Butylresorcinol. (111960924A), CN Patent."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.bmc.2014.01.032","article-title":"Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists","volume":"22","author":"Liu","year":"2014","journal-title":"Bioorg. Med. Chem."}],"container-title":["Applied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/2\/775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:28:56Z","timestamp":1760365736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/2\/775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":69,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["app12020775"],"URL":"https:\/\/doi.org\/10.3390\/app12020775","relation":{},"ISSN":["2076-3417"],"issn-type":[{"value":"2076-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}