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Targeted skin-lightening approaches inhibit tyrosinase, adjust melanogenic regulators, and strengthen antioxidant defenses. This study develops and standardizes an ursolic-acid–rich Annurca Apple Oleolite (AAO) extract, and evaluates both molecular effects and clinical outcomes. AAO shows strong tyrosinase inhibition, reduced melanin, altered TYRP-1, TYRP-2 and MITF expression, and improved skin brightness and tone uniformity in a randomized double-blind placebo-controlled trial.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/apple-oil-as-a-source-of-ursolic-acid-for-the-treatment-of-hyperpigmentary-disorders-with-molecular-and-clinical-evaluation/431466/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/apple-oil-as-a-source-of-ursolic-acid-for-the-treatment-of-hyperpigmentary-disorders-with-molecular-and-clinical-evaluation/431466.png","ImageObject",300,407,{"name":92,"@type":93},"Aditya","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address?","Question",{"text":112,"@type":113},"The study focuses on skin hyperpigmentation, an aesthetic and dermatological concern associated with increased melanin synthesis and oxidative stress.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is AAO and how was it evaluated?",{"text":117,"@type":113},"Annurca Apple Oleolite (AAO) is an apple oil extract rich in ursolic acid. It was standardized and assessed through molecular experiments and a randomized double-blind placebo-controlled clinical trial.",{"name":119,"@type":110,"acceptedAnswer":120},"What benefits did topical AAO show in the clinical trial?",{"text":121,"@type":113},"Topical AAO-containing formulation reduced UV and brown spot scores, decreased melanin index, and improved skin brightness and tone uniformity compared with placebo.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},431466,1790835296,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962085564549,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nApple oil as a source of ursolic acid for the treatment of hyperpigmentary disorders with molecular and clinical evaluation  \nMaria Maisto1, Vincenzo Piccolo1, Adua Marzocchi1, Lucia Ricci2, Benedetta Romano2, Daniela Claudia Maresca2, Ritamaria Di Lorenzo2􀀍, Sonia Laneri2, Giuseppe Ercolano2,3 & Angela Ianaro2,3  \nSkin hyperpigmentation represents a common aesthetic and dermatological concern, often resulting from excessive melanin synthesis and oxidative stress. Effective skin-lightening strategies target these processes by inhibiting tyrosinase activity, modulating melanogenic regulators, and enhancing antioxidant defenses. Ursolic acid, a natural triterpene abundant in apple peel, has shown potential as a safe and multifunctional skin-brightening molecule. In this study, an apple oil extract rich in ursolic acid (Annurca Apple Oleolite, AAO) was developed and standardized to 784.40 ± 7.58 µg/mL. The extract demonstrated significant tyrosinase inhibition and a marked reduction in melanin content inA375 melanoma cells, accompanied by downregulation of TYRP-1, TYRP-2, and MITF expression and modulation of oxidative stress markers. These molecular effects were confirmed in a randomized, double-blind, placebo-controlled clinical trial involving 42 subjects with hyperpigmented skin. Topical application of a formulation containing 2.5% AAOfor 28 days significantly reduced UV and brown spot scores (–6.4% and − 4.1%, respectively; p \u003C 0.001), decreased melanin index (–10.2%, p \u003C 0.001), and improved skin brightness and tone uniformity (ITA° +12.4%; L* +3.1%; both p \u003C 0.001) compared with placebo. Overall, the results highlight AAO as a promising natural agent for managing skin hyperpigmentation through multiple mechanisms, suggesting its potential utility in both cosmetic and dermatological formulations.  \nKeywords Ursolic acid, Hyperpigmentation, Melanogenesis, Skin wellness  \nAbbreviations  \nAA Annurca apple  \nAAO Annurca apple oil  \nCREB cAMP response element binding protein DCF 2’,7’-dichlorofluorescin  \nDMEM Dulbecco’s modified Eagle’s medium FLD Fluorescence detector  \nGCLC γ-glutamylcysteine ligase HMOX-1 Enzyme heme oxygenase ITA Individual typology angle KA Kojic acid  \nMI Melanin index  \nMITF Microphthalmia-associated transcription factor  \nOD Optical density  \nPGI Protected geographical indication ROS Reactive oxygen species  \nTYR Tyrosinase  \nTYRP Tyrosinase-related protein  \n1NutraPharmaLab, Department of Pharmacy, University of Naples Federico II, Naples, Italy. 2Dipartimentodi Farmacia , Università degli Studi di Napoli Federico II , Naples, Italy. 3Giuseppe Ercolano and Angela Ianaro contributed equally to this work. 􀀍 email: ritamaria.dilorenzo@unina. it  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nUA Ursolic acid  \nα-MSH Alpha-melanocyte-stimulating hormone  \nMelanin is the most important biological pigment in humans, responsible for the pigmentation of skin, eyes, and hair1. It is produced by melanocytes in specific sub-cellular lysosome-like structures called melanosomes. Physiologically, melanin synthesis and production protect human skin from UV radiation; however, its abnormal synthesis could lead to several skin disorders, including hyperpigmentation, melasma, and age spots. Specifically, melanogenesis is a multi-step process involving melanin synthesis and transport, and the subsequent release of melanosomes. Chemically, the melanogenesis process begins with the oxidation of tyrosine to dopaquinone, which is catalyzed by the enzyme tyrosinase. Subsequently, the dopaquinone is converted into dopachrome by an auto-oxidation reaction2. The L-Dopa produced is itself a tyrosinase substrate and is oxidized again todopaquinone, which undergoes further oxidative polymerization steps leading to the melanin formation3,4. Several molecular players are involved in regulating the melanogenesis process1. Specif","cbCaitCGEipR6IG5","https://ap.wps.com/l/cbCaitCGEipR6IG5","pdf",2350721,13,"English","# Background and rationale\n## Role of melanogenesis and tyrosinase\n## Oxidative stress and antioxidant defenses\n## Need for dual-action natural compounds\n# Study focus and key outcomes","[{\"question\":\"What problem does the study address?\",\"answer\":\"The study focuses on skin hyperpigmentation, an aesthetic and dermatological concern associated with increased melanin synthesis and oxidative stress.\"},{\"question\":\"What is AAO and how was it evaluated?\",\"answer\":\"Annurca Apple Oleolite (AAO) is an apple oil extract rich in ursolic acid. It was standardized and assessed through molecular experiments and a randomized double-blind placebo-controlled clinical trial.\"},{\"question\":\"What benefits did topical AAO show in the clinical trial?\",\"answer\":\"Topical AAO-containing formulation reduced UV and brown spot scores, decreased melanin index, and improved skin brightness and tone uniformity compared with placebo.\"}]","Apple oil as a source of ursolic acid for the treatment of hyperpigmentary disorders - with molecular and clinical evaluation | PDF",1790655584,33]