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This review assesses topical effectiveness, molecular mechanisms, and advanced formulation strategies for UA enantiomers and UA-rich extracts. Literature spanning PubMed, Scopus, and Google Scholar identified 36 studies on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro findings show apoptosis induction in resistant melanoma via extrinsic and intrinsic pathways, while non-cancer models demonstrate accelerated wound and burn repair through VEGF upregulation, fibroblast proliferation, and extracellular matrix remodeling, including reduced hypertrophic scarring. Drug delivery systems such as liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds enhance skin permeability and localized retention, supporting safer topical translation.",{"@graph":69,"@context":123},[70,84,106],{"@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/usnic-acid-and-its-topical-use-a-concise-review/349371/",{"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/usnic-acid-and-its-topical-use-a-concise-review/349371.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main therapeutic rationale for using usnic acid topically?","Question",{"text":113,"@type":114},"Although usnic acid has notable biological activities, its internal use is restricted by documented systemic hepatotoxicity. Topical administration is proposed to shift its potential toward dermatological applications while limiting systemic risks.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do UA enantiomers differ in biological and allergic effects?",{"text":118,"@type":114},"UA exists as two enantiomers, (+)-UA and (−)-UA. Reports indicate immunological differences, with the dextrorotatory (+)-UA showing stronger allergenic potency than (−)-UA.",{"name":120,"@type":111,"acceptedAnswer":121},"Which topical delivery approaches are discussed to improve safety and effectiveness?",{"text":122,"@type":114},"The review describes advanced drug delivery systems including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds. These approaches aim to enhance skin permeability and localized dermal retention while mitigating sensitization and systemic concerns.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},349371,1790463252,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"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},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Review  \nUsnic Acid and Its Topical Use—A Concise Review  \nGabriela Siedlarczyk 1,2, Irma Podolak 2 and Agnieszka Galanty 2, *  \nAcademic Editor: Ericsson Coy-Barrera Received: 31 May 2026  \nRevised: 15 June 2026  \nAccepted: 19 June 2026  \nPublished: 22 June 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 16 Łazarza Str., 31-530 Cracow, Poland; [gabriela.siedlarczyk@doctoral.uj.edu.pl](gabriela.siedlarczyk@doctoral.uj.edu.pl)  \n2 Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland; [irma.podolak@uj.edu.pl](irma.podolak@uj.edu.pl)  \n* Correspondence: [agnieszka.galanty@uj.edu.pl](agnieszka.galanty@uj.edu.pl)  \nAbstract  \nUsnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UArich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care.  \nKeywords: usnic acid; lichen extracts; melanoma; wound healing; liposomes; topical  \n1. Introduction  \nLichens (Latin Lichenes) or lichenized fungi are symbiotic organisms composed of an algal and/or a cyanobacterial and a fungal unit, accompanied by some bacterial communities [1] . Such coexistence results in the production of structurally unique and potentially biologically active compounds, among which the secondary metabolite UA remains one of the most intriguing. It was first isolated in 1844 by the German scientist Knop from some Usnea species, after which the compound was named. Usnic acid exists as a chiral molecule in two enantiomers (Figure 1): dextrorotatory (+)-UA and levorotatory (−)-UA [2] . UA is widely distributed across various lichen genera, including Usnea, Parmelia, Lecanora, Cladonia, Ramalina, Alectoria, and Evernia, while some genera did not produce the compound [3] . The compound is of lipophilic nature, which results in its poor water solubility; thus, it is most often extracted from the lichen matrix with chloroform, ethyl acetate, or acetone [4] .  \nFigure 1. Chemical structures of usnic acid (UA) enantiomers: (+)-usnic acid and (−)-usnic acid.  \nThe UA enantiomers exhibit a broad spectrum of biological activities, encompassing cytotoxic, antimicrobial, anti-inflammatory, and photoprotective properties [3] . Despite the extensive documentation of these biological traits, comparative data regarding the specific activities of the two enantiomers remain remarkably limited. The vast majority of published studie","cbCaiqJklQw0OQeT","https://ap.wps.com/l/cbCaiqJklQw0OQeT","pdf",5550327,"English","# Abstract\n# Introduction\n## Lichen-derived usnic acid and enantiomers\n## Biological activities and research gaps\n## Systemic hepatotoxicity and rationale for topical use\n## Allergic contact dermatitis and sensitization risk\n# Advanced formulation strategies\n## Topical efficacy and mechanisms\n## Drug delivery systems","[{\"question\":\"What is the main therapeutic rationale for using usnic acid topically?\",\"answer\":\"Although usnic acid has notable biological activities, its internal use is restricted by documented systemic hepatotoxicity. Topical administration is proposed to shift its potential toward dermatological applications while limiting systemic risks.\"},{\"question\":\"How do UA enantiomers differ in biological and allergic effects?\",\"answer\":\"UA exists as two enantiomers, (+)-UA and (−)-UA. Reports indicate immunological differences, with the dextrorotatory (+)-UA showing stronger allergenic potency than (−)-UA.\"},{\"question\":\"Which topical delivery approaches are discussed to improve safety and effectiveness?\",\"answer\":\"The review describes advanced drug delivery systems including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds. These approaches aim to enhance skin permeability and localized dermal retention while mitigating sensitization and systemic concerns.\"}]","Usnic Acid and Its Topical Use - A Concise Review | PDF",1790083065,48]