{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:45:49Z","timestamp":1791805549610,"version":"4.3.4"},"reference-count":61,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAPES"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mem. Inst. Oswaldo Cruz"],"abstract":"<jats:p>BACKGROUND Herpes Simplex Virus (HSV) infection represents a global health concern with a significant impact on affected individuals\u2019 quality of life. Conventional treatment relies on nucleoside analogues such as acyclovir, which, although effective, have limitations including viral resistance and low bioavailability. In this context, natural products such as resveratrol (RSV) and \u03b2-caryophyllene (BCP) emerge as promising alternatives due to their antiviral and immunomodulatory properties. However, these compounds present challenges related to stability and solubility, necessitating the use of controlled drug delivery systems such as nanoemulsions.  OBJECTIVES This study aimed to develop and characterise nanoemulsions containing RSV and BCP, either individually or in combination, for the treatment of HSV type 1 (HSV-1) infections.  METHODS The nanoemulsions were prepared using a low-energy spontaneous emulsification technique and characterised for particle size, polydispersity index (PDI), and zeta potential. The antiviral activity, cytotoxicity, and wound-healing potential of the nanoemulsions were evaluated in vitro using VERO and human gingival fibroblast (HGF) cells.  FINDINGS Results showed that RSV exhibited significant antiviral activity against HSV-1, while BCP demonstrated moderate activity. Nanoencapsulation improved the biocompatibility of RSV but increased the cytotoxicity of BCP. The combination of RSV and BCP in nanoemulsions showed enhanced antiviral activity, with inhibition percentages above 70%. However, the nanoemulsions did not significantly promote wound healing in HGF cells. Additionally, the nanoemulsions did not protect against Ultraviolet Crosslinker (UVC)-induced cell damage.  MAIN CONCLUSIONS Nanoemulsions containing RSV and BCP demonstrated enhanced antiviral activity against HSV-1, particularly when combined, suggesting a synergistic effect between both compounds. Nanoencapsulation improved the biocompatibility of RSV but increased the cytotoxicity of BCP. Although no significant effects were observed in wound healing or UV protection assays, the results support nanoemulsions as a promising platform for improving the antiviral performance of these compounds for topical HSV-1 treatment.<\/jats:p>","DOI":"10.1590\/0074-02760250333","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:58:28Z","timestamp":1791802708000},"source":"Crossref","is-referenced-by-count":0,"title":["Nanoemulsions loaded with \u00df-caryophyllene and resveratrol for herpes infections"],"prefix":"10.1590","volume":"121","author":[{"given":"Isabella Dai","family":"Pr\u00e1","sequence":"first","affiliation":[{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]},{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Santos","family":"Porto","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Costa Bernardo","family":"Port","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edse Gauer","family":"Schulte","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]},{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora Fretes","family":"Argenta","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina","place":["Florian\u00f3polis, SC, 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ciliary ganglia independently from sensory trigeminal ganglia to cause recurrent ocular disease","volume":"89","author":"Lee S","year":"2015","journal-title":"J Virol"},{"issue":"Suppl. 1","key":"ref3","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1086\/505359","article-title":"The cycle of human herpes simplex virus infection: virus transport and immune control","volume":"194","author":"Cunningham AL","year":"2006","journal-title":"J Infect Dis"},{"issue":"5","key":"ref4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: global infection prevalence and incidence estimates, 2016","volume":"98","author":"James C","year":"2020","journal-title":"Bull World Health Organ"},{"issue":"10","key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0140765","article-title":"Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 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JJ","year":"1999","journal-title":"Antiviral Res"},{"key":"ref41","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155476","article-title":"Effect of resveratrol on herpesvirus encephalitis: evidences for its mechanisms of action","volume":"127","author":"Huang Z","year":"2024","journal-title":"Phytomedicine"},{"key":"ref42","doi-asserted-by":"crossref","DOI":"10.1177\/13596535241271589","article-title":"Antiviral potential of phenolic compounds against HSV-1: in vitro study","volume":"29","author":"Zangooie S","year":"2024","journal-title":"Antivir Ther"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.virusres.2015.05.015","article-title":"Nutraceutical activators of AMPK\/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection","volume":"205","author":"Leyton L","year":"2015","journal-title":"Virus Res"},{"issue":"7","key":"ref44","doi-asserted-by":"crossref","first-page":"11808","DOI":"10.3390\/molecules200711808","article-title":"The anticancer, antioxidant and antimicrobial properties of the sesquiterpene \u03b2-caryophyllene from the essential oil of Aquilaria crassna","volume":"20","author":"Dahham SS","year":"2015","journal-title":"Molecules"},{"issue":"9","key":"ref45","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.phymed.2008.04.018","article-title":"Melissa officinalis oil affects infectivity of enveloped herpesviruses","volume":"15","author":"Schnitzler P","year":"2008","journal-title":"Phytomedicine"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1600-0714.2007.00586.x","article-title":"Herpes simplex virus type 1 infection: overview on relevant clinico-pathological features","volume":"37","author":"Arduino PG","year":"2008","journal-title":"J Oral Pathol Med"},{"issue":"4","key":"ref47","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1568-1637(02)00024-7","article-title":"UV-light-induced signal cascades and skin aging","volume":"1","author":"Ritti\u00e9 L","year":"2002","journal-title":"Ageing Res Rev"},{"issue":"3","key":"ref48","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.bcp.2014.09.002","article-title":"Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway","volume":"92","author":"Bai Y","year":"2014","journal-title":"Biochem Pharmacol"},{"key":"ref49","doi-asserted-by":"crossref","DOI":"10.1038\/srep16386","article-title":"Resveratrol inhibits epithelial-mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy","volume":"5","author":"Ishikawa K","year":"2015","journal-title":"Sci 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