{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T07:39:00Z","timestamp":1794555540502,"version":"4.9.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Genencell Co. Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of <jats:italic>Elaeocarpus sylvestris <\/jats:italic>var.<jats:italic> ellipticus<\/jats:italic>), a novel inhibitor of varicella zoster virus reactivation in healthy adults.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (<jats:italic>n<\/jats:italic>\u2009=\u200932), subjects randomly received a single oral dose of 240, 480, 960, or 1440\u00a0mg ES16001 or a placebo. In the MAD study (<jats:italic>n<\/jats:italic>\u2009=\u200916), subjects randomly received once daily doses of 480 or 960\u00a0mg ES16001 or a placebo for 5\u00a0days. The safety and tolerability of the drug were evaluated by monitoring participants\u2019 treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic>: CRIS, KCT0006066. Registered 7 April 2021\u2014Retrospectively registered, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/cris.nih.go.kr\/cris\/search\/detailSearch.do\/19071\">https:\/\/cris.nih.go.kr\/cris\/search\/detailSearch.do\/19071<\/jats:ext-link>).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40001-021-00565-z","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T07:07:15Z","timestamp":1628752035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, tolerability of ES16001, a novel varicella zoster virus reactivation inhibitor, in healthy adults"],"prefix":"10.1186","volume":"26","clinical-trial-number":[{"clinical-trial-number":"kct0006066","registry":"10.18810\/cris"}],"author":[{"given":"Jeon","family":"Hwang-Bo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungwook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Won","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Geun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Yong","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-2237","authenticated-orcid":false,"given":"Se Chan","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"565_CR1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.2217\/fvl.10.90","volume":"6","author":"E Eshleman","year":"2011","unstructured":"Eshleman E, Shahzad A, Cohrs RJ. Varicella zoster virus latency. Future Virol. 2011;6:341\u201355.","journal-title":"Future Virol"},{"key":"565_CR2","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1212\/WNL.45.12_Suppl_8.S41","volume":"45","author":"MN Oxman","year":"1995","unstructured":"Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology. 1995;45:S41.","journal-title":"Neurology"},{"key":"565_CR3","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.3346\/jkms.2019.34.e1","volume":"34","author":"YJ Kim","year":"2019","unstructured":"Kim YJ, Lee CN, Lee MS, Lee JH, Lee JY, Han K, Park YM. Recurrence rate of herpes zoster and its risk factors: a population-based cohort study. J Korean Med Sci. 2019;34:e1.","journal-title":"J Korean Med Sci"},{"key":"565_CR4","doi-asserted-by":"publisher","first-page":"922","DOI":"10.7326\/0003-4819-130-11-199906010-00017","volume":"130","author":"JI Cohen","year":"1999","unstructured":"Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella zoster virus infection. Ann Intern Med. 1999;130:922\u201332.","journal-title":"Ann Intern Med"},{"key":"565_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3389\/fmicb.2020.00139","volume":"11","author":"DM \u00c1lvarez","year":"2020","unstructured":"\u00c1lvarez DM, Castillo E, Duarte LF, et al. Current antivirals and novel botanical molecules interfering with herpes simplex virus infection. Front Microbiol. 2020;11:139.","journal-title":"Front Microbiol"},{"key":"565_CR6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1053\/spid.2002.29753","volume":"13","author":"AM Arvin","year":"2002","unstructured":"Arvin AM. Antiviral therapy for varicella and herpes zoster. Semin Pediatr Infect Dis. 2002;13:12\u201321.","journal-title":"Semin Pediatr Infect Dis"},{"key":"565_CR7","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0166-3542(98)00057-6","volume":"40","author":"M Ida","year":"1999","unstructured":"Ida M, Kageyama S, Sato H, Kamiyama T, Yamamura J, Kurokawa M, Morohashi M, Shiraki K. Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants. Antivir Res. 1999;40:155\u201366.","journal-title":"Antivir Res"},{"key":"565_CR8","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s10265-013-0571-5","volume":"126","author":"K Sugai","year":"2013","unstructured":"Sugai K, Setsuko S, Nagamitsu T, Murakami N, Kato H, Yoshimaru H. Genetic differentiation in Elaeocarpus photiniifolia (Elaeocarpaceae) associated with geographic distribution and habitat variation in the Bonin (Ogasawara) Islands. J Plant Res. 2013;126:763\u201374.","journal-title":"J Plant Res"},{"key":"565_CR9","first-page":"865","volume":"45","author":"J Li","year":"2016","unstructured":"Li J, Huang WL, Zhou TT, Xue L. Physiological characteristics of Elaeocarpus sylvestris seedlings under different densities of plants. Bangl J Bot. 2016;45:865\u201372.","journal-title":"Bangl J Bot"},{"key":"565_CR10","doi-asserted-by":"publisher","first-page":"744","DOI":"10.3892\/mmr.2013.1824","volume":"9","author":"KP To","year":"2014","unstructured":"To KP, Kang SC, Song YJ. The extract of Elaeocarpus sylvestris inhibits human cytomegalovirus immediate early gene expression and replication in vitro. Mol Med Rep. 2014;9:744\u20138.","journal-title":"Mol Med Rep"},{"key":"565_CR11","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1002\/ptr.2430","volume":"22","author":"E Park","year":"2008","unstructured":"Park E, Lee NH, Baik JS, Jee Y. Elaeocarpus sylvestris modulates gamma ray-induced immunosuppression in mice: implications in radioprotection. Phytother Res. 2008;22:1046\u201351.","journal-title":"Phytother Res"},{"key":"565_CR12","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.3923\/pjbs.2014.1106.1114","volume":"17","author":"AI Prihantini","year":"2014","unstructured":"Prihantini AI, Tachibana S, Itoh K. Evaluation of antioxidant and alpha-glucosidase inhibitory activities of some subtropical plants. Pak J Biol Sci. 2014;17:1106\u201314.","journal-title":"Pak J Biol Sci"},{"key":"565_CR13","unstructured":"Kang SC, Park DW, \u201cPharmaceutical composition for preventing and treating alpha herpes virus infection, containing, as active ingredient, Elaeocarpus sylvestris extract or fraction thereof\u201d PCT\/KR2017\/004614, April, 28, 2017."},{"issue":"2","key":"565_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","volume":"7","author":"AB Nair","year":"2016","unstructured":"Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27\u201331.","journal-title":"J Basic Clin Pharm"}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-021-00565-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-021-00565-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-021-00565-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T07:22:10Z","timestamp":1628752930000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-021-00565-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["565"],"URL":"https:\/\/doi.org\/10.1186\/s40001-021-00565-z","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]},"assertion":[{"value":"16 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This clinical trial (GNC_PT1_2018001) was reviewed and approved by the Ethics Committee of Seoul National University Bundang Hospital, and was performed in accordance with Korean Good Clinical Practice (KGCP). This study is based on the Helsinki Declaration and was conducted with the rights and welfare of the subjects in mind. Prior to screening, all participants provided written informed consent to participate in the study after having been informed about the nature and purpose of the study and participation\/withdrawal conditions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"92"}}