{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:39:51Z","timestamp":1791841191562,"version":"4.3.4"},"reference-count":70,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development (AMED)","award":["22fk0108123h1603"],"award-info":[{"award-number":["22fk0108123h1603"]}]},{"name":"Japan Agency for Medical Research and Development (AMED)","award":["22wm0225018s0503"],"award-info":[{"award-number":["22wm0225018s0503"]}]},{"name":"Japan Agency for Medical Research and Development (AMED)","award":["22wm0125006h0001"],"award-info":[{"award-number":["22wm0125006h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Currently, there are no specific therapeutics for flavivirus infections, including dengue virus (DENV) and Zika virus (ZIKV). In this study, we evaluated extracts from the plants Hedyotis diffusa (HD) and Artemisia capillaris (AC) to determine the antiviral activity against DENV, ZIKV, and Japanese encephalitis virus (JEV). HD and AC demonstrated inhibitory activity against JEV, ZIKV, and DENV replication and reduced viral RNA levels in a dose\u2013responsive manner, with non-cytotoxic concentration ranging from 0.1 to 10 mg\/mL. HD and AC had low cytotoxicity to Vero cells, with CC50 values of 33.7 \u00b1 1.6 and 30.3 \u00b1 1.7 mg\/mL (mean \u00b1 SD), respectively. The anti-flavivirus activity of HD and AC was also consistent in human cell lines, including human glioblastoma (T98G), human chronic myeloid leukemia (K562), and human embryonic kidney (HEK-293T) cells. Viral-infected, HD-treated cells demonstrated downregulation of cytokines including CCR1, CCL26, CCL15, CCL5, IL21, and IL17C. In contrast, CCR1, CCL26, and AIMP1 were elevated following AC treatment in viral-infected cells. Overall, HD and AC plant extracts demonstrated flavivirus replication inhibitory activity, and together with immunoregulatory cytokine signatures, these results suggest that HD and AC possess bioactive compounds that may further be refined as promising candidates for clinical applications.<\/jats:p>","DOI":"10.3390\/plants11192589","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T01:21:07Z","timestamp":1665364867000},"page":"2589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Antiviral Efficacy of Hedyotis diffusa and Artemisia capillaris Extracts against Dengue Virus, Japanese Encephalitis Virus, and Zika Virus Infection and Immunoregulatory Cytokine Signatures"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-353X","authenticated-orcid":false,"given":"Zhan Qiu","family":"Mao","sequence":"first","affiliation":[{"name":"Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Minakawa","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-6659","authenticated-orcid":false,"given":"Meng Ling","family":"Moi","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tibs.2020.12.007","article-title":"Molecular Determinants of Flavivirus Virion Assembly","volume":"46","author":"Barnard","year":"2021","journal-title":"Trends Biochem. 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