Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos
Plumbagin (PL; 5-hydroxy-2-methyl-1,4-naphthoquinone) is an analogue of juglone (JG) with additional methylation on carbon 2. It has been found in fungi, insects, and plants, especially Malaysian persimmons, and plants containing PL are globally used as folk medicines. Among 1,4-naphthoquinones test...
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325008802 |
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| author | Yeonju Lim Chaeeun Kim Donghyeon Kim Myoung-Jin Kim Ji-Woo Yu Min-Ho Song Yurim Kim Junhee Son Ji-Ho Lee Sung-Eun Lee |
| author_facet | Yeonju Lim Chaeeun Kim Donghyeon Kim Myoung-Jin Kim Ji-Woo Yu Min-Ho Song Yurim Kim Junhee Son Ji-Ho Lee Sung-Eun Lee |
| author_sort | Yeonju Lim |
| collection | DOAJ |
| description | Plumbagin (PL; 5-hydroxy-2-methyl-1,4-naphthoquinone) is an analogue of juglone (JG) with additional methylation on carbon 2. It has been found in fungi, insects, and plants, especially Malaysian persimmons, and plants containing PL are globally used as folk medicines. Among 1,4-naphthoquinones tested in this study, PL and JG exhibited high lethality towards zebrafish (Danio rerio) embryos and reduced their hatchability, and induced morphological changes. In addition, zebrafish embryos exposed to 0.13 µM of PL at 4 h post-fertilization exhibited severely reduced brain differentiation in a PL concentration-dependent manner, resulting in severe cyclopia symptoms, with individuals experiencing cyclopia ultimately dying. The cyclopia induced by PL was more severe than that of the positive controls, ethanol, forskolin, and cyclopamine. Increased apoptosis and reactive oxygen species (ROS) generation were associated with PL-induced cyclopia, and concurrent treatments with ROS-quenching curcuminoids decreased cyclopia. Metabolomic activity in PL-treated embryos was also severely disrupted, and even surviving individuals would likely not retain proper function. Thus, plants should be monitored for the presence of PL, given its strong cyclopia-inducing effects on animals. Due to the high frequency and severity of symptomatic zebrafish embryos in this study, PL’s association with holoprosencephaly, specifically cyclopia, is undeniable. |
| format | Article |
| id | doaj-art-dbabc11caa984dd8ad3e1b23d2538538 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-dbabc11caa984dd8ad3e1b23d25385382025-08-20T03:04:06ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211853510.1016/j.ecoenv.2025.118535Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryosYeonju Lim0Chaeeun Kim1Donghyeon Kim2Myoung-Jin Kim3Ji-Woo Yu4Min-Ho Song5Yurim Kim6Junhee Son7Ji-Ho Lee8Sung-Eun Lee9Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaResearch Planning & Management Division, Nakdonggang National Institute of Biological Resources, Sangju, Gyeongbuk State 37242, Republic of KoreaDepartment of Crop Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of KoreaDepartment of Crop Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of KoreaSchool of Natural Resources and Environmental Science, Department of Biological Environment, Kangwon National University, Chuncheon, Gangwon State 24341, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea; Corresponding author at: Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea.Plumbagin (PL; 5-hydroxy-2-methyl-1,4-naphthoquinone) is an analogue of juglone (JG) with additional methylation on carbon 2. It has been found in fungi, insects, and plants, especially Malaysian persimmons, and plants containing PL are globally used as folk medicines. Among 1,4-naphthoquinones tested in this study, PL and JG exhibited high lethality towards zebrafish (Danio rerio) embryos and reduced their hatchability, and induced morphological changes. In addition, zebrafish embryos exposed to 0.13 µM of PL at 4 h post-fertilization exhibited severely reduced brain differentiation in a PL concentration-dependent manner, resulting in severe cyclopia symptoms, with individuals experiencing cyclopia ultimately dying. The cyclopia induced by PL was more severe than that of the positive controls, ethanol, forskolin, and cyclopamine. Increased apoptosis and reactive oxygen species (ROS) generation were associated with PL-induced cyclopia, and concurrent treatments with ROS-quenching curcuminoids decreased cyclopia. Metabolomic activity in PL-treated embryos was also severely disrupted, and even surviving individuals would likely not retain proper function. Thus, plants should be monitored for the presence of PL, given its strong cyclopia-inducing effects on animals. Due to the high frequency and severity of symptomatic zebrafish embryos in this study, PL’s association with holoprosencephaly, specifically cyclopia, is undeniable.http://www.sciencedirect.com/science/article/pii/S01476513250088021,4-NaphthoquinonesPlumbaginCyclopiaZebrafish embryosApoptosisROS generation |
| spellingShingle | Yeonju Lim Chaeeun Kim Donghyeon Kim Myoung-Jin Kim Ji-Woo Yu Min-Ho Song Yurim Kim Junhee Son Ji-Ho Lee Sung-Eun Lee Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos Ecotoxicology and Environmental Safety 1,4-Naphthoquinones Plumbagin Cyclopia Zebrafish embryos Apoptosis ROS generation |
| title | Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos |
| title_full | Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos |
| title_fullStr | Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos |
| title_full_unstemmed | Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos |
| title_short | Plumbagin, a natural derivative of 1,4-naphthoquinone, induces cyclopic phenomenon via increased apoptosis and ROS generation in the early stage of zebrafish embryos |
| title_sort | plumbagin a natural derivative of 1 4 naphthoquinone induces cyclopic phenomenon via increased apoptosis and ros generation in the early stage of zebrafish embryos |
| topic | 1,4-Naphthoquinones Plumbagin Cyclopia Zebrafish embryos Apoptosis ROS generation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325008802 |
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